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    Clinical Trial Results:
    An OPen-label, Randomized, Controlled, Multicenter Study ExplorIng TwO TreatmeNt StratEgiEs of Rivaroxaban and a Dose-Adjusted Oral Vitamin K Antagonist Treatment Strategy in Subjects With Atrial Fibrillation Who Undergo Percutaneous Coronary Intervention

    Summary
    EudraCT number
    		 2012-001491-11
    Trial protocol
    		 DE   BE   GB   SE   IT   NL   DK   PL   BG   CZ  
    Global end of trial date
    28 Jul 2016

    Results information
    Results version number
    		 v1(current)
    This version publication date
    16 Jul 2017
    First version publication date
    16 Jul 2017
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    RIVAROXAFL3003
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01830543
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Janssen Scientific Affairs, LLC
    Sponsor organisation address
    1125 Trenton-Harbourton Road, Titusville, NJ , United States, 08560
    Public contact
    Clinical Registry group, Janssen Scientific Affairs, LLC, ClinicalTrialsEU@its.jnj.com
    Scientific contact
    Clinical Registry group, Janssen Scientific Affairs, LLC, ClinicalTrialsEU@its.jnj.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
    28 Jul 2016
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    28 Jul 2016
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective of this study was to assess the safety of 2 rivaroxaban treatment strategies and a dose-adjusted vitamin K antagonist (VKA) treatment strategy after percutaneous coronary intervention (PCI) (with stent placement) in subjects with paroxysmal, persistent, or permanent non-valvular atrial fibrillation (AF), based on the composite of Thrombolysis in Myocardial Infarction (TIMI) major bleeding, minor bleeding, and bleeding requiring medical attention events (known collectively as clinically significant bleeding) after 12 months of therapy.
    Protection of trial subjects
    Safety was evaluated throughout the study and included monitoring of clinical events (cardiovascular (CV) death, myocardial infarction (MI), stroke, bleeding events, and stent thrombosis) and adverse events (AEs), and performing clinical laboratory tests (hematology, serum chemistry, and international normalized ratio [INR]) bleeding event assessment and classification.This study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and that are consistent with Good Clinical Practices (GCPs) and applicable regulatory requirements.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    10 May 2013
    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: 82
    Country: Number of subjects enrolled
    Australia: 15
    Country: Number of subjects enrolled
    Belgium: 52
    Country: Number of subjects enrolled
    Brazil: 41
    Country: Number of subjects enrolled
    Bulgaria: 221
    Country: Number of subjects enrolled
    Canada: 66
    Country: Number of subjects enrolled
    Chile: 18
    Country: Number of subjects enrolled
    Czech Republic: 40
    Country: Number of subjects enrolled
    Denmark: 12
    Country: Number of subjects enrolled
    France: 84
    Country: Number of subjects enrolled
    Germany: 295
    Country: Number of subjects enrolled
    Italy: 72
    Country: Number of subjects enrolled
    Malaysia: 11
    Country: Number of subjects enrolled
    Mexico: 13
    Country: Number of subjects enrolled
    Netherlands: 68
    Country: Number of subjects enrolled
    Poland: 218
    Country: Number of subjects enrolled
    Korea, Republic of: 39
    Country: Number of subjects enrolled
    Romania: 50
    Country: Number of subjects enrolled
    Russian Federation: 265
    Country: Number of subjects enrolled
    South Africa: 5
    Country: Number of subjects enrolled
    Sweden: 47
    Country: Number of subjects enrolled
    Taiwan: 25
    Country: Number of subjects enrolled
    Turkey: 43
    Country: Number of subjects enrolled
    Ukraine: 60
    Country: Number of subjects enrolled
    United Kingdom: 131
    Country: Number of subjects enrolled
    United States: 151
    Worldwide total number of subjects
    2124
    EEA total number of subjects
    1290
    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)
    559
    From 65 to 84 years
    1479
    85 years and over
    86

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 A total of 2,124 subjects were randomized out of which 2,099 received at least 1 dose of study agent and 1,599 completed the treatment period.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Rivaroxaban 15 milligram (mg)
    Arm description
    		 Subjects received rivaroxaban 15 mg or 10 mg (for subjects with moderate renal impairment [creatinine clearance (CrCl): 30 to less than (<) 50 milliliter per minute (mL/min)]) once daily plus background therapy with clopidogrel 75 mg once daily or alternate P2Y12 inhibitor (prasugrel 10 mg per day or ticagrelor 90 mg twice daily) for 12 months.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Rivaroxaban
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received rivaroxaban 15 mg tablet (or 10 mg for subjects with moderate renal impairment [CrCl: 30 to <50 mL/min]) once daily for 12 months.

    Investigational medicinal product name
    Clopidogrel
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received clopidogrel 75 mg tablet daily as background therapy for 12 months.

    Investigational medicinal product name
    Prasugrel
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received prasugrel 10 mg tablet per day as background therapy for 12 months.

    Investigational medicinal product name
    Ticagrelor
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received ticagrelor 90 mg tablet twice daily as background therapy for 12 months.

    Arm title
    		 Rivaroxaban 2.5 mg Twice Daily (BID)/15 mg Once Daily(QD)
    Arm description
    		 Subjects received rivaroxaban 2.5 mg twice daily plus background dual antiplatelet therapy (DAPT) with low dose acetylsalicylic acid (ASA) 75 to 100 mg per day and clopidogrel 75 mg once daily (or alternate P2Y12 inhibitor [prasugrel or ticagrelor]) for an intended DAPT duration of 1, 6, or 12 months. Only subjects with an intended DAPT duration of 1 or 6-month transitioned to receive rivaroxaban 15 mg or 10 mg (for subjects with moderate renal impairment) once daily plus background single antiplatelet therapy with low dose ASA for the rest of the period up to Month 12.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Rivaroxaban 2.5 mg
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received rivaroxaban 2.5 mg tablet twice daily for 1, 6 or 12 months.

    Investigational medicinal product name
    Clopidogrel
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received clopidogrel 75 mg tablet daily as background therapy for 1, 6 or 12 months.

    Investigational medicinal product name
    Prasugrel
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received prasugrel 10 mg tablet per day as background therapy for 1, 6 or 12 months.

    Investigational medicinal product name
    Ticagrelor
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received ticagrelor 90 mg tablet twice daily as background therapy for 1, 6 or 12 months.

    Investigational medicinal product name
    Acetylsalicylic acid
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received low-dose of acetyl salicylic acid 75 to 100 mg tablet daily for 1, 6 or 12 months.

    Investigational medicinal product name
    Rivaroxaban 15 mg
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects with an intended DAPT duration of 1 or 6-month transitioned to receive rivaroxaban 15 mg once daily plus background single antiplatelet therapy with low dose ASA for the rest of the period up to Month 12.

    Investigational medicinal product name
    Rivaroxaban 10 mg
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects with an intended DAPT duration of 1 or 6-month transitioned to receive rivaroxaban 10 mg (for subjects with moderate renal impairment) once daily plus background single antiplatelet therapy with low dose ASA for the rest of the period up to Month 12.

