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    Clinical Trial Results:
    A prospective Randomised, open label, blinded endpoint (PROBE) study to Evaluate DUAL antithrombotic therapy with dabigatran etexilate (110mg and 150mg b.i.d.) plus clopidogrel or ticagrelor vs. triple therapy strategy with warfarin (INR 2.0 – 3.0) plus clopidogrel or ticagrelor and aspirin in patients with non valvular atrial fibrillation (NVAF) that have undergone a percutaneous coronary intervention (PCI) with stenting (RE-DUAL PCI)

    Summary
    EudraCT number
    		 2013-003201-26
    Trial protocol
    		 SE   DK   GR   DE   PT   HU   ES   FI   NL   CZ   AT   IT   BE   IE   SK   SI   GB   BG   HR   PL   FR  
    Global end of trial date
    05 Jun 2017

    Results information
    Results version number
    		 v2(current)
    This version publication date
    13 Dec 2021
    First version publication date
    21 Jun 2018
    Other versions
    		 v1
    Version creation reason

    Trial information

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    Trial identification
    Sponsor protocol code
    1160.186
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02164864
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Boehringer Ingelheim
    Sponsor organisation address
    173 Binger Strasse, Ingelheim am Rhein, Germany, 55216
    Public contact
    QRPE Processes and Systems Coordination Clinical Trial Information Disclosure, Boehringer Ingelheim, 001 8002430127, clintriage.rdg@boehringer-ingelheim.com
    Scientific contact
    QRPE Processes and Systems Coordination Clinical Trial Information Disclosure, Boehringer Ingelheim, 001 8002430127, clintriage.rdg@boehringer-ingelheim.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    12 Jul 2017
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    05 Jun 2017
    Global end of trial reached?
    Yes
    Global end of trial date
    05 Jun 2017
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The main objective of the trial was to compare a dual antithrombotic regimen of 110 mg dabigatran etexilate (DE 110) twice daily plus clopidogrel or ticagrelor (110 mg DE-DAT) and 150 mg dabigatran etexilate (DE 150) twice daily plus clopidogrel or ticagrelor (150 mg DE-DAT) with a triple antithrombotic therapy (TAT) of warfarin plus clopidogrel or ticagrelor plus aspirin (warfarin-TAT) in patients with non-valvular atrial fibrillation (NVAF) that underwent a percutaneous coronary intervention (PCI) with stenting.
    Protection of trial subjects
    Only subjects that met all the study inclusion and none of the exclusion criteria were entered in the study. All subjects were free to withdraw from the clinical trial at any time for any reason given. Close monitoring of all subjects was adhered to throughout the trial conduct.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    06 Aug 2014
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Argentina: 52
    Country: Number of subjects enrolled
    Australia: 31
    Country: Number of subjects enrolled
    Austria: 19
    Country: Number of subjects enrolled
    Belgium: 47
    Country: Number of subjects enrolled
    Brazil: 34
    Country: Number of subjects enrolled
    Bulgaria: 77
    Country: Number of subjects enrolled
    Canada: 56
    Country: Number of subjects enrolled
    Chile: 13
    Country: Number of subjects enrolled
    Colombia: 12
    Country: Number of subjects enrolled
    Croatia: 41
    Country: Number of subjects enrolled
    Czechia: 50
    Country: Number of subjects enrolled
    Denmark: 61
    Country: Number of subjects enrolled
    Finland: 45
    Country: Number of subjects enrolled
    France: 102
    Country: Number of subjects enrolled
    Germany: 486
    Country: Number of subjects enrolled
    Greece: 101
    Country: Number of subjects enrolled
    Hong Kong: 17
    Country: Number of subjects enrolled
    Hungary: 119
    Country: Number of subjects enrolled
    India: 35
    Country: Number of subjects enrolled
    Ireland: 15
    Country: Number of subjects enrolled
    Israel: 37
    Country: Number of subjects enrolled
    Italy: 91
    Country: Number of subjects enrolled
    Japan: 117
    Country: Number of subjects enrolled
    Korea, Republic of: 85
    Country: Number of subjects enrolled
    Mexico: 12
    Country: Number of subjects enrolled
    Netherlands: 55
    Country: Number of subjects enrolled
    New Zealand: 5
    Country: Number of subjects enrolled
    Norway: 62
    Country: Number of subjects enrolled
    Poland: 99
    Country: Number of subjects enrolled
    Portugal: 45
    Country: Number of subjects enrolled
    Russian Federation: 131
    Country: Number of subjects enrolled
    Singapore: 9
    Country: Number of subjects enrolled
    Slovakia: 40
    Country: Number of subjects enrolled
    Slovenia: 16
    Country: Number of subjects enrolled
    Spain: 121
    Country: Number of subjects enrolled
    Sweden: 47
    Country: Number of subjects enrolled
    Taiwan: 37
    Country: Number of subjects enrolled
    Thailand: 30
    Country: Number of subjects enrolled
    Turkey: 168
    Country: Number of subjects enrolled
    United Kingdom: 69
    Country: Number of subjects enrolled
    United States: 156
    Worldwide total number of subjects
    2845
    EEA total number of subjects
    1739
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    652
    From 65 to 84 years
    2089
    85 years and over
    104

    Subject disposition

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    Recruitment
    Recruitment details
    		 Patients aged ≥80 years in the United States of America (USA) were assigned to 110 milligram (mg) Dual antithrombotic therapy with dabigatran etexilate (DE-DAT), 150 mg DE-DAT, or warfarin. All other patients aged ≥80 years (for Japan ≥70 years) outside of the USA were assigned to 110 mg DE-DAT or warfarin.

    Pre-assignment
    Screening details
    		 All patients (Pts) were screened for eligibility to participate in trial. Pts attended specialist sites to ensure that they met all implemented inclusion/exclusion criteria. Pts were not to be randomised to trial drug if any of specific entry criteria was violated. In this study, 2725 Pts were entered & randomised. 2678 Pts were treated.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded
    Blinding implementation details
    A prospective Randomised, open label, blinded endpoint (PROBE) study.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Dabigatran Etexilate 110mg
    Arm description
    		 Patients were orally administered Dabigatran Etexilate 110mg capsule twice daily (BID) for at least 6 months.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Dabigatran Etexilate
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Patients were orally administered Dabigatran Etexilate 110mg capsule twice daily (BID) for at least 6 months.

    Arm title
    		 Dabigatran Etexilate 150mg
    Arm description
    		 Patients were orally administered Dabigatran Etexilate 150mg capsule twice daily (BID) for at least 6 months.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Dabigatran Etexilate
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Patients were orally administered Dabigatran Etexilate 150mg capsule twice daily (BID) for at least 6 months.

    Arm title
    		 Warfarin
    Arm description
    		 Patients were orally administered warfarin 1 mg, 3 mg, or 5 mg tablets once daily for at least 6 months. The warfarin dose was titrated as needed to maintain the target International normalised ratio (INR) of 2.0 to 3.0 (2.0 to 2.6 for Japanese patients aged ≥70 years); 2.0 to 2.5 if feasible
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Warfarin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Patients were orally administered warfarin 1 mg, 3 mg, or 5 mg tablets once daily for at least 6 months. The warfarin dose was titrated as needed to maintain the target International normalised ratio (INR) of 2.0 to 3.0 (2.0 to 2.6 for Japanese patients aged ≥70 years); 2.0 to 2.5 if feasible

    Number of subjects in period 1 [1]
    		Dabigatran Etexilate 110mg Dabigatran Etexilate 150mg Warfarin
    Started
    981
    763
    981
    Completed
    886
    703
    849
    Not completed
    95
    60
    132
         Fatal
    55
    31
    51
         Non-Fatal
    10
    10
    8
         Consent withdrawn, not due to AE
    21
    8
    56
         Lost to follow-up
    4
    3
    2
         Other than stated
    3
    4
    14
         Protocol deviation
    2
    4
    1
    Notes
    [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
    Justification: Justification: Baseline characteristics are based on patients who were randomised after successfully completing the screening period and received at least one of the trial medication. No Statistical analysis

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Dabigatran Etexilate 110mg
    Reporting group description
    		 Patients were orally administered Dabigatran Etexilate 110mg capsule twice daily (BID) for at least 6 months.

    Reporting group title
    Dabigatran Etexilate 150mg
    Reporting group description
    		 Patients were orally administered Dabigatran Etexilate 150mg capsule twice daily (BID) for at least 6 months.

    Reporting group title
    Warfarin
    Reporting group description
    		 Patients were orally administered warfarin 1 mg, 3 mg, or 5 mg tablets once daily for at least 6 months. The warfarin dose was titrated as needed to maintain the target International normalised ratio (INR) of 2.0 to 3.0 (2.0 to 2.6 for Japanese patients aged ≥70 years); 2.0 to 2.5 if feasible

    Reporting group values
    		 Dabigatran Etexilate 110mg Dabigatran Etexilate 150mg Warfarin Total
    Number of subjects
    		 981 763 981 2725
    Age categorical
    Units: Subjects
    Age Continuous
    Full analysis set (FAS): All consenting patients randomised were analysed in the treatment group to which they were randomised regardless of whether they took trial medication. The start date of the observation period for this analysis set was the date of randomisation. Patients who discontinued trial medication were followed until the end of the trial. Patients who were lost to follow-up for vital status were censored for the primary endpoint at the time of their last known vital status.
    Units: years
        arithmetic mean (standard deviation)
    		 71.5 ( 8.87 ) 68.6 ( 7.65 ) 71.7 ( 8.90 ) -
    Sex: Female, Male
    Number of subjects is categorized as Male or Female
    Units: Subjects
        Female
    		 253 171 231 655
        Male
    		 728 592 750 2070
    Race/Ethnicity, Customized
    The details on Race has been provided
    Units: Subjects
        Asian
    		 116 79 125 320
        Black
    		 5 7 3 15
        White
    		 851 658 835 2344
        Other
    		 5 8 7 20
        Missing
    		 4 11 11 26
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    		 70 46 59 175
        Not Hispanic or Latino
    		 903 700 904 2507
        Unknown or Not Reported
    		 8 17 18 43
    Age, Customized
    Units: Subjects
        <80: EU/ROW
    		 725 699 718 2142
        <80: USA
    		 54 53 61 168
        ≥80: EU/ROW
    		 189 3 192 384
        ≥80: USA
    		 13 8 10 31

    End points

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    End points reporting groups
    Reporting group title
    Dabigatran Etexilate 110mg
    Reporting group description
    		 Patients were orally administered Dabigatran Etexilate 110mg capsule twice daily (BID) for at least 6 months.

    Reporting group title
    Dabigatran Etexilate 150mg
    Reporting group description
    		 Patients were orally administered Dabigatran Etexilate 150mg capsule twice daily (BID) for at least 6 months.

    Reporting group title
    Warfarin
    Reporting group description
    		 Patients were orally administered warfarin 1 mg, 3 mg, or 5 mg tablets once daily for at least 6 months. The warfarin dose was titrated as needed to maintain the target International normalised ratio (INR) of 2.0 to 3.0 (2.0 to 2.6 for Japanese patients aged ≥70 years); 2.0 to 2.5 if feasible

    Subject analysis set title
    Warfarin (Excluding elder patient outside USA)
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Patients were orally administered warfarin once daily. The warfarin dose was titrated as needed to maintain the target INR of 2.0 to 3.0 ; 2.0 to 2.5 if feasible. Elderly patients who were outside the USA were excluded.

    Subject analysis set title
    All Dabigatran Etexilate
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Patients in combined Dabigatran Etexilate group (ie 110 mg DE + 150 mg DE).

    Primary: Time to first adjudicated ISTH MBE or CRNMBE.

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    End point title
    		 Time to first adjudicated ISTH MBE or CRNMBE.
    End point description
    The patients having event of time to first adjudicated International Society of Thrombosis and Haemostasis (ISTH) Major Bleeding Event (MBE) or Clinically Relevant Non Major Bleeding Event (CRNMBE).
    End point type
    Primary
    End point timeframe
    up to 30 months
    End point values
    		 Dabigatran Etexilate 110mg Dabigatran Etexilate 150mg Warfarin Warfarin (Excluding elder patient outside USA)
    Number of subjects analysed
    981 [1]
    763 [2]
    981 [3]
    764 [4]
    Units: participants with event
    151
    154
    264
    196
    Notes
    [1] - Full Analysis set (FAS) following the intention-to-treat principle.
    [2] - Full Analysis set (FAS) following the intention-to-treat principle.
    [3] - Full Analysis set (FAS) following the intention-to-treat principle.
    [4] - Full Analysis set (FAS) following the intention-to-treat principle.
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    A pre-defined hierarchical testing approach was used. This was the first step in hierarchy. The Cox proportional hazard model is stratified by age, non−elderly vs elderly [<70 or >=70 in Japan and <80 or >=80 years old elsewhere]. Hazard Ratio (HR) and Wald confidence intervals are derived from a Cox proportional-hazard model
    Comparison groups
    Dabigatran Etexilate 110mg v Warfarin
    Number of subjects included in analysis
    1962
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [5]
    P-value
    		 < 0.0001 [6]
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.52
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.42
         upper limit
    		 0.63
    Notes
    [5] - The upper bound of the Wald confidence interval (CI) of the HR of Dabigatran Etexilate 110mg vs Warfarin (one-sided 97.5%) was compared with this noninferiority margin for the testing of non-inferiority. All non-inferiority tests were based on a margin of 1.38.
    [6] - A pre-defined hierachical testing approach was used. P values for noninferiority were calculated at a one-sided alpha level of 0.025
    Statistical analysis title
    		 Statistical Analysis 2
    Statistical analysis description
    A pre-defined hierarchical testing approach was used. This was the second step in hierarchy. Unstratified Cox proportional hazards model was used and elderly patients outside the USA were excluded. Hazard Ratio (HR) and Wald confidence intervals are derived from a Cox proportional-hazard model. All non-inferiority tests were based on a margin of 1.38.
    Comparison groups
    Dabigatran Etexilate 150mg v Warfarin (Excluding elder patient outside USA)
    Number of subjects included in analysis
    1527
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    P-value
    		 < 0.001 [7]
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.72
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.58
         upper limit
    		 0.88
    Notes
    [7] - P-values for non-inferiority were calculated at a one-sided alpha level of 0.025
    Statistical analysis title
    		 Statistical Analysis 3
    Statistical analysis description
    A pre-defined hierarchical testing approach was used. This was the fourth step in hierarchy. The Cox proportional hazard model is stratified by age, non−elderly vs elderly [<70 or >=70 in Japan and <80 or >=80 years old elsewhere]. Hazard Ratio (HR) and Wald confidence intervals are derived from a Cox proportional-hazard model
    Comparison groups
    Dabigatran Etexilate 110mg v Warfarin
    Number of subjects included in analysis
    1962
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001 [8]
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.52
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.42
         upper limit
    		 0.63
    Notes
    [8] - Wald 2-sided p-value from (stratified) Cox proportional hazards model
    Statistical analysis title
    		 Statistical Analysis 4
    Statistical analysis description
    A pre-defined hierarchical testing approach was used. This was the sixth step in hierarchy. Unstratified Cox proportional hazards model was used and elderly patients outside the USA were excluded. Hazard Ratio (HR) and Wald confidence intervals are derived from a Cox proportional-hazard model
    Comparison groups
    Dabigatran Etexilate 150mg v Warfarin (Excluding elder patient outside USA)
    Number of subjects included in analysis
    1527
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.002 [9]
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.72
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.58
         upper limit
    		 0.88
    Notes
    [9] - Wald 2-sided p-value from (unstratified) Cox proportional hazards model

    Secondary: Time to adjudicated Undetermined cause of death

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    End point title
    		 Time to adjudicated Undetermined cause of death
    End point description
    The patients having event of time to adjudicated Undetermined cause of death. This is referred to a death not attributable to CV death or to a non-CV cause. Inability to classify the cause of death may have been due to lack of information (e.g. the only available information was “patient died”) or when there was insufficient supporting information or detail to assign the cause of death.
    End point type
    Secondary
    End point timeframe
    up to 30 months
    End point values
    		 Dabigatran Etexilate 110mg Dabigatran Etexilate 150mg Warfarin Warfarin (Excluding elder patient outside USA)
    Number of subjects analysed
    981 [10]
    763 [11]
    981 [12]
    764 [13]
    Units: participants with event
    4
    5
    4
    3
    Notes
    [10] - FAS
    [11] - FAS
    [12] - FAS
    [13] - FAS
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    The Cox proportional hazard model is stratified by age, non−elderly vs elderly [<70 or >=70 in Japan and <80 or >=80 years old elsewhere]. Hazard Ratio (HR) and Wald confidence intervals are derived from a Cox proportional-hazard model
    Comparison groups
    Dabigatran Etexilate 110mg v Warfarin
    Number of subjects included in analysis
    1962
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.9862 [14]
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.99
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.25
         upper limit
    		 3.95
    Notes
    [14] - Wald 2-sided p-value from (stratified) Cox proportional hazards model
    Statistical analysis title
    		 Statistical Analysis 2
    Statistical analysis description
    Unstratified Cox proportional hazards model was used and elderly patients outside the USA were excluded. Hazard Ratio (HR) and Wald confidence intervals are derived from a Cox proportional-hazard model
    Comparison groups
    Dabigatran Etexilate 150mg v Warfarin (Excluding elder patient outside USA)
    Number of subjects included in analysis
    1527
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.5277 [15]
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.59
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.38
         upper limit
    		 6.64
    Notes
    [15] - Wald 2-sided p-value from (unstratified) Cox proportional hazards model

    Secondary: Time to adjudicated Non-CV

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    End point title
    		 Time to adjudicated Non-CV
    End point description
    The patients having event of time to adjudicated Non-cardiovascular (Non-CV). Non-CV death was defined as any death with a specific cause that was not thought to be CV. These were possible examples of non-CV causes of death: Pulmonary, Renal, Gastrointestinal, Hepatobiliary, Pancreatic Infection(included sepsis), Inflammatory (e.g. systemic inflammatory response syndrome) or immune (including autoimmune), Haemorrhage that was neither CV bleeding nor a stroke, Non-CV procedure or surgery, Trauma, Suicide, Non-prescription drug reaction or overdose, Prescription drug reaction or overdose, Neurological (non-CV), Malignancy, Other non-CV
    End point type
    Secondary
    End point timeframe
    up to 30 months
    End point values
    		 Dabigatran Etexilate 110mg Dabigatran Etexilate 150mg Warfarin Warfarin (Excluding elder patient outside USA)
    Number of subjects analysed
    981 [16]
    763 [17]
    981 [18]
    764 [19]
    Units: participants with event
    14
    4
    13
    8
    Notes
    [16] - FAS
    [17] - FAS
    [18] - FAS
    [19] - FAS
    Statistical analysis title
    		 Statistical Analysis 2
    Statistical analysis description
    Unstratified Cox proportional hazards model was used and elderly patients outside the USA were excluded. Hazard Ratio (HR) and Wald confidence intervals are derived from a Cox proportional-hazard model
    Comparison groups
    Dabigatran Etexilate 150mg v Warfarin (Excluding elder patient outside USA)
    Number of subjects included in analysis
    1527
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.238 [20]
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.49
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.15
         upper limit
    		 1.61
    Notes
    [20] - Wald 2-sided p-value from (unstratified) Cox proportional hazards model
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    The Cox proportional hazard model is stratified by age, non−elderly vs elderly [<70 or >=70 in Japan and <80 or >=80 years old elsewhere]. Hazard Ratio (HR) and Wald confidence intervals are derived from a Cox proportional-hazard model
    Comparison groups
    Dabigatran Etexilate 110mg v Warfarin
    Number of subjects included in analysis
    1962
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.8853 [21]
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.06
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.5
         upper limit
    		 2.25
    Notes
    [21] - Wald 2-sided p-value from (stratified) Cox proportional hazards model

    Secondary: Time to adjudicated CV

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    End point title
    		 Time to adjudicated CV
    End point description
    The patients having event of time to adjudicated Cardiovascular (CV) death. CV death included death resulting from an acute myocardial infarction, sudden cardiac death, death due to heart failure, death due to stroke, death due to CV procedures, death due to CV haemorrhage, and death due to other CV causes.
    End point type
    Secondary
    End point timeframe
    up to 30 months
    End point values
    		 Dabigatran Etexilate 110mg Dabigatran Etexilate 150mg Warfarin Warfarin (Excluding elder patient outside USA)
    Number of subjects analysed
    981 [22]
    763 [23]
    981 [24]
    764 [25]
    Units: participants with event
    37
    21
    31
    24
    Notes
    [22] - FAS
    [23] - FAS
    [24] - FAS
    [25] - FAS
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    The Cox proportional hazard model is stratified by age, non−elderly vs elderly [<70 or >=70 in Japan and <80 or >=80 years old elsewhere]. Hazard Ratio (HR) and Wald confidence intervals are derived from a Cox proportional-hazard model
    Comparison groups
    Dabigatran Etexilate 110mg v Warfarin
    Number of subjects included in analysis
    1962
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.5252 [26]
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.17
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.72
         upper limit
    		 1.88
    Notes
    [26] - Wald 2-sided p-value from (stratified) Cox proportional hazards model
    Statistical analysis title
    		 Statistical Analysis 2
    Statistical analysis description
    Unstratified Cox proportional hazards model was used and elderly patients outside the USA were excluded. Hazard Ratio (HR) and Wald confidence intervals are derived from a Cox proportional-hazard model
    Comparison groups
    Dabigatran Etexilate 150mg v Warfarin (Excluding elder patient outside USA)
    Number of subjects included in analysis
    1527
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.567 [27]
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.84
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.47
         upper limit
    		 1.51
    Notes
    [27] - Wald 2-sided p-value from (unstratified) Cox proportional hazards model