    Arm title
    		 Vitamin K antagonist (VKA)
    Arm description
    		 Subjects received dose adjusted (to a target of international normalized ratio [INR] 2.0 to 3.0 [or target INR 2.0 to 2.5]) vitamin K antagonist (VKA) [eg, warfarin, acenocoumarol; assigned by the investigator according to approved formulations) once daily plus background DAPT (clopidogrel 75 mg [or alternate P2Y12 inhibitor (prasugrel or ticagrelor)] plus low dose ASA [75 to 100 mg] daily) for an intended DAPT duration of 1, 6, or 12 months. Only subjects with an intended DAPT duration of 1 or 6-month transitioned to receive dose adjusted VKA plus background single antiplatelet therapy with low dose ASA for the rest of the period up to Month 12.
    Arm type
    		 Experimental

    Investigational medicinal product name
    warfarin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects recieved a single oral dose of warfarin adjusted (to a target of [INR] 2.0 to 3.0 [or target INR 2.0 to 2.5]) once daily for 1, 6 or 12 months.

    Investigational medicinal product name
    Acenocoumarol
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects recieved a single oral dose of acenocoumarol adjusted (to a target of [INR] 2.0 to 3.0 [or target INR 2.0 to 2.5]) once daily for 1, 6 or 12 months.

    Investigational medicinal product name
    Clopidogrel
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received clopidogrel 75 mg tablet daily as background therapy for 1, 6 or 12 months.

    Investigational medicinal product name
    Ticagrelor
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received ticagrelor 90 mg tablet twice daily as background therapy for 1, 6 or 12 months.

    Investigational medicinal product name
    Prasugrel
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received prasugrel 10 mg tablet per day as background therapy for 1, 6 or 12 months.

    Investigational medicinal product name
    Acetylsalicylic acid
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received low-dose of acetyl salicylic acid 75 to 100 mg tablet daily for 1, 6 or 12 months.

    Number of subjects in period 1
    		Rivaroxaban 15 milligram (mg) Rivaroxaban 2.5 mg Twice Daily (BID)/15 mg Once Daily(QD) Vitamin K antagonist (VKA)
    Started
    709
    709
    706
    Treated
    696
    706
    697
    Completed
    550
    557
    492
    Not completed
    159
    152
    214
         Consent withdrawn by subject
    3
    3
    3
         Physician decision
    11
    5
    12
         Subject Decision
    19
    21
    57
         Death
    20
    22
    22
         Adverse event
    91
    77
    76
         Unspecified
    12
    17
    37
         Protocol deviation
    3
    7
    7

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Rivaroxaban 15 milligram (mg)
    Reporting group description
    		 Subjects received rivaroxaban 15 mg or 10 mg (for subjects with moderate renal impairment [creatinine clearance (CrCl): 30 to less than (<) 50 milliliter per minute (mL/min)]) once daily plus background therapy with clopidogrel 75 mg once daily or alternate P2Y12 inhibitor (prasugrel 10 mg per day or ticagrelor 90 mg twice daily) for 12 months.

    Reporting group title
    Rivaroxaban 2.5 mg Twice Daily (BID)/15 mg Once Daily(QD)
    Reporting group description
    		 Subjects received rivaroxaban 2.5 mg twice daily plus background dual antiplatelet therapy (DAPT) with low dose acetylsalicylic acid (ASA) 75 to 100 mg per day and clopidogrel 75 mg once daily (or alternate P2Y12 inhibitor [prasugrel or ticagrelor]) for an intended DAPT duration of 1, 6, or 12 months. Only subjects with an intended DAPT duration of 1 or 6-month transitioned to receive rivaroxaban 15 mg or 10 mg (for subjects with moderate renal impairment) once daily plus background single antiplatelet therapy with low dose ASA for the rest of the period up to Month 12.

    Reporting group title
    Vitamin K antagonist (VKA)
    Reporting group description
    		 Subjects received dose adjusted (to a target of international normalized ratio [INR] 2.0 to 3.0 [or target INR 2.0 to 2.5]) vitamin K antagonist (VKA) [eg, warfarin, acenocoumarol; assigned by the investigator according to approved formulations) once daily plus background DAPT (clopidogrel 75 mg [or alternate P2Y12 inhibitor (prasugrel or ticagrelor)] plus low dose ASA [75 to 100 mg] daily) for an intended DAPT duration of 1, 6, or 12 months. Only subjects with an intended DAPT duration of 1 or 6-month transitioned to receive dose adjusted VKA plus background single antiplatelet therapy with low dose ASA for the rest of the period up to Month 12.

    Reporting group values
    		 Rivaroxaban 15 milligram (mg) Rivaroxaban 2.5 mg Twice Daily (BID)/15 mg Once Daily(QD) Vitamin K antagonist (VKA) Total
    Number of subjects
    		 709 709 706 2124
    Title for AgeCategorical
    Units: subjects
        Children (2-11 years)
    		 0 0 0 0
        Adolescents (12-17 years)
    		 0 0 0 0
        Adults (18-64 years)
    		 186 193 180 559
        From 65 to 84 years
    		 489 488 502 1479
        85 years and over
    		 34 28 24 86
    Title for AgeContinuous
    Units: years
        arithmetic mean (standard deviation)
    		 70.4 ( 9.12 ) 70 ( 9.11 ) 69.9 ( 8.67 ) -
    Title for Gender
    Units: subjects
        Female
    		 181 174 188 543
        Male
    		 528 535 518 1581

    End points

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    End points reporting groups
    Reporting group title
    Rivaroxaban 15 milligram (mg)
    Reporting group description
    		 Subjects received rivaroxaban 15 mg or 10 mg (for subjects with moderate renal impairment [creatinine clearance (CrCl): 30 to less than (<) 50 milliliter per minute (mL/min)]) once daily plus background therapy with clopidogrel 75 mg once daily or alternate P2Y12 inhibitor (prasugrel 10 mg per day or ticagrelor 90 mg twice daily) for 12 months.

    Reporting group title
    Rivaroxaban 2.5 mg Twice Daily (BID)/15 mg Once Daily(QD)
    Reporting group description
    		 Subjects received rivaroxaban 2.5 mg twice daily plus background dual antiplatelet therapy (DAPT) with low dose acetylsalicylic acid (ASA) 75 to 100 mg per day and clopidogrel 75 mg once daily (or alternate P2Y12 inhibitor [prasugrel or ticagrelor]) for an intended DAPT duration of 1, 6, or 12 months. Only subjects with an intended DAPT duration of 1 or 6-month transitioned to receive rivaroxaban 15 mg or 10 mg (for subjects with moderate renal impairment) once daily plus background single antiplatelet therapy with low dose ASA for the rest of the period up to Month 12.

    Reporting group title
    Vitamin K antagonist (VKA)
    Reporting group description
    		 Subjects received dose adjusted (to a target of international normalized ratio [INR] 2.0 to 3.0 [or target INR 2.0 to 2.5]) vitamin K antagonist (VKA) [eg, warfarin, acenocoumarol; assigned by the investigator according to approved formulations) once daily plus background DAPT (clopidogrel 75 mg [or alternate P2Y12 inhibitor (prasugrel or ticagrelor)] plus low dose ASA [75 to 100 mg] daily) for an intended DAPT duration of 1, 6, or 12 months. Only subjects with an intended DAPT duration of 1 or 6-month transitioned to receive dose adjusted VKA plus background single antiplatelet therapy with low dose ASA for the rest of the period up to Month 12.

    Primary: Percentage of Subjects With Clinically Significant Bleeding

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    End point title
    		 Percentage of Subjects With Clinically Significant Bleeding
    End point description
    Clinically significant bleeding is a composite of TIMI major bleeding, minor bleeding, and BRMA. TIMI major bleeding is defined as any symptomatic intracranial hemorrhage, clinically overt signs of hemorrhage (including imaging) associated with a drop in hemoglobin of greater than or equal to (>=) 5 g/dL (or when the hemoglobin concentration is not available, an absolute drop in hematocrit of >=15 percent). TIMI minor bleeding event is defined as any clinically overt sign of hemorrhage (including imaging) that is associated with a fall in hemoglobin concentration of 3 to less than (<)5 g/dL (or, when hemoglobin concentration is not available, a fall in hematocrit of 9 percent to <15 percent). A BRMA event is defined as any bleeding event that requires medical treatment, surgical treatment, or laboratory evaluation, and does not meet criteria for a major or minor bleeding event. The Safety Analysis Set is defined as all randomized subjects who received at least 1 dose of study drug.
    End point type
    Primary
    End point timeframe
    Up to Month 12
    End point values
    		 Rivaroxaban 15 milligram (mg) Rivaroxaban 2.5 mg Twice Daily (BID)/15 mg Once Daily(QD) Vitamin K antagonist (VKA)
    Number of subjects analysed
    696
    706
    697
    Units: percentage of subjects
        number (not applicable)
    15.7
    16.6
    24
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Rivaroxaban 15 milligram (mg) v Vitamin K antagonist (VKA)
    Number of subjects included in analysis
    1393
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.59
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.47
         upper limit
    		 0.76
    Statistical analysis title
    		 Statistical Analysis 2
    Comparison groups
    Rivaroxaban 2.5 mg Twice Daily (BID)/15 mg Once Daily(QD) v Vitamin K antagonist (VKA)
    Number of subjects included in analysis
    1403
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.63
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.5
         upper limit
    		 0.8

    Secondary: Percentage of Subjects With Thrombolysis in Myocardial Infarction (TIMI) Major Bleeding

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    End point title
    		 Percentage of Subjects With Thrombolysis in Myocardial Infarction (TIMI) Major Bleeding
    End point description
    TIMI major bleeding is defined as any symptomatic intracranial hemorrhage, Clinically overt signs of hemorrhage (including imaging) associated with a drop in hemoglobin of greater than or equal to (>=5) grams per deciliter (g/dL) (or when the hemoglobin concentration is not available, an absolute drop in hematocrit of >=15 percent). The Safety Analysis Set is defined as all randomized subjects who received at least 1 dose of study drug. Here, 'n' signifies number of subjects analyzed at specific time-point in this endpoint and '99999' signifies that no data was analysed in this endpoint for the specified arm as the analysis at end of DAPT-1, 6 and 12 month conducted only in subjects who received DAPT as part of therapy.
    End point type
    Secondary
    End point timeframe
    Up to Month 12 and end of DAPT-Month 1, 6 and 12
    End point values
    		 Rivaroxaban 15 milligram (mg) Rivaroxaban 2.5 mg Twice Daily (BID)/15 mg Once Daily(QD) Vitamin K antagonist (VKA)
    Number of subjects analysed
    696
    706
    697
    Units: Percentage of subjects
    number (not applicable)
        Up to Month 12 (n= 696, 706, 697)
    2
    1.7
    2.9
        End of DAPT-1 Month (n= 0, 108,113)
    99999
    0.9
    4.4
        End of DAPT-6 Month (n= 0, 248,243)
    99999
    2.8
    3.7
        End of DAPT-12 Month (n= 0,350,341)
    99999
    1.1
    1.8
    Statistical analysis title
    		 Statistical analysis 1
    Comparison groups
    Rivaroxaban 15 milligram (mg) v Vitamin K antagonist (VKA)
    Number of subjects included in analysis
    1393
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.234
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.66
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.33
         upper limit
    		 1.31
    Statistical analysis title
    		 Statistical analysis 2
    Comparison groups
    Rivaroxaban 2.5 mg Twice Daily (BID)/15 mg Once Daily(QD) v Vitamin K antagonist (VKA)
    Number of subjects included in analysis
    1403
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.114
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.57
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.28
         upper limit
    		 1.16

    Secondary: Percentage of Subjects With Thrombolysis in Myocardial Infarction (TIMI) Minor Bleeding

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    End point title
    		 Percentage of Subjects With Thrombolysis in Myocardial Infarction (TIMI) Minor Bleeding
    End point description
    TIMI minor bleeding event is defined as any clinically overt sign of hemorrhage (including imaging) that is associated with a fall in hemoglobin concentration of 3 to less than <5 g/dL (or, when hemoglobin concentration is not available, a fall in hematocrit of 9 percent to (<)15 percent). The Safety Analysis Set is defined as all randomized subjects who received at least 1 dose of study drug. Here 'n' signifies number of subjects analyzed at specific time-point in this endpoint and '99999' signifies that no data was analysed in this endpoint for the specified arm as the analysis at end of DAPT-1, 6 and 12 month conducted only in subjects who received DAPT as part of therapy.
    End point type
    Secondary
    End point timeframe
    Up to Month 12 and end of DAPT-Month 1, 6 and 12
    End point values
    		 Rivaroxaban 15 milligram (mg) Rivaroxaban 2.5 mg Twice Daily (BID)/15 mg Once Daily(QD) Vitamin K antagonist (VKA)
    Number of subjects analysed
    696
    706
    697
    Units: Percentage of subjects
    number (not applicable)
        Up to Month 12 (n= 696, 706, 697)
    1
    1
    1.9
        End of DAPT-1 Month (n= 0, 108, 113)
    99999
    0.9
    1.8
        End of DAPT-6 Month (n= 0, 248, 243)
    99999
    0.4
    2.5
        End of DAPT-12 Month (n= 0, 350, 341)
    99999
    1.4
    1.5
    Statistical analysis title
    		 Statistical analysis 1
    Comparison groups
    Rivaroxaban 15 milligram (mg) v Vitamin K antagonist (VKA)
    Number of subjects included in analysis
    1393
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.144
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.51
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.2
         upper limit
    		 1.28
    Statistical analysis title
    		 Statistical analysis 2
    Comparison groups
    Rivaroxaban 2.5 mg Twice Daily (BID)/15 mg Once Daily(QD) v Vitamin K antagonist (VKA)
    Number of subjects included in analysis
    1403
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.134
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.2
         upper limit
    		 1.26

    Secondary: Percentage of Subjects With Bleeding Requiring Medical Attention (BRMA)