    Secondary: Time to adjudicated all cause death

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    End point title
    		 Time to adjudicated all cause death
    End point description
    The patients having event of time to adjudicated all cause death. All cause death is defined as the death from any cause included CV death, non-CV death, and undetermined cause of death.
    End point type
    Secondary
    End point timeframe
    up to 30 months
    End point values
    		 Dabigatran Etexilate 110mg Dabigatran Etexilate 150mg Warfarin Warfarin (Excluding elder patient outside USA)
    Number of subjects analysed
    981 [28]
    763 [29]
    981 [30]
    764 [31]
    Units: participants with event
    55
    30
    48
    35
    Notes
    [28] - FAS
    [29] - FAS
    [30] - FAS
    [31] - FAS
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    The Cox proportional hazard model is stratified by age, non−elderly vs elderly [<70 or >=70 in Japan and <80 or >=80 years old elsewhere]. Hazard Ratio (HR) and Wald confidence intervals are derived from a Cox proportional-hazard model
    Comparison groups
    Dabigatran Etexilate 110mg v Warfarin
    Number of subjects included in analysis
    1962
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.5579 [32]
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.12
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.76
         upper limit
    		 1.65
    Notes
    [32] - Wald 2-sided p-value from (stratified) Cox proportional hazards model
    Statistical analysis title
    		 Statistical Analysis 2
    Statistical analysis description
    Unstratified Cox proportional hazards model was used and elderly patients outside the USA were excluded. Hazard Ratio (HR) and Wald confidence intervals are derived from a Cox proportional-hazard model.
    Comparison groups
    Dabigatran Etexilate 150mg v Warfarin (Excluding elder patient outside USA)
    Number of subjects included in analysis
    1527
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.4414 [33]
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.83
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.51
         upper limit
    		 1.34
    Notes
    [33] - Wald 2-sided p-value from (unstratified) Cox proportional hazards model

    Secondary: Time to first adjudicated MI

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    End point title
    		 Time to first adjudicated MI
    End point description
    The patients having event of time to first adjudicated Myocardial Infarction (MI).
    End point type
    Secondary
    End point timeframe
    up to 30 months
    End point values
    		 Dabigatran Etexilate 110mg Dabigatran Etexilate 150mg Warfarin Warfarin (Excluding elder patient outside USA)
    Number of subjects analysed
    981 [34]
    763 [35]
    981 [36]
    764 [37]
    Units: participants with event
    44
    26
    29
    22
    Notes
    [34] - FAS
    [35] - FAS
    [36] - FAS
    [37] - FAS
    Statistical analysis title
    		 Statistical Analysis 2
    Statistical analysis description
    Unstratified Cox proportional hazards model was used and elderly patients outside the USA were excluded. Hazard Ratio (HR) and Wald confidence intervals are derived from a Cox proportional-hazard model
    Comparison groups
    Dabigatran Etexilate 150mg v Warfarin (Excluding elder patient outside USA)
    Number of subjects included in analysis
    1527
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.6144 [38]
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.16
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.66
         upper limit
    		 2.04
    Notes
    [38] - Wald 2-sided p-value from (unstratified) Cox proportional hazards model
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    The Cox proportional hazard model is stratified by age, non−elderly vs elderly [<70 or >=70 in Japan and <80 or >=80 years old elsewhere]. Hazard Ratio (HR) and Wald confidence intervals are derived from a Cox proportional-hazard model
    Comparison groups
    Dabigatran Etexilate 110mg v Warfarin
    Number of subjects included in analysis
    1962
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.0861 [39]
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.51
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.94
         upper limit
    		 2.41
    Notes
    [39] - Wald 2-sided p-value from (stratified) Cox proportional hazards model

    Secondary: Time to first adjudicated Stroke

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    End point title
    		 Time to first adjudicated Stroke
    End point description
    The patients having event of time to first adjudicated Stroke. Stroke was defined as an acute episode of focal or global neurological dysfunction caused by brain, spinal cord, or retinal vascular injury as a result of haemorrhage or infarction
    End point type
    Secondary
    End point timeframe
    up to 30 months
    End point values
    		 Dabigatran Etexilate 110mg Dabigatran Etexilate 150mg Warfarin Warfarin (Excluding elder patient outside USA)
    Number of subjects analysed
    981
    763
    981
    764
    Units: participants with event
    17
    9
    13
    8
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    The Cox proportional hazard model is stratified by age, non−elderly vs elderly [<70 or >=70 in Japan and <80 or >=80 years old elsewhere].
    Comparison groups
    Dabigatran Etexilate 110mg v Warfarin
    Number of subjects included in analysis
    1962
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.4803 [40]
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.63
         upper limit
    		 2.67
    Notes
    [40] - Wald 2-sided p-value from (stratified) Cox proportional hazards model
    Statistical analysis title
    		 Statistical Analysis 2
    Statistical analysis description
    Unstratified Cox proportional hazards model was used and elderly patients outside the USA were excluded. Hazard Ratio (HR) and Wald confidence intervals are derived from a Cox proportional-hazard model
    Comparison groups
    Dabigatran Etexilate 150mg v Warfarin (Excluding elder patient outside USA)
    Number of subjects included in analysis
    1527
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.8537 [41]
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.09
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.42
         upper limit
    		 2.83
    Notes
    [41] - Wald 2-sided p-value from (unstratified) Cox proportional hazards model

    Secondary: Time to first adjudicated SE

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    End point title
    		 Time to first adjudicated SE
    End point description
    The patients having event of time to first adjudicated Systemic embolism (SE). SE is an acute vascular occlusion of the extremities or any organ (kidneys, mesenteric arteries, spleen, retina or grafts) and had to be documented by angiography, surgery, scintigraphy, or autopsy.
    End point type
    Secondary
    End point timeframe
    up to 30 months
    End point values
    		 Dabigatran Etexilate 110mg Dabigatran Etexilate 150mg Warfarin Warfarin (Excluding elder patient outside USA)
    Number of subjects analysed
    981 [42]
    763 [43]
    981 [44]
    764 [45]
    Units: participants with event
    3
    1
    3
    3
    Notes
    [42] - FAS
    [43] - FAS
    [44] - FAS
    [45] - FAS
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    The Cox proportional hazard model is stratified by age, non−elderly vs elderly [<70 or >=70 in Japan and <80 or >=80 years old lsewhere]. Hazard Ratio (HR) and Wald confidence intervals are derived from a Cox proportional-hazard model.
    Comparison groups
    Dabigatran Etexilate 110mg v Warfarin
    Number of subjects included in analysis
    1962
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.9388 [46]
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.94
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.19
         upper limit
    		 4.66
    Notes
    [46] - Wald 2-sided p-value from (stratified) Cox proportional hazards model
    Statistical analysis title
    		 Statistical Analysis 2
    Statistical analysis description
    Unstratified Cox proportional hazards model was used and elderly patients outside the USA were excluded. Hazard Ratio (HR) and Wald confidence intervals are derived from a Cox proportional-hazard model.
    Comparison groups
    Dabigatran Etexilate 150mg v Warfarin (Excluding elder patient outside USA)
    Number of subjects included in analysis
    1527
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.303 [47]
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.03
         upper limit
    		 2.93
    Notes
    [47] - Wald 2-sided p-value from (unstratified) Cox proportional hazards model

    Secondary: Time to first adjudicated ST

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    End point title
    		 Time to first adjudicated ST
    End point description
    The patients having event of time to first adjudicated Stent Thrombosis (ST).
    End point type
    Secondary
    End point timeframe
    up to 30 months
    End point values
    		 Dabigatran Etexilate 110mg Dabigatran Etexilate 150mg Warfarin Warfarin (Excluding elder patient outside USA)
    Number of subjects analysed
    981
    763
    981
    764
    Units: participants with event
    15
    7
    8
    7
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    The Cox proportional hazard model is stratified by age, non−elderly vs elderly [<70 or >=70 in Japan and <80 or >=80 years old elsewhere]. Hazard Ratio (HR) and Wald confidence intervals are derived from a Cox proportional-hazard model
    Comparison groups
    Dabigatran Etexilate 110mg v Warfarin
    Number of subjects included in analysis
    1962
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.1546 [48]
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.86
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.79
         upper limit
    		 4.4
    Notes
    [48] - Wald 2-sided p-value from (stratified) Cox proportional hazards model
    Statistical analysis title
    		 Statistical Analysis 2
    Statistical analysis description
    Unstratified Cox proportional hazards model was used and elderly patients outside the USA were excluded. Hazard Ratio (HR) and Wald confidence intervals are derived from a Cox proportional-hazard model
    Comparison groups
    Dabigatran Etexilate 150mg v Warfarin (Excluding elder patient outside USA)
    Number of subjects included in analysis
    1527
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.9789 [49]
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.99
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.35
         upper limit
    		 2.81
    Notes
    [49] - Wald 2-sided p-value from (unstratified) Cox proportional hazards model

    Secondary: Time to composite endpoint of death + MI + stroke

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    End point title
    		 Time to composite endpoint of death + MI + stroke
    End point description
    The patients having event of time to the composite endpoint of death + myocardial infarction (MI) + stroke
    End point type
    Secondary
    End point timeframe
    up to 30 months
    End point values
    		 Dabigatran Etexilate 110mg Dabigatran Etexilate 150mg Warfarin Warfarin (Excluding elder patient outside USA)
    Number of subjects analysed
    981 [50]
    763 [51]
    981 [52]
    764 [53]
    Units: participants with event
    107
    60
    80
    57
    Notes
    [50] - FAS
    [51] - FAS
    [52] - FAS
    [53] - FAS
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    The Cox proportional hazard model is stratified by age, non−elderly vs elderly [<70 or >=70 in Japan and <80 or >=80 years old elsewhere]. Hazard Ratio (HR) and Wald confidence intervals are derived from a Cox proportional-hazard model.
    Comparison groups
    Dabigatran Etexilate 110mg v Warfarin
    Number of subjects included in analysis
    1962
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.0484 [54]
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.34
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1
         upper limit
    		 1.79
    Notes
    [54] - Wald 2-sided p-value from (stratified) Cox proportional hazards model
    Statistical analysis title
    		 Statistical Analysis 2
    Statistical analysis description
    Unstratified Cox proportional hazards model was used and elderly patients outside the USA were excluded. Hazard Ratio (HR) and Wald confidence intervals are derived from a Cox proportional-hazard model
    Comparison groups
    Dabigatran Etexilate 150mg v Warfarin (Excluding elder patient outside USA)
    Number of subjects included in analysis
    1527
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.8903 [55]
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.03
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.71
         upper limit
    		 1.47
    Notes
    [55] - Wald 2-sided p-value from (unstratified) Cox proportional hazards model

    Secondary: Time to composite event of death or first thrombotic event

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    End point title
    		 Time to composite event of death or first thrombotic event
    End point description
    The patients having event of time to death or first thrombotic event (all death, myocardial infarction (MI), stroke/systemic embolism (SE))
    End point type
    Secondary
    End point timeframe
    up to 30 months
    End point values
    		 Dabigatran Etexilate 110mg Dabigatran Etexilate 150mg Warfarin Warfarin (Excluding elder patient outside USA) All Dabigatran Etexilate
    Number of subjects analysed
    981 [56]
    763 [57]
    981 [58]
    764 [59]
    1744 [60]
    Units: participants with event
    108
    60
    83
    60
    168
    Notes
    [56] - FAS
    [57] - FAS
    [58] - FAS
    [59] - FAS
    [60] - FAS
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    A pre-defined hierarchical testing approach was used. This was the fifth step in hierarchy. The Cox proportional hazard model is stratified by age, non−elderly vs elderly [<70 or >=70 in Japan and <80 or >=80 years old elsewhere].
    Comparison groups
    Warfarin v All Dabigatran Etexilate
    Number of subjects included in analysis
    2725
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [61]
    P-value
    		 = 0.1128 [62]
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.17
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.9
         upper limit
    		 1.53
    Notes
    [61] - The upper bound of the Wald confidence interval (CI) of the HR of All Dabigatran Etexilate (110mg and 150 mg) vs Warfarin (one-sided 97.5%) was compared with this noninferiority margin for the testing of non-inferiorityAll non-inferiority tests were based on a margin of 1.38.
    [62] - P values for noninferiority were calculated at a one-sided alpha level of 0.025
    Statistical analysis title
    		 Statistical Analysis 2
    Statistical analysis description
    The Cox proportional hazard model is stratified by age, non−elderly vs elderly [<70 or >=70 in Japan and <80 or >=80 years old elsewhere]. Hazard Ratio (HR) and Wald confidence intervals are derived from a Cox proportional-hazard model
    Comparison groups
    Dabigatran Etexilate 110mg v Warfarin
    Number of subjects included in analysis
    1962
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.072 [63]
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.98
         upper limit
    		 1.73
    Notes
    [63] - Wald 2-sided p-value from (stratified) Cox proportional hazards model
    Statistical analysis title
    		 Statistical Analysis 3
    Statistical analysis description
    Unstratified Cox proportional hazards model was used and elderly patients outside the USA were excluded. Hazard Ratio (HR) and Wald confidence intervals are derived from a Cox proportional-hazard model.
    Comparison groups
    Dabigatran Etexilate 150mg v Warfarin (Excluding elder patient outside USA)
    Number of subjects included in analysis
    1527
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.875 [64]
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.97
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.68
         upper limit
    		 1.39
    Notes
    [64] - Wald 2-sided p-value from (unstratified) Cox proportional hazards model

    Secondary: Time to first adjudicated unplanned revascularisation by PCI/CABG

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    End point title
    		 Time to first adjudicated unplanned revascularisation by PCI/CABG
    End point description
    The patients having event of time to first event for adjudicated unplanned revascularisation by Percutaneous Coronary Intervention/Coronary Artery Bypass Graft
    End point type
    Secondary
    End point timeframe
    up to 30 months
    End point values
    		 Dabigatran Etexilate 110mg Dabigatran Etexilate 150mg Warfarin Warfarin (Excluding elder patient outside USA)
    Number of subjects analysed
    981 [65]
    763 [66]
    981 [67]
    764 [68]
    Units: participants with event
    76
    51
    69
    52
    Notes
    [65] - FAS
    [66] - FAS
    [67] - FAS
    [68] - FAS
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    The Cox proportional hazard model is stratified by age, non−elderly vs elderly [<70 or >=70 in Japan and <80 or >=80 years old elsewhere]. Hazard Ratio (HR) and Wald confidence intervals are derived from a Cox proportional-hazard model
    Comparison groups
    Dabigatran Etexilate 110mg v Warfarin
    Number of subjects included in analysis
    1962
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.608 [69]
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.09
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.79
         upper limit
    		 1.51
    Notes
    [69] - Wald 2-sided p-value from (stratified) Cox proportional hazards model
    Statistical analysis title
    		 Statistical Analysis 2
    Statistical analysis description
    Unstratified Cox proportional hazards model was used and elderly patients outside the USA were excluded. Hazard Ratio (HR) and Wald confidence intervals are derived from a Cox proportional-hazard model.
    Comparison groups
    Dabigatran Etexilate 150mg v Warfarin (Excluding elder patient outside USA)
    Number of subjects included in analysis
    1527
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.8348 [70]
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.96
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.65
         upper limit
    		 1.41
    Notes
    [70] - Wald 2-sided p-value from (unstratified) Cox proportional hazards model

    Secondary: Time to death or first thrombotic event or unplanned revascularisation by PCI/CABG

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    End point title
    		 Time to death or first thrombotic event or unplanned revascularisation by PCI/CABG
    End point description
    The patients having event of time to death or first thrombotic event (all death, myocardial infarction, stroke/systemic embolism) or unplanned revascularisation by Percutaneous Coronary Intervention/Coronary Artery Bypass Graft
    End point type
    Secondary
    End point timeframe
    up to 30 months
    End point values
    		 Dabigatran Etexilate 110mg Dabigatran Etexilate 150mg Warfarin Warfarin (Excluding elder patient outside USA) All Dabigatran Etexilate
    Number of subjects analysed
    981 [71]
    763 [72]
    981 [73]
    764 [74]
    1744 [75]
    Units: participants with event
    149
    90
    131
    98
    239
    Notes
    [71] - FAS
    [72] - FAS
    [73] - FAS
    [74] - FAS
    [75] - FAS
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    A pre-defined hierarchical testing approach was used. This was the third step in hierarchy. The Cox proportional hazard model is stratified by age, non−elderly vs elderly [<70 or >=70 in Japan and <80 or >=80 years old elsewhere].
    Comparison groups
    Warfarin v All Dabigatran Etexilate
    Number of subjects included in analysis
    2725
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [76]
    P-value
    		 = 0.0047 [77]
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.04
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.84
         upper limit
    		 1.29
    Notes
    [76] - The upper bound of the Wald confidence interval (CI) of the HR of All Dabigatran Etexilate (110mg and 150 mg) vs Warfarin (one-sided 97.5%) was compared with this noninferiority margin for the testing of non-inferiorityAll non-inferiority tests were based on a margin of 1.38.
    [77] - P values for noninferiority were calculated at a one-sided alpha level of 0.025
    Statistical analysis title
    		 Statistical Analysis 3
    Statistical analysis description
    Unstratified Cox proportional hazards model was used and elderly patients outside the USA were excluded. Hazard Ratio (HR) and Wald confidence intervals are derived from a Cox proportional-hazard model.
    Comparison groups
    Dabigatran Etexilate 150mg v Warfarin (Excluding elder patient outside USA)
    Number of subjects included in analysis
    1527
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.4432 [78]
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.89
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.67
         upper limit
    		 1.19
    Notes
    [78] - Wald 2-sided p-value from (unstratified) Cox proportional hazards model
    Statistical analysis title
    		 Statistical Analysis 2
    Statistical analysis description
    The Cox proportional hazard model is stratified by age, non−elderly vs elderly [<70 or >=70 in Japan and <80 or >=80 years old elsewhere]. Hazard Ratio (HR) and Wald confidence intervals are derived from a Cox proportional-hazard model
    Comparison groups
    Dabigatran Etexilate 110mg v Warfarin
    Number of subjects included in analysis
    1962
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.3002 [79]
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.13
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.9
         upper limit
    		 1.43
    Notes
    [79] - Wald 2-sided p-value from (stratified) Cox proportional hazards model

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From the first drug administration until 6 days after the last drug administration.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    20.0
    Reporting groups
    Reporting group title
    Dabigatran Etexilate 110mg
    Reporting group description
    		 Patients were orally administered Dabigatran Etexilate 110mg capsule twice daily (BID) for atleast 6 months.

    Reporting group title
    Warfarin
    Reporting group description
    		 Patients were orally administered one tablet of warfarin 1 mg, 3 mg, or 5 mg once daily for atleast 6 months. The warfarin dose was titrated as needed to maintain the target International normalised ratio (INR) of 2.0 to 3.0 (2.0 to 2.6 for Japanese patients aged ≥70 years); 2.0 to 2.5 if feasible

    Reporting group title
    Dabigatran Etexilate 150mg
    Reporting group description
    		 Patients were orally administered Dabigatran Etexilate 150mg capsule twice daily (BID) for atleast 6 months.