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    End point title
    		 Percentage of Subjects With Bleeding Requiring Medical Attention (BRMA)
    End point description
    A BRMA event is defined as any bleeding event that requires medical treatment, surgical treatment, or laboratory evaluation, and does not meet criteria for a major or minor bleeding event. The Safety Analysis Set is defined as all randomized subjects who received at least 1 dose of study drug. Here 'n' signifies number of subjects analyzed at specific time-point in this endpoint and '99999' signifies that no data was analysed in this endpoint for the specified arm as the analysis at end of DAPT-1, 6 and 12 month conducted only in subjects who received DAPT as part of therapy.
    End point type
    Secondary
    End point timeframe
    Up to Month 12 and end of DAPT-Month 1, 6 and 12
    End point values
    		 Rivaroxaban 15 milligram (mg) Rivaroxaban 2.5 mg Twice Daily (BID)/15 mg Once Daily(QD) Vitamin K antagonist (VKA)
    Number of subjects analysed
    696
    706
    697
    Units: percentage of subjects
    number (not applicable)
        Up to Month 12 (n= 696, 706, 697)
    13.4
    14.4
    19.9
        End of DAPT-1 Month (n= 0, 108, 113)
    99999
    16.7
    18.6
        End of DAPT-6 Month (n= 0, 248, 243)
    99999
    12.9
    23
        End of DAPT-12 Month (n= 0, 350, 341)
    99999
    14.9
    18.2
    Statistical analysis title
    		 Statistical analysis 1
    Comparison groups
    Rivaroxaban 15 milligram (mg) v Vitamin K antagonist (VKA)
    Number of subjects included in analysis
    1393
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.61
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.47
         upper limit
    		 0.8
    Statistical analysis title
    		 Statistical analysis 2
    Comparison groups
    Rivaroxaban 2.5 mg Twice Daily (BID)/15 mg Once Daily(QD) v Vitamin K antagonist (VKA)
    Number of subjects included in analysis
    1403
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.002
    Method
    		 Logrank
    Parameter type
    		 Log hazard ratio
    Point estimate
    0.67
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.52
         upper limit
    		 0.86

    Secondary: Percentage of Subjects With Composite of Adverse Cardiovascular Events (Cardiovascular Death, Myocardial Infarction (MI) and Stroke)

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    End point title
    		 Percentage of Subjects With Composite of Adverse Cardiovascular Events (Cardiovascular Death, Myocardial Infarction (MI) and Stroke)
    End point description
    Percentage of subjects who experienced adverse cardiovascular events (Cardiovascular Death, Myocardial Infarction (MI) and Stroke) collectively, were assessed. The Safety Analysis Set is defined as all randomized subjects who received at least 1 dose of study drug. Here 'N' signifies number of subjects who were evaluable for this outcome measure, 'n' signifies number of subjects analyzed at specific time-point in this endpoint. Here '99999' signifies that no data was analysed in this endpoint for the specified arm as the analysis at end of DAPT-1, 6 and 12 month conducted only in subjects who received DAPT as part of therapy.
    End point type
    Secondary
    End point timeframe
    Up to Month 12 and end of DAPT-month 1, 6 and 12
    End point values
    		 Rivaroxaban 15 milligram (mg) Rivaroxaban 2.5 mg Twice Daily (BID)/15 mg Once Daily(QD) Vitamin K antagonist (VKA)
    Number of subjects analysed
    694
    704
    695
    Units: Percentage of subjects
    number (not applicable)
        Up to Month 12 (n= 694, 704, 695)
    5.9
    5.1
    5.2
        End of DAPT-1 Month (n= 0, 108, 112)
    99999
    5.6
    4.5
        End of DAPT-6 Month (n= 0, 248, 243)
    99999
    6.5
    3.7
        End of DAPT-12 Month (n= 0, 348, 340)
    99999
    4
    6.5
    Statistical analysis title
    		 Statistical analysis 1
    Comparison groups
    Rivaroxaban 15 milligram (mg) v Vitamin K antagonist (VKA)
    Number of subjects included in analysis
    1389
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.75
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.08
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.69
         upper limit
    		 1.68
    Statistical analysis title
    		 Statistical analysis 2
    Comparison groups
    Rivaroxaban 2.5 mg Twice Daily (BID)/15 mg Once Daily(QD) v Vitamin K antagonist (VKA)
    Number of subjects included in analysis
    1399
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.765
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.93
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.59
         upper limit
    		 1.48

    Secondary: Percentage of Subjects With Cardiovascular Death

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    End point title
    		 Percentage of Subjects With Cardiovascular Death
    End point description
    The percentage of subjects with the first occurrence of cardiovascular death were evaluated. The Safety Analysis Set is defined as all randomized subjects who received at least 1 dose of study drug.Here 'N' signifies number of subjects who were evaluable for this outcome measure, 'n' signifies number of subjects analyzed at specific time-point in this endpoint and '99999' signifies that no data was analysed in this endpoint for the specified category as the analysis at end of DAPT-1, 6 and 12 month conducted only in subjects who received DAPT as part of therapy.
    End point type
    Secondary
    End point timeframe
    Up to Month 12 and end of DAPT-month 1, 6 and 12
    End point values
    		 Rivaroxaban 15 milligram (mg) Rivaroxaban 2.5 mg Twice Daily (BID)/15 mg Once Daily(QD) Vitamin K antagonist (VKA)
    Number of subjects analysed
    694
    704
    695
    Units: percentage of subjects
    number (not applicable)
        Up to Month 12 (n= 694, 704, 695)
    2.2
    2
    1.6
        End of DAPT-1 Month (n= 0, 108, 112)
    99999
    1.9
    1.8
        End of DAPT-6 Month (n= 0, 248, 243)
    99999
    2.4
    1.6
        End of DAPT-12 Month (n= 0, 348, 340)
    99999
    1.7
    1.5
    Statistical analysis title
    		 Statistical analysis 1
    Comparison groups
    Rivaroxaban 15 milligram (mg) v Vitamin K antagonist (VKA)
    Number of subjects included in analysis
    1389
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.523
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.29
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.59
         upper limit
    		 2.8
    Statistical analysis title
    		 Statistical analysis 2
    Comparison groups
    Rivaroxaban 2.5 mg Twice Daily (BID)/15 mg Once Daily(QD) v Vitamin K antagonist (VKA)
    Number of subjects included in analysis
    1399
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.664
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.19
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.54
         upper limit
    		 2.62

    Secondary: Percentage of Subjects With Myocardial Infarction

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    End point title
    		 Percentage of Subjects With Myocardial Infarction
    End point description
    The percentage of subjects with the first occurrence of the myocardial infarction were evaluated. The Safety Analysis Set is defined as all randomized subjects who received at least 1 dose of study drug. Here 'N' signifies number of subjects who were evaluable for this outcome measure, 'n' signifies number of subjects analyzed at specific time-point in this endpoint and '99999' signifies that no data was analysed in this endpoint for the specified category as the analysis at end of DAPT-1, 6 and 12 month conducted only in subjects who received DAPT as part of therapy.
    End point type
    Secondary
    End point timeframe
    Up to Month 12 and end of DAPT-Month 1, 6 and 12
    End point values
    		 Rivaroxaban 15 milligram (mg) Rivaroxaban 2.5 mg Twice Daily (BID)/15 mg Once Daily(QD) Vitamin K antagonist (VKA)
    Number of subjects analysed
    694
    704
    695
    Units: percentage of subjects
    number (not applicable)
        Up to Month 12 (n= 694, 704, 695)
    2.7
    2.4
    3
        End of DAPT-1 Month (n= 0, 108, 112)
    99999
    2.8
    0.9
        End of DAPT-6 Month (n= 0, 248, 243)
    99999
    2.8
    2.5
        End of DAPT-12 Month (n= 0, 348, 340)
    99999
    2
    4.1
    Statistical analysis title
    		 Statistical analysis 1
    Comparison groups
    Rivaroxaban 15 milligram (mg) v Vitamin K antagonist (VKA)
    Number of subjects included in analysis
    1389
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.625
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.86
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.46
         upper limit
    		 1.59
    Statistical analysis title
    		 Statistical analysis 2
    Comparison groups
    Rivaroxaban 2.5 mg Twice Daily (BID)/15 mg Once Daily(QD) v Vitamin K antagonist (VKA)
    Number of subjects included in analysis
    1399
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.374
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.75
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.4
         upper limit
    		 1.42