    Serious adverse events
    		 Dabigatran Etexilate 110mg Warfarin Dabigatran Etexilate 150mg
    Total subjects affected by serious adverse events
         subjects affected / exposed
    415 / 972 (42.70%)
    396 / 948 (41.77%)
    300 / 758 (39.58%)
         number of deaths (all causes)
    38
    41
    24
         number of deaths resulting from adverse events
    38
    41
    24
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Acoustic neuroma
         subjects affected / exposed
    0 / 972 (0.00%)
    0 / 948 (0.00%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Adenocarcinoma gastric
         subjects affected / exposed
    0 / 972 (0.00%)
    0 / 948 (0.00%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Adenocarcinoma of colon
         subjects affected / exposed
    3 / 972 (0.31%)
    0 / 948 (0.00%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    B-cell lymphoma
         subjects affected / exposed
    1 / 972 (0.10%)
    1 / 948 (0.11%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Basal cell carcinoma
         subjects affected / exposed
    5 / 972 (0.51%)
    4 / 948 (0.42%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Benign gastrointestinal neoplasm
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bladder cancer
         subjects affected / exposed
    2 / 972 (0.21%)
    0 / 948 (0.00%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bladder cancer recurrent
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bladder neoplasm
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bladder transitional cell carcinoma
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bone neoplasm
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Breast cancer
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Bronchial carcinoma
         subjects affected / exposed
    0 / 972 (0.00%)
    0 / 948 (0.00%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Carcinoma in situ of penis
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cerebral haemangioma
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Chronic lymphocytic leukaemia
         subjects affected / exposed
    0 / 972 (0.00%)
    2 / 948 (0.21%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Colon cancer
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Colon neoplasm
         subjects affected / exposed
    0 / 972 (0.00%)
    0 / 948 (0.00%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Colorectal adenocarcinoma
         subjects affected / exposed
    0 / 972 (0.00%)
    0 / 948 (0.00%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Colorectal cancer
         subjects affected / exposed
    0 / 972 (0.00%)
    2 / 948 (0.21%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastric cancer
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatocellular carcinoma
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lung adenocarcinoma
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Lung adenocarcinoma stage IV
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lung cancer metastatic
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Lung carcinoma cell type unspecified stage I
         subjects affected / exposed
    0 / 972 (0.00%)
    0 / 948 (0.00%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lymphocytic leukaemia
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lung neoplasm malignant
         subjects affected / exposed
    3 / 972 (0.31%)
    0 / 948 (0.00%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Lymphoma
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Malignant melanoma
         subjects affected / exposed
    1 / 972 (0.10%)
    1 / 948 (0.11%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Mantle cell lymphoma
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Meningioma
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Metastases to bone
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Metastases to liver
         subjects affected / exposed
    2 / 972 (0.21%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Metastases to lung
         subjects affected / exposed
    0 / 972 (0.00%)
    0 / 948 (0.00%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Metastases to spine
         subjects affected / exposed
    1 / 972 (0.10%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    Myelodysplastic syndrome
         subjects affected / exposed
    0 / 972 (0.00%)
    0 / 948 (0.00%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Myelofibrosis
         subjects affected / exposed
    0 / 972 (0.00%)
    0 / 948 (0.00%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Non-small cell lung cancer
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Non-Hodgkin's lymphoma
         subjects affected / exposed
    0 / 972 (0.00%)
    2 / 948 (0.21%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Non-small cell lung cancer recurrent
         subjects affected / exposed
    0 / 972 (0.00%)
    0 / 948 (0.00%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pancreatic carcinoma
         subjects affected / exposed
    0 / 972 (0.00%)
    2 / 948 (0.21%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    Plasma cell myeloma
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Prostate cancer
         subjects affected / exposed
    6 / 972 (0.62%)
    3 / 948 (0.32%)
    2 / 758 (0.26%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Rectal adenocarcinoma
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Rectal cancer
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Rectal cancer stage 0
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal cancer
         subjects affected / exposed
    0 / 972 (0.00%)
    0 / 948 (0.00%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal cell carcinoma
         subjects affected / exposed
    1 / 972 (0.10%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal neoplasm
         subjects affected / exposed
    0 / 972 (0.00%)
    0 / 948 (0.00%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Skin cancer
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Small cell lung cancer
         subjects affected / exposed
    0 / 972 (0.00%)
    0 / 948 (0.00%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Squamous cell carcinoma
         subjects affected / exposed
    1 / 972 (0.10%)
    1 / 948 (0.11%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Squamous cell carcinoma of skin
         subjects affected / exposed
    1 / 972 (0.10%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Squamous cell carcinoma of the tongue
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Testicular neoplasm
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Transitional cell carcinoma
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Transitional cell carcinoma recurrent
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Tumour ulceration
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Urinary bladder adenoma
         subjects affected / exposed
    0 / 972 (0.00%)
    0 / 948 (0.00%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Aneurysm
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Angiodysplasia
         subjects affected / exposed
    1 / 972 (0.10%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Aortic aneurysm
         subjects affected / exposed
    1 / 972 (0.10%)
    1 / 948 (0.11%)
    2 / 758 (0.26%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Aortic dissection
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Aortic dissection rupture
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    Aortic necrosis
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Aortic stenosis
         subjects affected / exposed
    3 / 972 (0.31%)
    2 / 948 (0.21%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Aortic thrombosis
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Aortitis
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Arterial occlusive disease
         subjects affected / exposed
    0 / 972 (0.00%)
    0 / 948 (0.00%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Arteriovenous fistula
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Circulatory collapse
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diabetic vascular disorder
         subjects affected / exposed
    0 / 972 (0.00%)
    0 / 948 (0.00%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Extremity necrosis
         subjects affected / exposed
    1 / 972 (0.10%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Femoral artery dissection
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haematoma
         subjects affected / exposed
    2 / 972 (0.21%)
    7 / 948 (0.74%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    1 / 2
    6 / 7
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haemorrhage
         subjects affected / exposed
    2 / 972 (0.21%)
    6 / 948 (0.63%)
    2 / 758 (0.26%)
         occurrences causally related to treatment / all
    2 / 2
    4 / 6
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypertension
         subjects affected / exposed
    6 / 972 (0.62%)
    1 / 948 (0.11%)
    5 / 758 (0.66%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 1
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypertensive crisis
         subjects affected / exposed
    8 / 972 (0.82%)
    11 / 948 (1.16%)
    3 / 758 (0.40%)
         occurrences causally related to treatment / all
    0 / 9
    0 / 13
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypertensive emergency
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypotension
         subjects affected / exposed
    1 / 972 (0.10%)
    6 / 948 (0.63%)
    2 / 758 (0.26%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 6
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypovolaemic shock
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Iliac artery occlusion
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Intermittent claudication
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ischaemia
         subjects affected / exposed
    1 / 972 (0.10%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Orthostatic hypotension
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Peripheral arterial occlusive disease
         subjects affected / exposed
    5 / 972 (0.51%)
    5 / 948 (0.53%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 5
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Peripheral artery occlusion
         subjects affected / exposed
    0 / 972 (0.00%)
    2 / 948 (0.21%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Peripheral artery stenosis
         subjects affected / exposed
    1 / 972 (0.10%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Peripheral embolism
         subjects affected / exposed
    2 / 972 (0.21%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Peripheral ischaemia
         subjects affected / exposed
    0 / 972 (0.00%)
    0 / 948 (0.00%)
    2 / 758 (0.26%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Shock
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Temporal arteritis
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Thrombophlebitis superficial
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Thrombosis
         subjects affected / exposed
    2 / 972 (0.21%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Adverse drug reaction
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Asthenia
         subjects affected / exposed
    0 / 972 (0.00%)
    5 / 948 (0.53%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 5
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac death
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Chest discomfort
         subjects affected / exposed
    3 / 972 (0.31%)
    0 / 948 (0.00%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Chest pain
         subjects affected / exposed
    14 / 972 (1.44%)
    15 / 948 (1.58%)
    15 / 758 (1.98%)
         occurrences causally related to treatment / all
    0 / 14
    0 / 15
    0 / 17
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Death
         subjects affected / exposed
    8 / 972 (0.82%)
    5 / 948 (0.53%)
    6 / 758 (0.79%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 5
    0 / 6
         deaths causally related to treatment / all
    0 / 8
    0 / 5
    0 / 6
    Device related thrombosis
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Drug effect increased
         subjects affected / exposed
    0 / 972 (0.00%)
    0 / 948 (0.00%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gait disturbance
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    General physical health deterioration
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Impaired healing
         subjects affected / exposed
    2 / 972 (0.21%)
    1 / 948 (0.11%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Implant site haematoma
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Injection site haematoma
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Localised oedema
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Malaise
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Medical device site haematoma
         subjects affected / exposed
    0 / 972 (0.00%)
    0 / 948 (0.00%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Multiple organ dysfunction syndrome
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Non-cardiac chest pain
         subjects affected / exposed
    3 / 972 (0.31%)
    1 / 948 (0.11%)
    3 / 758 (0.40%)
         occurrences causally related to treatment / all
    1 / 3
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Oedema
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Oedema peripheral
         subjects affected / exposed
    0 / 972 (0.00%)
    0 / 948 (0.00%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Puncture site haemorrhage
         subjects affected / exposed
    0 / 972 (0.00%)
    2 / 948 (0.21%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    1 / 972 (0.10%)
    1 / 948 (0.11%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Sudden cardiac death
         subjects affected / exposed
    4 / 972 (0.41%)
    1 / 948 (0.11%)
    2 / 758 (0.26%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 4
    0 / 1
    0 / 2
    Sudden death
         subjects affected / exposed
    2 / 972 (0.21%)
    7 / 948 (0.74%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 7
    0 / 1
         deaths causally related to treatment / all
    0 / 2
    0 / 7
    0 / 1
    Ulcer
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ulcer haemorrhage
         subjects affected / exposed
    0 / 972 (0.00%)
    0 / 948 (0.00%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vascular stent occlusion
         subjects affected / exposed
    0 / 972 (0.00%)
    0 / 948 (0.00%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vascular stent restenosis
         subjects affected / exposed
    5 / 972 (0.51%)
    3 / 948 (0.32%)
    4 / 758 (0.53%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 3
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vascular stent stenosis
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vascular stent thrombosis
         subjects affected / exposed
    25 / 972 (2.57%)
    17 / 948 (1.79%)
    10 / 758 (1.32%)
         occurrences causally related to treatment / all
    4 / 25
    2 / 17
    2 / 10
         deaths causally related to treatment / all
    0 / 4
    0 / 3
    1 / 2
    Immune system disorders
    Drug hypersensitivity
         subjects affected / exposed
    0 / 972 (0.00%)
    0 / 948 (0.00%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Benign prostatic hyperplasia
         subjects affected / exposed
    2 / 972 (0.21%)
    0 / 948 (0.00%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Prostatitis
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vaginal haemorrhage
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Acute pulmonary oedema
         subjects affected / exposed
    4 / 972 (0.41%)
    2 / 948 (0.21%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Acute respiratory failure
         subjects affected / exposed
    1 / 972 (0.10%)
    3 / 948 (0.32%)
    3 / 758 (0.40%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Asthma
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bronchiectasis
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bronchospasm
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    5 / 972 (0.51%)
    6 / 948 (0.63%)
    6 / 758 (0.79%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 8
    0 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Chronic respiratory failure
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cough
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dyspnoea
         subjects affected / exposed
    11 / 972 (1.13%)
    17 / 948 (1.79%)
    10 / 758 (1.32%)
         occurrences causally related to treatment / all
    0 / 16
    0 / 18
    0 / 11
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    Dyspnoea at rest
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dyspnoea exertional
         subjects affected / exposed
    2 / 972 (0.21%)
    0 / 948 (0.00%)
    2 / 758 (0.26%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Epistaxis
         subjects affected / exposed
    3 / 972 (0.31%)
    9 / 948 (0.95%)
    3 / 758 (0.40%)
         occurrences causally related to treatment / all
    2 / 3
    9 / 11
    3 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haemoptysis
         subjects affected / exposed
    4 / 972 (0.41%)
    5 / 948 (0.53%)
    2 / 758 (0.26%)
         occurrences causally related to treatment / all
    3 / 4
    5 / 5
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haemothorax
         subjects affected / exposed
    0 / 972 (0.00%)
    0 / 948 (0.00%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypoxia
         subjects affected / exposed
    0 / 972 (0.00%)
    0 / 948 (0.00%)
    2 / 758 (0.26%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Interstitial lung disease
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Laryngeal oedema
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lung disorder
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pleural effusion
         subjects affected / exposed
    8 / 972 (0.82%)
    3 / 948 (0.32%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 10
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pleurisy
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonia aspiration
         subjects affected / exposed
    1 / 972 (0.10%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    Pneumothorax
         subjects affected / exposed
    3 / 972 (0.31%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    1 / 972 (0.10%)
    2 / 948 (0.21%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pulmonary fibrosis
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    2 / 758 (0.26%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pulmonary hypertension
         subjects affected / exposed
    1 / 972 (0.10%)
    2 / 948 (0.21%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pulmonary mass
         subjects affected / exposed
    0 / 972 (0.00%)
    0 / 948 (0.00%)
    2 / 758 (0.26%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pulmonary oedema
         subjects affected / exposed
    7 / 972 (0.72%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory failure
         subjects affected / exposed
    1 / 972 (0.10%)
    1 / 948 (0.11%)
    4 / 758 (0.53%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Sleep apnoea syndrome
         subjects affected / exposed
    0 / 972 (0.00%)
    2 / 948 (0.21%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Alcohol abuse
         subjects affected / exposed
    0 / 972 (0.00%)
    0 / 948 (0.00%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Anxiety
         subjects affected / exposed
    1 / 972 (0.10%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Anxiety disorder
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Confusional state
         subjects affected / exposed
    0 / 972 (0.00%)
    2 / 948 (0.21%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Delirium
         subjects affected / exposed
    3 / 972 (0.31%)
    0 / 948 (0.00%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hallucination, visual
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Mental status changes
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Paranoia
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Transient psychosis
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Product issues
    Device malfunction
         subjects affected / exposed
    0 / 972 (0.00%)
    0 / 948 (0.00%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Anticoagulation drug level above therapeutic
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood creatinine increased
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood pressure abnormal
         subjects affected / exposed
    0 / 972 (0.00%)
    0 / 948 (0.00%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood pressure increased
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood urine
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood urine present
         subjects affected / exposed
    0 / 972 (0.00%)
    0 / 948 (0.00%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    C-reactive protein increased
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haematocrit decreased
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haemoglobin decreased
         subjects affected / exposed
    0 / 972 (0.00%)
    2 / 948 (0.21%)
    4 / 758 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
    2 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatic enzyme increased
         subjects affected / exposed
    0 / 972 (0.00%)
    0 / 948 (0.00%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    International normalised ratio increased
         subjects affected / exposed
    0 / 972 (0.00%)
    9 / 948 (0.95%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    8 / 9
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Liver function test increased
         subjects affected / exposed
    0 / 972 (0.00%)
    0 / 948 (0.00%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Occult blood positive
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Troponin increased
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Ankle fracture
         subjects affected / exposed
    2 / 972 (0.21%)
    0 / 948 (0.00%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Arterial bypass occlusion
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Brain contusion
         subjects affected / exposed
    1 / 972 (0.10%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Chemical burn
         subjects affected / exposed
    0 / 972 (0.00%)
    0 / 948 (0.00%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Clavicle fracture
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Concussion
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Confusion postoperative
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Contusion
         subjects affected / exposed
    1 / 972 (0.10%)
    1 / 948 (0.11%)
    2 / 758 (0.26%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Coronary artery restenosis
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Fall
         subjects affected / exposed
    4 / 972 (0.41%)
    5 / 948 (0.53%)
    2 / 758 (0.26%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 6
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Femoral neck fracture
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Femur fracture
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    2 / 758 (0.26%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hand fracture
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Head injury
         subjects affected / exposed
    1 / 972 (0.10%)
    2 / 948 (0.21%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hip fracture
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Iatrogenic injury
         subjects affected / exposed
    0 / 972 (0.00%)
    0 / 948 (0.00%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Incisional hernia
         subjects affected / exposed
    1 / 972 (0.10%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infusion related reaction
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Joint injury
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Laceration
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ligament injury
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Limb injury
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lumbar vertebral fracture
         subjects affected / exposed
    0 / 972 (0.00%)
    2 / 948 (0.21%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Meniscus injury
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Multiple fractures
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Near drowning
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Overdose
         subjects affected / exposed
    0 / 972 (0.00%)
    3 / 948 (0.32%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    3 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pelvic fracture
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Periprosthetic fracture
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Post procedural complication
         subjects affected / exposed
    2 / 972 (0.21%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Post procedural haemorrhage
         subjects affected / exposed
    1 / 972 (0.10%)
    2 / 948 (0.21%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Post procedural myocardial infarction
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Postoperative fever
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Postoperative renal failure
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Postoperative thrombosis
         subjects affected / exposed
    0 / 972 (0.00%)
    0 / 948 (0.00%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Procedural complication
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pubis fracture
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Rib fracture
         subjects affected / exposed
    1 / 972 (0.10%)
    3 / 948 (0.32%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Road traffic accident
         subjects affected / exposed
    0 / 972 (0.00%)
    2 / 948 (0.21%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Skull fracture
         subjects affected / exposed
    0 / 972 (0.00%)
    0 / 948 (0.00%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Skull fractured base
         subjects affected / exposed
    1 / 972 (0.10%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Spinal compression fracture
         subjects affected / exposed
    0 / 972 (0.00%)
    2 / 948 (0.21%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Splenic injury
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Sternal fracture
         subjects affected / exposed
    0 / 972 (0.00%)
    0 / 948 (0.00%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Subarachnoid haemorrhage
         subjects affected / exposed
    1 / 972 (0.10%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Subdural haematoma
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Subdural haemorrhage
         subjects affected / exposed
    1 / 972 (0.10%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Toxicity to various agents
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Traumatic intracranial haemorrhage
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Upper limb fracture
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vascular graft occlusion
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vascular pseudoaneurysm
         subjects affected / exposed
    1 / 972 (0.10%)
    3 / 948 (0.32%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Wound
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Wound dehiscence
         subjects affected / exposed
    0 / 972 (0.00%)
    0 / 948 (0.00%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Wrist fracture
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Congenital, familial and genetic disorders
    Generalised resistance to thyroid hormone
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Phimosis
         subjects affected / exposed
    0 / 972 (0.00%)
    0 / 948 (0.00%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Venous angioma of brain
         subjects affected / exposed
    0 / 972 (0.00%)
    0 / 948 (0.00%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Acute coronary syndrome
         subjects affected / exposed
    1 / 972 (0.10%)
    4 / 948 (0.42%)
    2 / 758 (0.26%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 4
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Acute left ventricular failure
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Acute myocardial infarction
         subjects affected / exposed
    20 / 972 (2.06%)
    15 / 948 (1.58%)
    14 / 758 (1.85%)
         occurrences causally related to treatment / all
    1 / 21
    0 / 16
    2 / 14
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Acute right ventricular failure
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Angina pectoris
         subjects affected / exposed
    20 / 972 (2.06%)
    18 / 948 (1.90%)
    18 / 758 (2.37%)
         occurrences causally related to treatment / all
    1 / 22
    0 / 20
    1 / 21
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Angina unstable
         subjects affected / exposed
    26 / 972 (2.67%)
    13 / 948 (1.37%)
    15 / 758 (1.98%)
         occurrences causally related to treatment / all
    2 / 31
    0 / 17
    0 / 16
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Aortic valve disease
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Aortic valve disease mixed
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Aortic valve incompetence
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Aortic valve stenosis
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Arrhythmia
         subjects affected / exposed
    2 / 972 (0.21%)
    0 / 948 (0.00%)
    2 / 758 (0.26%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 4
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Arrhythmia supraventricular
         subjects affected / exposed
    1 / 972 (0.10%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Arteriosclerosis coronary artery
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    44 / 972 (4.53%)
    34 / 948 (3.59%)
    36 / 758 (4.75%)
         occurrences causally related to treatment / all
    0 / 51
    0 / 41
    0 / 44
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Atrial flutter
         subjects affected / exposed
    18 / 972 (1.85%)
    6 / 948 (0.63%)
    8 / 758 (1.06%)
         occurrences causally related to treatment / all
    0 / 20
    0 / 8
    0 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Atrial tachycardia
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Atrial thrombosis
         subjects affected / exposed
    2 / 972 (0.21%)
    1 / 948 (0.11%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Atrioventricular block second degree
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bradyarrhythmia
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bradycardia
         subjects affected / exposed
    5 / 972 (0.51%)
    6 / 948 (0.63%)
    5 / 758 (0.66%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 6
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac arrest
         subjects affected / exposed
    4 / 972 (0.41%)
    5 / 948 (0.53%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 4
    1 / 5
    0 / 1
         deaths causally related to treatment / all
    0 / 2
    1 / 4
    0 / 1
    Cardiac asthma
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac failure
         subjects affected / exposed
    48 / 972 (4.94%)
    46 / 948 (4.85%)
    30 / 758 (3.96%)
         occurrences causally related to treatment / all
    0 / 56
    0 / 57
    0 / 41
         deaths causally related to treatment / all
    0 / 2
    0 / 1
    0 / 2
    Cardiac failure acute
         subjects affected / exposed
    7 / 972 (0.72%)
    4 / 948 (0.42%)
    5 / 758 (0.66%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 4
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    Cardiac failure chronic
         subjects affected / exposed
    7 / 972 (0.72%)
    3 / 948 (0.32%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac failure congestive
         subjects affected / exposed
    14 / 972 (1.44%)
    19 / 948 (2.00%)
    13 / 758 (1.72%)
         occurrences causally related to treatment / all
    0 / 18
    0 / 30
    0 / 26
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    0 / 1
    Cardiac flutter
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac tamponade
         subjects affected / exposed
    1 / 972 (0.10%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac ventricular thrombosis
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiogenic shock
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Coronary artery disease
         subjects affected / exposed
    6 / 972 (0.62%)
    7 / 948 (0.74%)
    6 / 758 (0.79%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 7
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Coronary artery insufficiency
         subjects affected / exposed
    0 / 972 (0.00%)
    2 / 948 (0.21%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Coronary artery occlusion
         subjects affected / exposed
    0 / 972 (0.00%)
    0 / 948 (0.00%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Coronary artery stenosis
         subjects affected / exposed
    4 / 972 (0.41%)
    3 / 948 (0.32%)
    12 / 758 (1.58%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 4
    0 / 14
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Heart valve incompetence
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Intracardiac thrombus
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ischaemic cardiomyopathy
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    2 / 758 (0.26%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Left ventricular failure
         subjects affected / exposed
    3 / 972 (0.31%)
    0 / 948 (0.00%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Microvascular coronary artery disease
         subjects affected / exposed
    0 / 972 (0.00%)
    0 / 948 (0.00%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Mitral valve prolapse
         subjects affected / exposed
    0 / 972 (0.00%)
    0 / 948 (0.00%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Mitral valve incompetence
         subjects affected / exposed
    5 / 972 (0.51%)
    3 / 948 (0.32%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Myocardial fibrosis
         subjects affected / exposed
    0 / 972 (0.00%)
    0 / 948 (0.00%)
    2 / 758 (0.26%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Myocardial ischaemia
         subjects affected / exposed
    3 / 972 (0.31%)
    5 / 948 (0.53%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 3
    1 / 5
    0 / 1
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    17 / 972 (1.75%)
    8 / 948 (0.84%)
    8 / 758 (1.06%)
         occurrences causally related to treatment / all
    2 / 17
    1 / 8
    1 / 8
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
    Palpitations
         subjects affected / exposed
    1 / 972 (0.10%)
    2 / 948 (0.21%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pericardial effusion
         subjects affected / exposed
    2 / 972 (0.21%)
    0 / 948 (0.00%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pericarditis constrictive
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pericarditis
         subjects affected / exposed
    0 / 972 (0.00%)
    0 / 948 (0.00%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Right ventricular failure
         subjects affected / exposed
    0 / 972 (0.00%)
    3 / 948 (0.32%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Silent myocardial infarction
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Sinus arrest
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Sinus bradycardia
         subjects affected / exposed
    1 / 972 (0.10%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Sinus node dysfunction
         subjects affected / exposed
    5 / 972 (0.51%)
    3 / 948 (0.32%)
    2 / 758 (0.26%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Supraventricular tachycardia
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Systolic dysfunction
         subjects affected / exposed
    0 / 972 (0.00%)
    0 / 948 (0.00%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Tachyarrhythmia
         subjects affected / exposed
    2 / 972 (0.21%)
    0 / 948 (0.00%)
    2 / 758 (0.26%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Tachycardia
         subjects affected / exposed
    2 / 972 (0.21%)
    1 / 948 (0.11%)
    5 / 758 (0.66%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Tricuspid valve incompetence
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Trifascicular block
         subjects affected / exposed
    0 / 972 (0.00%)
    0 / 948 (0.00%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ventricle rupture
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Ventricular extrasystoles
         subjects affected / exposed
    0 / 972 (0.00%)
    0 / 948 (0.00%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ventricular arrhythmia
         subjects affected / exposed
    0 / 972 (0.00%)
    0 / 948 (0.00%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ventricular fibrillation
         subjects affected / exposed
    3 / 972 (0.31%)
    0 / 948 (0.00%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Ventricular tachycardia
         subjects affected / exposed
    7 / 972 (0.72%)
    3 / 948 (0.32%)
    5 / 758 (0.66%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 5
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Altered state of consciousness
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Basal ganglia haemorrhage
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Basal ganglia stroke
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Brain injury
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Brain oedema
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Brain stem infarction
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Carotid arteriosclerosis
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Carotid artery occlusion
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Carotid artery stenosis
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Carotid sinus syndrome
         subjects affected / exposed
    0 / 972 (0.00%)
    0 / 948 (0.00%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cerebellar haemorrhage
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cerebral haemorrhage
         subjects affected / exposed
    0 / 972 (0.00%)
    2 / 948 (0.21%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    2 / 2
    0 / 0
    Cerebral infarction
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cerebral ischaemia
         subjects affected / exposed
    0 / 972 (0.00%)
    0 / 948 (0.00%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cerebrovascular accident
         subjects affected / exposed
    3 / 972 (0.31%)
    4 / 948 (0.42%)
    4 / 758 (0.53%)
         occurrences causally related to treatment / all
    0 / 3
    1 / 4
    3 / 4
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    1 / 1
    Dementia
         subjects affected / exposed
    3 / 972 (0.31%)
    0 / 948 (0.00%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diplegia
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Disturbance in attention
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dizziness
         subjects affected / exposed
    2 / 972 (0.21%)
    3 / 948 (0.32%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dizziness postural
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Drop attacks
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Encephalomalacia
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Encephalopathy
         subjects affected / exposed
    0 / 972 (0.00%)
    0 / 948 (0.00%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Epilepsy
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Facial paresis
         subjects affected / exposed
    0 / 972 (0.00%)
    0 / 948 (0.00%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haemorrhage intracranial
         subjects affected / exposed
    1 / 972 (0.10%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haemorrhagic stroke
         subjects affected / exposed
    0 / 972 (0.00%)
    0 / 948 (0.00%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    Headache
         subjects affected / exposed
    0 / 972 (0.00%)
    0 / 948 (0.00%)
    3 / 758 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hemiplegia
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ischaemic stroke
         subjects affected / exposed
    4 / 972 (0.41%)
    1 / 948 (0.11%)
    4 / 758 (0.53%)
         occurrences causally related to treatment / all
    1 / 4
    0 / 1
    1 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lacunar infarction
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lateral medullary syndrome
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Loss of consciousness
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Mental impairment
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Metabolic encephalopathy
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Migraine
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Movement disorder
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Post herpetic neuralgia
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Quadriparesis
         subjects affected / exposed
    0 / 972 (0.00%)
    0 / 948 (0.00%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Sciatica
         subjects affected / exposed
    1 / 972 (0.10%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Seizure
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Somnolence
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Spinal claudication
         subjects affected / exposed
    0 / 972 (0.00%)
    0 / 948 (0.00%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Syncope
         subjects affected / exposed
    9 / 972 (0.93%)
    7 / 948 (0.74%)
    10 / 758 (1.32%)
         occurrences causally related to treatment / all
    1 / 9
    0 / 7
    0 / 16
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Tension headache
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Transient ischaemic attack
         subjects affected / exposed
    4 / 972 (0.41%)
    1 / 948 (0.11%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    1 / 4
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    6 / 972 (0.62%)
    7 / 948 (0.74%)
    7 / 758 (0.92%)
         occurrences causally related to treatment / all
    4 / 6
    3 / 7
    4 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Anaemia macrocytic
         subjects affected / exposed
    0 / 972 (0.00%)
    0 / 948 (0.00%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haemorrhagic anaemia
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Iron deficiency anaemia
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lymphadenopathy
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Normochromic normocytic anaemia
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Thrombocytopenia
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    Deafness
         subjects affected / exposed
    1 / 972 (0.10%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vertigo
         subjects affected / exposed
    3 / 972 (0.31%)
    0 / 948 (0.00%)
    3 / 758 (0.40%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vestibular disorder
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Eye disorders
    Blindness transient