    Secondary: Percentage of Subjects With Stroke

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    End point title
    		 Percentage of Subjects With Stroke
    End point description
    The percentage of subjects with the first occurrence of stroke were evaluated. The Safety Analysis Set is defined as all randomized subjects who received at least 1 dose of study drug.Here 'N' signifies number of subjects who were evaluable for this outcome measure, 'n' signifies number of subjects analyzed at specific time-point in this endpoint and '99999' signifies that no data was analysed in this endpoint for the specified category as the analysis at end of DAPT-1, 6 and 12 month conducted only in subjects who received DAPT as part of therapy.
    End point type
    Secondary
    End point timeframe
    Up to Month 12 and end of DAPT-Month 1, 6 and 12
    End point values
    		 Rivaroxaban 15 milligram (mg) Rivaroxaban 2.5 mg Twice Daily (BID)/15 mg Once Daily(QD) Vitamin K antagonist (VKA)
    Number of subjects analysed
    694
    704
    695
    Units: percentage of subjects
    number (not applicable)
        Up to Month 12 (n= 694, 704, 695)
    1.2
    1.4
    1
        End of DAPT-1 Month (n= 0, 108, 112)
    99999
    1.9
    2.7
        End of DAPT-6 Month (n= 0, 248, 243)
    99999
    2.4
    0
        End of DAPT-12 Month (n= 0, 348, 340)
    99999
    0.6
    1.2
    Statistical analysis title
    		 Statistical analysis 1
    Comparison groups
    Rivaroxaban 15 milligram (mg) v Vitamin K antagonist (VKA)
    Number of subjects included in analysis
    1389
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.891
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.07
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.39
         upper limit
    		 2.96
    Statistical analysis title
    		 Statistical analysis 2
    Comparison groups
    Rivaroxaban 2.5 mg Twice Daily (BID)/15 mg Once Daily(QD) v Vitamin K antagonist (VKA)
    Number of subjects included in analysis
    1399
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.53
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.36
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.52
         upper limit
    		 3.58

    Secondary: Percentage of Subjects With Stent Thrombosis

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    End point title
    		 Percentage of Subjects With Stent Thrombosis
    End point description
    The percentage of subjects with the first occurrence of the stent thrombosis were evaluated. The Safety Analysis Set is defined as all randomized subjects who received at least 1 dose of study drug. Here 'N' signifies number of subjects who were evaluable for this outcome measure, 'n' signifies number of subjects analyzed at specific time-point in this outcome measureand '99999' signifies that no data was analysed in this endpoint for the specified category as the analysis at end of DAPT-1, 6 and 12 month conducted only in subjects who received DAPT as part of therapy.
    End point type
    Secondary
    End point timeframe
    Up to Month 12 and end of DAPT-month 1, 6 and 12
    End point values
    		 Rivaroxaban 15 milligram (mg) Rivaroxaban 2.5 mg Twice Daily (BID)/15 mg Once Daily(QD) Vitamin K antagonist (VKA)
    Number of subjects analysed
    694
    704
    695
    Units: percentage of subjects
    number (not applicable)
        Up to Month 12 (n= 694, 704, 695)
    0.7
    0.9
    0.6
        End of DAPT-1 Month (n= 0, 108, 112)
    99999
    1.9
    0.9
        End of DAPT-6 Month (n= 0, 248, 243)
    99999
    1.6
    0.4
        End of DAPT-12 Month (n= 0, 348, 340)
    99999
    0
    0.6
    Statistical analysis title
    		 Statistical analysis 1
    Comparison groups
    Rivaroxaban 15 milligram (mg) v Vitamin K antagonist (VKA)
    Number of subjects included in analysis
    1389
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.79
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.32
         upper limit
    		 4.45
    Statistical analysis title
    		 Statistical analysis 2
    Comparison groups
    Rivaroxaban 2.5 mg Twice Daily (BID)/15 mg Once Daily(QD) v Vitamin K antagonist (VKA)
    Number of subjects included in analysis
    1399
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.574
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.44
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.4
         upper limit
    		 5.09

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    t7g6f8Up to 12 months
    Adverse event reporting additional description
    The Safety Analysis Set is defined as all randomized subjects who received at least 1 dose of study drug.
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    18.1
    Reporting groups
    Reporting group title
    Rivaroxaban 15 mg
    Reporting group description
    		 Subjects received rivaroxaban 15 mg or 10 mg (for subjects with moderate renal impairment [creatinine clearance (CrCl): 30 to less than (<) 50 milliliter per minute (mL/min)]) once daily plus background therapy with clopidogrel 75 mg once daily or alternate P2Y12 inhibitor (prasugrel 10 mg per day or ticagrelor 90 mg twice daily) for 12 months.

    Reporting group title
    Rivaroxaban 2.5 mg BID/15 mg
    Reporting group description
    		 Subjects received rivaroxaban 2.5 mg twice daily plus background dual antiplatelet therapy (DAPT) with low dose acetylsalicylic acid (ASA) 75 to 100 mg per day and clopidogrel 75 mg once daily (or alternate P2Y12 inhibitor [prasugrel or ticagrelor]) for an intended DAPT duration of 1, 6, or 12 months. Only subjects with an intended DAPT duration of 1 or 6 month transitioned to receive rivaroxaban 15 mg or 10 mg (for subjects with moderate renal impairment) once daily plus background single antiplatelet therapy with low dose ASA for the rest of the period up to Month 12.

    Reporting group title
    vitamin K antagonist (VKA)
    Reporting group description
    		 Subjects received dose adjusted (to a target of international normalized ratio [INR] 2.0 to 3.0 [or target INR 2.0 to 2.5]) vitamin K antagonist (VKA) [eg, warfarin, acenocoumarol; assigned by the investigator according to approved formulations) once daily plus background DAPT (clopidogrel 75 mg [or alternate P2Y12 inhibitor (prasugrel or ticagrelor)] plus low dose ASA [75 to 100 mg] daily) for an intended DAPT duration of 1, 6, or 12 months. Only subjects with an intended DAPT duration of 1 or 6 month transitioned to receive dose adjusted VKA plus background single antiplatelet therapy with low dose ASA for the rest of the period up to Month 12.