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cataract
         subjects affected / exposed
    2 / 972 (0.21%)
    3 / 948 (0.32%)
    3 / 758 (0.40%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Eye haemorrhage
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Glaucoma
         subjects affected / exposed
    3 / 972 (0.31%)
    2 / 948 (0.21%)
    2 / 758 (0.26%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Neovascular age-related macular degeneration
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Retinal detachment
         subjects affected / exposed
    1 / 972 (0.10%)
    3 / 948 (0.32%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vitreous haemorrhage
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal hernia
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Abdominal pain
         subjects affected / exposed
    0 / 972 (0.00%)
    2 / 948 (0.21%)
    3 / 758 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Abdominal pain upper
         subjects affected / exposed
    1 / 972 (0.10%)
    2 / 948 (0.21%)
    2 / 758 (0.26%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Chronic gastritis
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Colitis
         subjects affected / exposed
    2 / 972 (0.21%)
    0 / 948 (0.00%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Colitis ischaemic
         subjects affected / exposed
    0 / 972 (0.00%)
    0 / 948 (0.00%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dental cyst
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diverticulum
         subjects affected / exposed
    0 / 972 (0.00%)
    2 / 948 (0.21%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dyspepsia
         subjects affected / exposed
    0 / 972 (0.00%)
    0 / 948 (0.00%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dysphagia
         subjects affected / exposed
    2 / 972 (0.21%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Faecaloma
         subjects affected / exposed
    0 / 972 (0.00%)
    0 / 948 (0.00%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastric haemorrhage
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastric polyps
         subjects affected / exposed
    0 / 972 (0.00%)
    0 / 948 (0.00%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastritis
         subjects affected / exposed
    1 / 972 (0.10%)
    2 / 948 (0.21%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastritis erosive
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastritis haemorrhagic
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal haemorrhage
         subjects affected / exposed
    9 / 972 (0.93%)
    13 / 948 (1.37%)
    5 / 758 (0.66%)
         occurrences causally related to treatment / all
    9 / 9
    13 / 14
    7 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal polyp haemorrhage
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal tract irritation
         subjects affected / exposed
    0 / 972 (0.00%)
    0 / 948 (0.00%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrooesophageal reflux disease
         subjects affected / exposed
    1 / 972 (0.10%)
    1 / 948 (0.11%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gingival bleeding
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haematemesis
         subjects affected / exposed
    1 / 972 (0.10%)
    2 / 948 (0.21%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haematochezia
         subjects affected / exposed
    2 / 972 (0.21%)
    2 / 948 (0.21%)
    3 / 758 (0.40%)
         occurrences causally related to treatment / all
    1 / 2
    2 / 2
    1 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hiatus hernia
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ileus
         subjects affected / exposed
    0 / 972 (0.00%)
    0 / 948 (0.00%)
    2 / 758 (0.26%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Incarcerated inguinal hernia
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Inguinal hernia
         subjects affected / exposed
    1 / 972 (0.10%)
    3 / 948 (0.32%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Intestinal haemorrhage
         subjects affected / exposed
    1 / 972 (0.10%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Intestinal obstruction
         subjects affected / exposed
    1 / 972 (0.10%)
    2 / 948 (0.21%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Large intestine polyp
         subjects affected / exposed
    1 / 972 (0.10%)
    2 / 948 (0.21%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lower gastrointestinal haemorrhage
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Melaena
         subjects affected / exposed
    4 / 972 (0.41%)
    4 / 948 (0.42%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    3 / 4
    3 / 4
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Oesophagitis
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pancreatitis
         subjects affected / exposed
    1 / 972 (0.10%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pancreatitis acute
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Rectal haemorrhage
         subjects affected / exposed
    4 / 972 (0.41%)
    4 / 948 (0.42%)
    3 / 758 (0.40%)
         occurrences causally related to treatment / all
    4 / 4
    4 / 4
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    Rectal ulcer haemorrhage
         subjects affected / exposed
    0 / 972 (0.00%)
    0 / 948 (0.00%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Retroperitoneal haematoma
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Small intestinal obstruction
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Stomach mass
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Upper gastrointestinal haemorrhage
         subjects affected / exposed
    0 / 972 (0.00%)
    2 / 948 (0.21%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Bile duct obstruction
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Biliary cirrhosis primary
         subjects affected / exposed
    0 / 972 (0.00%)
    0 / 948 (0.00%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Biliary colic
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cholecystitis
         subjects affected / exposed
    4 / 972 (0.41%)
    4 / 948 (0.42%)
    2 / 758 (0.26%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 4
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cholecystitis acute
         subjects affected / exposed
    2 / 972 (0.21%)
    1 / 948 (0.11%)
    2 / 758 (0.26%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Cholelithiasis
         subjects affected / exposed
    4 / 972 (0.41%)
    3 / 948 (0.32%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Drug-induced liver injury
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gallbladder perforation
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatic cirrhosis
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatic failure
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatitis toxic
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatomegaly
         subjects affected / exposed
    0 / 972 (0.00%)
    0 / 948 (0.00%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Dermatitis
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dermatitis allergic
         subjects affected / exposed
    0 / 972 (0.00%)
    0 / 948 (0.00%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diabetic foot
         subjects affected / exposed
    1 / 972 (0.10%)
    2 / 948 (0.21%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haemorrhage subcutaneous
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pemphigoid
         subjects affected / exposed
    0 / 972 (0.00%)
    0 / 948 (0.00%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Psoriasis
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Skin ulcer
         subjects affected / exposed
    1 / 972 (0.10%)
    1 / 948 (0.11%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Stasis dermatitis
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    15 / 972 (1.54%)
    6 / 948 (0.63%)
    14 / 758 (1.85%)
         occurrences causally related to treatment / all
    2 / 15
    0 / 6
    1 / 18
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Acute prerenal failure
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Calculus bladder
         subjects affected / exposed
    0 / 972 (0.00%)
    0 / 948 (0.00%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Chronic kidney disease
         subjects affected / exposed
    1 / 972 (0.10%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cystitis haemorrhagic
         subjects affected / exposed
    0 / 972 (0.00%)
    2 / 948 (0.21%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haematuria
         subjects affected / exposed
    3 / 972 (0.31%)
    7 / 948 (0.74%)
    4 / 758 (0.53%)
         occurrences causally related to treatment / all
    2 / 3
    7 / 7
    4 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haemorrhage urinary tract
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nephrolithiasis
         subjects affected / exposed
    1 / 972 (0.10%)
    1 / 948 (0.11%)
    3 / 758 (0.40%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal cyst
         subjects affected / exposed
    0 / 972 (0.00%)
    0 / 948 (0.00%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal failure
         subjects affected / exposed
    6 / 972 (0.62%)
    2 / 948 (0.21%)
    3 / 758 (0.40%)
         occurrences causally related to treatment / all
    1 / 6
    0 / 3
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal impairment
         subjects affected / exposed
    3 / 972 (0.31%)
    1 / 948 (0.11%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    1 / 3
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal infarct
         subjects affected / exposed
    0 / 972 (0.00%)
    0 / 948 (0.00%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal mass
         subjects affected / exposed
    0 / 972 (0.00%)
    0 / 948 (0.00%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Urinary bladder haemorrhage
         subjects affected / exposed
    0 / 972 (0.00%)
    0 / 948 (0.00%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Urinary tract obstruction
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Endocrine disorders
    Thyroid mass
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    0 / 972 (0.00%)
    2 / 948 (0.21%)
    3 / 758 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Arthritis
         subjects affected / exposed
    0 / 972 (0.00%)
    0 / 948 (0.00%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bursitis
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Chondropathy
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Exostosis
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haemarthrosis
         subjects affected / exposed
    0 / 972 (0.00%)
    3 / 948 (0.32%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    3 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Intervertebral disc protrusion
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Joint swelling
         subjects affected / exposed
    0 / 972 (0.00%)
    0 / 948 (0.00%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Muscle haemorrhage
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal chest pain
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal pain
         subjects affected / exposed
    1 / 972 (0.10%)
    2 / 948 (0.21%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Myalgia
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Osteoarthritis
         subjects affected / exposed
    7 / 972 (0.72%)
    2 / 948 (0.21%)
    4 / 758 (0.53%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 2
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Osteochondrosis
         subjects affected / exposed
    0 / 972 (0.00%)
    0 / 948 (0.00%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Plica syndrome
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Polymyalgia rheumatica
         subjects affected / exposed
    1 / 972 (0.10%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Rheumatoid arthritis
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Rotator cuff syndrome
         subjects affected / exposed
    0 / 972 (0.00%)
    0 / 948 (0.00%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Sacroiliitis
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Spinal column stenosis
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    2 / 758 (0.26%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Anal abscess
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Appendicitis
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bone abscess
         subjects affected / exposed
    0 / 972 (0.00%)
    0 / 948 (0.00%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bronchiolitis
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bronchitis
         subjects affected / exposed
    2 / 972 (0.21%)
    2 / 948 (0.21%)
    2 / 758 (0.26%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Candida infection
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    1 / 972 (0.10%)
    3 / 948 (0.32%)
    6 / 758 (0.79%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cytomegalovirus infection
         subjects affected / exposed
    0 / 972 (0.00%)
    0 / 948 (0.00%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dengue fever
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Device related infection
         subjects affected / exposed
    2 / 972 (0.21%)
    0 / 948 (0.00%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diabetic foot infection
         subjects affected / exposed
    0 / 972 (0.00%)
    0 / 948 (0.00%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diverticulitis intestinal haemorrhagic
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Empyema
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Endocarditis
         subjects affected / exposed
    2 / 972 (0.21%)
    0 / 948 (0.00%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Epididymitis
         subjects affected / exposed
    0 / 972 (0.00%)
    0 / 948 (0.00%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Escherichia sepsis
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Erysipelas
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    2 / 758 (0.26%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Fungal oesophagitis
         subjects affected / exposed
    0 / 972 (0.00%)
    0 / 948 (0.00%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gangrene
         subjects affected / exposed
    2 / 972 (0.21%)
    0 / 948 (0.00%)
    2 / 758 (0.26%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastritis viral
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    1 / 972 (0.10%)
    1 / 948 (0.11%)
    2 / 758 (0.26%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatitis C
         subjects affected / exposed
    0 / 972 (0.00%)
    0 / 948 (0.00%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Helicobacter infection
         subjects affected / exposed
    0 / 972 (0.00%)
    0 / 948 (0.00%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infected cyst
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infection
         subjects affected / exposed
    1 / 972 (0.10%)
    2 / 948 (0.21%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infectious pleural effusion
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infective exacerbation of chronic obstructive airways disease
         subjects affected / exposed
    0 / 972 (0.00%)
    0 / 948 (0.00%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Influenza
         subjects affected / exposed
    2 / 972 (0.21%)
    3 / 948 (0.32%)
    3 / 758 (0.40%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Labyrinthitis
         subjects affected / exposed
    0 / 972 (0.00%)
    0 / 948 (0.00%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Liver abscess
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lower respiratory tract infection
         subjects affected / exposed
    1 / 972 (0.10%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lung infection
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    2 / 758 (0.26%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Orchitis
         subjects affected / exposed
    1 / 972 (0.10%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Osteomyelitis
         subjects affected / exposed
    3 / 972 (0.31%)
    0 / 948 (0.00%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pharyngitis
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    20 / 972 (2.06%)
    19 / 948 (2.00%)
    15 / 758 (1.98%)
         occurrences causally related to treatment / all
    0 / 22
    0 / 19
    1 / 19
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonia bacterial
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonia mycoplasmal
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pseudomonas infection
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pulmonary sepsis
         subjects affected / exposed
    0 / 972 (0.00%)
    2 / 948 (0.21%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pyelonephritis
         subjects affected / exposed
    0 / 972 (0.00%)
    0 / 948 (0.00%)
    2 / 758 (0.26%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pyelonephritis acute
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal abscess
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory tract infection
         subjects affected / exposed
    2 / 972 (0.21%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory tract infection viral
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Rhinovirus infection
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Scrotal abscess
         subjects affected / exposed
    2 / 972 (0.21%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    5 / 972 (0.51%)
    4 / 948 (0.42%)
    5 / 758 (0.66%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 4
    1 / 5
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    Septic shock
         subjects affected / exposed
    0 / 972 (0.00%)
    2 / 948 (0.21%)
    3 / 758 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Skin bacterial infection
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Soft tissue infection
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Staphylococcal bacteraemia
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Staphylococcal sepsis
         subjects affected / exposed
    0 / 972 (0.00%)
    0 / 948 (0.00%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Systemic infection
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Upper respiratory tract infection
         subjects affected / exposed
    0 / 972 (0.00%)
    0 / 948 (0.00%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    6 / 972 (0.62%)
    4 / 948 (0.42%)
    3 / 758 (0.40%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 4
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection bacterial
         subjects affected / exposed
    0 / 972 (0.00%)
    0 / 948 (0.00%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Urosepsis
         subjects affected / exposed
    3 / 972 (0.31%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vestibular neuronitis
         subjects affected / exposed
    2 / 972 (0.21%)
    0 / 948 (0.00%)
    2 / 758 (0.26%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Viral infection
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    2 / 972 (0.21%)
    2 / 948 (0.21%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diabetes mellitus
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diabetes mellitus inadequate control
         subjects affected / exposed
    1 / 972 (0.10%)
    2 / 948 (0.21%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diabetic metabolic decompensation
         subjects affected / exposed
    1 / 972 (0.10%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gout
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hyperglycaemia
         subjects affected / exposed
    3 / 972 (0.31%)
    4 / 948 (0.42%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hyperhomocysteinaemia
         subjects affected / exposed
    0 / 972 (0.00%)
    0 / 948 (0.00%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hyperkalaemia
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    2 / 758 (0.26%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    Hypernatraemia
         subjects affected / exposed
    0 / 972 (0.00%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypoglycaemia
         subjects affected / exposed
    0 / 972 (0.00%)
    0 / 948 (0.00%)
    1 / 758 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypokalaemia
         subjects affected / exposed
    2 / 972 (0.21%)
    2 / 948 (0.21%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hyponatraemia
         subjects affected / exposed
    3 / 972 (0.31%)
    1 / 948 (0.11%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypovolaemia
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Metabolic disorder
         subjects affected / exposed
    0 / 972 (0.00%)
    2 / 948 (0.21%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Metabolic syndrome
         subjects affected / exposed
    1 / 972 (0.10%)
    0 / 948 (0.00%)
    0 / 758 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Dabigatran Etexilate 110mg Warfarin Dabigatran Etexilate 150mg
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    128 / 972 (13.17%)
    229 / 948 (24.16%)
    126 / 758 (16.62%)
    Vascular disorders
    Haematoma
         subjects affected / exposed
    27 / 972 (2.78%)
    60 / 948 (6.33%)
    24 / 758 (3.17%)
         occurrences all number
    30
    74
    28
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    62 / 972 (6.38%)
    61 / 948 (6.43%)
    60 / 758 (7.92%)
         occurrences all number
    80
    89
    77
    Epistaxis
         subjects affected / exposed
    52 / 972 (5.35%)
    146 / 948 (15.40%)
    59 / 758 (7.78%)
         occurrences all number
    71
    218
    81

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    16 Sep 2015
    This amendment introduced several changes to facilitate patient recruitment and to operationally simplify trial procedures. The time windows for Visit 1 and for drug administration post PCI were prolonged (Visit 1 prolonged by 2 d and first drug administration prolonged by 48 h to a maximum of 120 h after PCI). It was allowed to use of blood samples taken by standard of care local laboratory up to 7 d prior to screening to verify eligibility. The physical examination was streamlined. A possibility to switch the antiplatelet therapy to ASA (≤100 mg once daily) after Month 12 as per investigator discretion was introduced as well. Inclusion/exclusion criteria were modified to allow inclusion of patients with atrial fibrillation secondary to a reversible disorder if they were candidates for long term oral anticoagulation; patients on cytotoxic/myelosuppresive therapy were no longer excluded. A clarification regarding the definition of active liver disease was added to the exclusion criterion 13. The use of the reversal agent for dabigatran was introduced as well as the allowance to collect the information regarding its use. The restriction of ASA use during the on-treatment period and recording of concomitant therapy throughout the trial were clarified. Subclassifications of myocardial infarction were introduced and the definitions of fatal and disabling stoke were added. Finally, the need for monitoring of drug-induced liver injury (AESIs) was removed as there were no signs of dabigatran-related hepatotoxicity during the clinical development and post-marketing period.
    05 Apr 2016
    This amendment revised the trial design due to insufficient patient recruitment rate. The trial focused on safety and was powered to test the non-inferiority of each of the dabigatran etexilate doses (110 mg and 150 mg bid) in a dual antithrombotic regimen versus warfarin in a triple antithrombotic regimen in respect to bleeding events (time to first ISTH major bleeding or clinically relevant non-major bleeding event). Efficacy parameters (e.g. all death, myocardial infarction, stroke/systemic embolism), including the original co-primary endpoint (DTE), were to be evaluated as secondary endpoints. A definition of unplanned revascularisation was added as well. Regarding hypothesis testing, a hierarchical approach replaced the original Benjamini-Hochberg procedure as the Type I error rate control method. The change of trial design led to the reduction of total number of entered patients from 8520 to 2502 and from 2840 entered patients per treatment arm to 834. Moreover, an unblinded interim analysis was removed to reflect the changes in trial design. Following the changes introduced by Global Amendment 1, the guideline on using the reversal agent was updated to reflect current approval status of idarucizumab. Finally, the amendment introduced that warfarin tablets were also supplied as blister packs.
    21 Jul 2016
    This amendment introduced that repeated revascularisation by PCI/CABG had to be adjudicated by the IAC as requested by the DMC. This change in administrative aspect did not require approval by the IRB/IEC/competent authority.

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    1 subject with missing information for number of enrolled subjects has been included in age range 'Elderly 85 years and over' as the missing category is not available.
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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