    Serious adverse events
    		 Rivaroxaban 15 mg Rivaroxaban 2.5 mg BID/15 mg vitamin K antagonist (VKA)
    Total subjects affected by serious adverse events
         subjects affected / exposed
    237 / 696 (34.05%)
    225 / 706 (31.87%)
    271 / 697 (38.88%)
         number of deaths (all causes)
    19
    21
    18
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Adrenal Neoplasm
         subjects affected / exposed
    0 / 696 (0.00%)
    1 / 706 (0.14%)
    0 / 697 (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
    Ameloblastoma
         subjects affected / exposed
    1 / 696 (0.14%)
    0 / 706 (0.00%)
    0 / 697 (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 Cell Carcinoma
         subjects affected / exposed
    0 / 696 (0.00%)
    0 / 706 (0.00%)
    1 / 697 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bladder Cancer
         subjects affected / exposed
    1 / 696 (0.14%)
    1 / 706 (0.14%)
    0 / 697 (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
    Bladder Cancer Recurrent
         subjects affected / exposed
    1 / 696 (0.14%)
    0 / 706 (0.00%)
    0 / 697 (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
    0 / 696 (0.00%)
    1 / 706 (0.14%)
    0 / 697 (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
    Bowen's Disease
         subjects affected / exposed
    1 / 696 (0.14%)
    1 / 706 (0.14%)
    0 / 697 (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
    Brain Neoplasm Malignant
         subjects affected / exposed
    1 / 696 (0.14%)
    0 / 706 (0.00%)
    0 / 697 (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
    0 / 696 (0.00%)
    1 / 706 (0.14%)
    0 / 697 (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
    Breast Cancer Stage I
         subjects affected / exposed
    0 / 696 (0.00%)
    1 / 706 (0.14%)
    0 / 697 (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
    Bronchial Carcinoma
         subjects affected / exposed
    1 / 696 (0.14%)
    0 / 706 (0.00%)
    0 / 697 (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
    Cholangiocarcinoma
         subjects affected / exposed
    0 / 696 (0.00%)
    1 / 706 (0.14%)
    0 / 697 (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 Cancer
         subjects affected / exposed
    1 / 696 (0.14%)
    0 / 706 (0.00%)
    0 / 697 (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
    Colon Neoplasm
         subjects affected / exposed
    0 / 696 (0.00%)
    0 / 706 (0.00%)
    1 / 697 (0.14%)
         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
    1 / 696 (0.14%)
    0 / 706 (0.00%)
    0 / 697 (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
    Diffuse Large B-Cell Lymphoma
         subjects affected / exposed
    0 / 696 (0.00%)
    1 / 706 (0.14%)
    0 / 697 (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 Cancer Metastatic
         subjects affected / exposed
    1 / 696 (0.14%)
    0 / 706 (0.00%)
    0 / 697 (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
    Gastrointestinal Stromal Tumour
         subjects affected / exposed
    1 / 696 (0.14%)
    0 / 706 (0.00%)
    0 / 697 (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
    Hepatocellular Carcinoma
         subjects affected / exposed
    0 / 696 (0.00%)
    1 / 706 (0.14%)
    0 / 697 (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
    1 / 696 (0.14%)
    2 / 706 (0.28%)
    0 / 697 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Meningioma
         subjects affected / exposed
    0 / 696 (0.00%)
    1 / 706 (0.14%)
    0 / 697 (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
    Metastases to Liver
         subjects affected / exposed
    1 / 696 (0.14%)
    0 / 706 (0.00%)
    0 / 697 (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
    Neoplasm
         subjects affected / exposed
    0 / 696 (0.00%)
    0 / 706 (0.00%)
    1 / 697 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ovarian Cancer
         subjects affected / exposed
    1 / 696 (0.14%)
    0 / 706 (0.00%)
    0 / 697 (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
    Pituitary Tumour Benign
         subjects affected / exposed
    1 / 696 (0.14%)
    0 / 706 (0.00%)
    0 / 697 (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
    Prostate Cancer
         subjects affected / exposed
    1 / 696 (0.14%)
    0 / 706 (0.00%)
    1 / 697 (0.14%)
         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 Cancer
         subjects affected / exposed
    2 / 696 (0.29%)
    0 / 706 (0.00%)
    0 / 697 (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
    Rectal Neoplasm
         subjects affected / exposed
    0 / 696 (0.00%)
    1 / 706 (0.14%)
    0 / 697 (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 Cell Carcinoma
         subjects affected / exposed
    1 / 696 (0.14%)
    0 / 706 (0.00%)
    0 / 697 (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
    Renal Neoplasm
         subjects affected / exposed
    1 / 696 (0.14%)
    0 / 706 (0.00%)
    0 / 697 (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 Cell Lung Cancer Metastatic
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 696 (0.00%)
    1 / 706 (0.14%)
    0 / 697 (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
    Squamous Cell Carcinoma
         subjects affected / exposed
    0 / 696 (0.00%)
    1 / 706 (0.14%)
    0 / 697 (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 disorders
    Aortic Aneurysm
         subjects affected / exposed
    0 / 696 (0.00%)
    0 / 706 (0.00%)
    1 / 697 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Aortic Stenosis
         subjects affected / exposed
    1 / 696 (0.14%)
    1 / 706 (0.14%)
    0 / 697 (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
    Arterial Stenosis
         subjects affected / exposed
    0 / 696 (0.00%)
    2 / 706 (0.28%)
    0 / 697 (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
    Arteriosclerosis
         subjects affected / exposed
    0 / 696 (0.00%)
    1 / 706 (0.14%)
    1 / 697 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Arteriovenous Fistula
         subjects affected / exposed
    0 / 696 (0.00%)
    0 / 706 (0.00%)
    1 / 697 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Circulatory Collapse
         subjects affected / exposed
    0 / 696 (0.00%)
    1 / 706 (0.14%)
    0 / 697 (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
    Deep Vein Thrombosis
         subjects affected / exposed
    1 / 696 (0.14%)
    0 / 706 (0.00%)
    0 / 697 (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
    Extremity Necrosis
         subjects affected / exposed
    0 / 696 (0.00%)
    1 / 706 (0.14%)
    0 / 697 (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
    Femoral Artery Occlusion
         subjects affected / exposed
    0 / 696 (0.00%)
    0 / 706 (0.00%)
    2 / 697 (0.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haematoma
         subjects affected / exposed
    2 / 696 (0.29%)
    0 / 706 (0.00%)
    3 / 697 (0.43%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
    3 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haemorrhage
         subjects affected / exposed
    0 / 696 (0.00%)
    1 / 706 (0.14%)
    1 / 697 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypertension
         subjects affected / exposed
    3 / 696 (0.43%)
    2 / 706 (0.28%)
    2 / 697 (0.29%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypertensive Crisis
         subjects affected / exposed
    1 / 696 (0.14%)
    3 / 706 (0.42%)
    2 / 697 (0.29%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 4
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypotension
         subjects affected / exposed
    0 / 696 (0.00%)
    1 / 706 (0.14%)
    0 / 697 (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
    Intermittent Claudication
         subjects affected / exposed
    1 / 696 (0.14%)
    2 / 706 (0.28%)
    0 / 697 (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
    Lymphocele
         subjects affected / exposed
    1 / 696 (0.14%)
    0 / 706 (0.00%)
    0 / 697 (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 Hypertension
         subjects affected / exposed
    0 / 696 (0.00%)
    1 / 706 (0.14%)
    0 / 697 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Peripheral Arterial Occlusive Disease
         subjects affected / exposed
    4 / 696 (0.57%)
    0 / 706 (0.00%)
    2 / 697 (0.29%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Peripheral Artery Thrombosis
         subjects affected / exposed
    2 / 696 (0.29%)
    0 / 706 (0.00%)
    0 / 697 (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
    Peripheral Embolism
         subjects affected / exposed
    0 / 696 (0.00%)
    1 / 706 (0.14%)
    0 / 697 (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
    Peripheral Ischaemia
         subjects affected / exposed
    0 / 696 (0.00%)
    2 / 706 (0.28%)
    1 / 697 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Peripheral Vascular Disorder
         subjects affected / exposed
    0 / 696 (0.00%)
    0 / 706 (0.00%)
    1 / 697 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Shock Haemorrhagic
         subjects affected / exposed
    0 / 696 (0.00%)
    0 / 706 (0.00%)
    1 / 697 (0.14%)
         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 Occlusion
         subjects affected / exposed
    1 / 696 (0.14%)
    0 / 706 (0.00%)
    0 / 697 (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
    Venous Thrombosis
         subjects affected / exposed
    0 / 696 (0.00%)
    1 / 706 (0.14%)
    0 / 697 (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
    Surgical and medical procedures
    Angioplasty
         subjects affected / exposed
    0 / 696 (0.00%)
    1 / 706 (0.14%)
    0 / 697 (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 Replacement
         subjects affected / exposed
    0 / 696 (0.00%)
    0 / 706 (0.00%)
    1 / 697 (0.14%)
         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 Ablation
         subjects affected / exposed
    2 / 696 (0.29%)
    0 / 706 (0.00%)
    0 / 697 (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
    Cardiac Pacemaker Insertion
         subjects affected / exposed
    0 / 696 (0.00%)
    1 / 706 (0.14%)
    0 / 697 (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 Resynchronisation Therapy
         subjects affected / exposed
    0 / 696 (0.00%)
    1 / 706 (0.14%)
    0 / 697 (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
    Cardioversion
         subjects affected / exposed
    0 / 696 (0.00%)
    2 / 706 (0.28%)
    0 / 697 (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
    Cholecystectomy
         subjects affected / exposed
    2 / 696 (0.29%)
    0 / 706 (0.00%)
    0 / 697 (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
    Coronary Arterial Stent Insertion
         subjects affected / exposed
    0 / 696 (0.00%)
    0 / 706 (0.00%)
    1 / 697 (0.14%)
         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 Bypass
         subjects affected / exposed
    1 / 696 (0.14%)
    0 / 706 (0.00%)
    0 / 697 (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
    Hospitalisation
         subjects affected / exposed
    1 / 696 (0.14%)
    0 / 706 (0.00%)
    0 / 697 (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
    Ileostomy Closure
         subjects affected / exposed
    1 / 696 (0.14%)
    0 / 706 (0.00%)
    0 / 697 (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
    Implantable Defibrillator Insertion
         subjects affected / exposed
    1 / 696 (0.14%)
    2 / 706 (0.28%)
    1 / 697 (0.14%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Knee Arthroplasty
         subjects affected / exposed
    1 / 696 (0.14%)
    2 / 706 (0.28%)
    0 / 697 (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
    Mitral Valve Repair
         subjects affected / exposed
    0 / 696 (0.00%)
    1 / 706 (0.14%)
    0 / 697 (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
    Percutaneous Coronary Intervention
         subjects affected / exposed
    0 / 696 (0.00%)
    1 / 706 (0.14%)
    0 / 697 (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 Sympathetic Nerve Ablation
         subjects affected / exposed
    1 / 696 (0.14%)
    0 / 706 (0.00%)
    0 / 697 (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
    Tooth Extraction
         subjects affected / exposed
    1 / 696 (0.14%)
    0 / 706 (0.00%)
    0 / 697 (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 disorders and administration site conditions
    Catheter Site Swelling
         subjects affected / exposed
    1 / 696 (0.14%)
    0 / 706 (0.00%)
    0 / 697 (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
    Chest Discomfort
         subjects affected / exposed
    0 / 696 (0.00%)
    0 / 706 (0.00%)
    1 / 697 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Chest Pain
         subjects affected / exposed
    8 / 696 (1.15%)
    4 / 706 (0.57%)
    9 / 697 (1.29%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 4
    0 / 10
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Death
         subjects affected / exposed
    2 / 696 (0.29%)
    2 / 706 (0.28%)
    0 / 697 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 2
    0 / 2
    0 / 0
    Device Failure
         subjects affected / exposed
    1 / 696 (0.14%)
    0 / 706 (0.00%)
    0 / 697 (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 Intolerance
         subjects affected / exposed
    1 / 696 (0.14%)
    0 / 706 (0.00%)
    0 / 697 (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 Resistance
         subjects affected / exposed
    1 / 696 (0.14%)
    0 / 706 (0.00%)
    0 / 697 (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 Withdrawal Syndrome
         subjects affected / exposed
    0 / 696 (0.00%)
    0 / 706 (0.00%)
    1 / 697 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Fatigue
         subjects affected / exposed
    0 / 696 (0.00%)
    0 / 706 (0.00%)
    1 / 697 (0.14%)
         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
    0 / 696 (0.00%)
    0 / 706 (0.00%)
    1 / 697 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Malaise
         subjects affected / exposed
    0 / 696 (0.00%)
    0 / 706 (0.00%)
    1 / 697 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Medical Device Complication
         subjects affected / exposed
    1 / 696 (0.14%)
    0 / 706 (0.00%)
    0 / 697 (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
    Multi-Organ Failure
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 696 (0.00%)
    0 / 706 (0.00%)
    1 / 697 (0.14%)
         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-Cardiac Chest Pain
         subjects affected / exposed
    0 / 696 (0.00%)
    1 / 706 (0.14%)
    3 / 697 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Oedema Peripheral
         subjects affected / exposed
    2 / 696 (0.29%)
    0 / 706 (0.00%)
    0 / 697 (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
    Pyrexia
         subjects affected / exposed
    0 / 696 (0.00%)
    1 / 706 (0.14%)
    0 / 697 (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
    Sudden Cardiac Death
         subjects affected / exposed
    1 / 696 (0.14%)
    1 / 706 (0.14%)
    0 / 697 (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
    Sudden Death
         subjects affected / exposed
    2 / 696 (0.29%)
    1 / 706 (0.14%)
    3 / 697 (0.43%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 2
    0 / 1
    0 / 3
    Ulcer Haemorrhage
         subjects affected / exposed
    0 / 696 (0.00%)
    0 / 706 (0.00%)
    1 / 697 (0.14%)
         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 / 696 (0.00%)
    0 / 706 (0.00%)
    1 / 697 (0.14%)
         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
    0 / 696 (0.00%)
    1 / 706 (0.14%)
    1 / 697 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vascular Stent Thrombosis
         subjects affected / exposed
    1 / 696 (0.14%)
    2 / 706 (0.28%)
    0 / 697 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    Vessel Puncture Site Haematoma
         subjects affected / exposed
    1 / 696 (0.14%)
    0 / 706 (0.00%)
    0 / 697 (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
    Immune system disorders
    Anaphylactic Shock
         subjects affected / exposed
    1 / 696 (0.14%)
    0 / 706 (0.00%)
    0 / 697 (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
    Reproductive system and breast disorders
    Cervical Polyp
         subjects affected / exposed
    1 / 696 (0.14%)
    0 / 706 (0.00%)
    0 / 697 (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
    2 / 696 (0.29%)
    1 / 706 (0.14%)
    1 / 697 (0.14%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Acute Respiratory Failure
         subjects affected / exposed
    1 / 696 (0.14%)
    1 / 706 (0.14%)
    0 / 697 (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
    Bronchitis Chronic
         subjects affected / exposed
    1 / 696 (0.14%)
    0 / 706 (0.00%)
    0 / 697 (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
    Bronchopneumopathy
         subjects affected / exposed
    0 / 696 (0.00%)
    1 / 706 (0.14%)
    0 / 697 (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
    Chronic Obstructive Pulmonary Disease
         subjects affected / exposed
    2 / 696 (0.29%)
    2 / 706 (0.28%)
    3 / 697 (0.43%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Dyspnoea
         subjects affected / exposed
    6 / 696 (0.86%)
    6 / 706 (0.85%)
    10 / 697 (1.43%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 7
    0 / 13
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dyspnoea Exertional
         subjects affected / exposed
    0 / 696 (0.00%)
    1 / 706 (0.14%)
    3 / 697 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dyspnoea at Rest
         subjects affected / exposed
    0 / 696 (0.00%)
    1 / 706 (0.14%)
    0 / 697 (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
    Epistaxis
         subjects affected / exposed
    5 / 696 (0.72%)
    5 / 706 (0.71%)
    5 / 697 (0.72%)
         occurrences causally related to treatment / all
    6 / 6
    5 / 5
    5 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haemoptysis
         subjects affected / exposed
    2 / 696 (0.29%)
    2 / 706 (0.28%)
    4 / 697 (0.57%)
         occurrences causally related to treatment / all
    2 / 3
    2 / 2
    3 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haemothorax
         subjects affected / exposed
    0 / 696 (0.00%)
    0 / 706 (0.00%)
    1 / 697 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Interstitial Lung Disease
         subjects affected / exposed
    0 / 696 (0.00%)
    1 / 706 (0.14%)
    0 / 697 (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
    Lung Disorder
         subjects affected / exposed
    0 / 696 (0.00%)
    1 / 706 (0.14%)
    0 / 697 (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
    0 / 696 (0.00%)
    1 / 706 (0.14%)
    1 / 697 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pleurisy
         subjects affected / exposed
    1 / 696 (0.14%)
    0 / 706 (0.00%)
    0 / 697 (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
    Pulmonary Congestion
         subjects affected / exposed
    0 / 696 (0.00%)
    1 / 706 (0.14%)
    0 / 697 (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 Hypertension
         subjects affected / exposed
    0 / 696 (0.00%)
    2 / 706 (0.28%)
    0 / 697 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pulmonary Mass
         subjects affected / exposed
    0 / 696 (0.00%)
    1 / 706 (0.14%)
    1 / 697 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pulmonary Oedema
         subjects affected / exposed
    2 / 696 (0.29%)
    1 / 706 (0.14%)
    2 / 697 (0.29%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory Distress
         subjects affected / exposed
    1 / 696 (0.14%)
    0 / 706 (0.00%)
    0 / 697 (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 Failure
         subjects affected / exposed
    0 / 696 (0.00%)
    0 / 706 (0.00%)
    1 / 697 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Sleep Apnoea Syndrome
         subjects affected / exposed
    0 / 696 (0.00%)
    2 / 706 (0.28%)
    1 / 697 (0.14%)
         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
    Anxiety
         subjects affected / exposed
    0 / 696 (0.00%)
    0 / 706 (0.00%)
    1 / 697 (0.14%)
         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 Disorder
         subjects affected / exposed
    0 / 696 (0.00%)
    1 / 706 (0.14%)
    0 / 697 (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
    1 / 696 (0.14%)
    0 / 706 (0.00%)
    0 / 697 (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
    Delirium
         subjects affected / exposed
    1 / 696 (0.14%)
    0 / 706 (0.00%)
    0 / 697 (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
    Depression
         subjects affected / exposed
    0 / 696 (0.00%)
    0 / 706 (0.00%)
    1 / 697 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hallucination
         subjects affected / exposed
    1 / 696 (0.14%)
    0 / 706 (0.00%)
    0 / 697 (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
    Investigations
    Biopsy Prostate
         subjects affected / exposed
    0 / 696 (0.00%)
    0 / 706 (0.00%)
    1 / 697 (0.14%)
         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 Stress Test
         subjects affected / exposed
    0 / 696 (0.00%)
    1 / 706 (0.14%)
    0 / 697 (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
    Ejection Fraction Decreased
         subjects affected / exposed
    0 / 696 (0.00%)
    1 / 706 (0.14%)
    0 / 697 (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
    Electrocardiogram Ambulatory Abnormal
         subjects affected / exposed
    0 / 696 (0.00%)
    0 / 706 (0.00%)
    1 / 697 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haemoglobin Decreased
         subjects affected / exposed
    0 / 696 (0.00%)
    0 / 706 (0.00%)
    1 / 697 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatic Enzyme Increased
         subjects affected / exposed
    0 / 696 (0.00%)
    2 / 706 (0.28%)
    0 / 697 (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
    International Normalised Ratio Increased
         subjects affected / exposed
    0 / 696 (0.00%)
    0 / 706 (0.00%)
    4 / 697 (0.57%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    4 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lipids Increased
         subjects affected / exposed
    0 / 696 (0.00%)
    0 / 706 (0.00%)
    1 / 697 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Compression Fracture
         subjects affected / exposed
    0 / 696 (0.00%)
    0 / 706 (0.00%)
    1 / 697 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Concussion
         subjects affected / exposed
    0 / 696 (0.00%)
    0 / 706 (0.00%)
    1 / 697 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Contusion
         subjects affected / exposed
    0 / 696 (0.00%)
    0 / 706 (0.00%)
    1 / 697 (0.14%)
         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 Restenosis
         subjects affected / exposed
    0 / 696 (0.00%)
    1 / 706 (0.14%)
    0 / 697 (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
    Craniocerebral Injury
         subjects affected / exposed
    0 / 696 (0.00%)
    0 / 706 (0.00%)
    1 / 697 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Fall
         subjects affected / exposed
    1 / 696 (0.14%)
    2 / 706 (0.28%)
    1 / 697 (0.14%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Femoral Neck Fracture
         subjects affected / exposed
    2 / 696 (0.29%)
    0 / 706 (0.00%)
    0 / 697 (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
    Hip Fracture
         subjects affected / exposed
    0 / 696 (0.00%)
    1 / 706 (0.14%)
    0 / 697 (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
    Humerus Fracture
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 696 (0.00%)
    0 / 706 (0.00%)
    2 / 697 (0.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Incisional Hernia
         subjects affected / exposed
    1 / 696 (0.14%)
    0 / 706 (0.00%)
    0 / 697 (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 Limb Fracture
         subjects affected / exposed
    0 / 696 (0.00%)
    1 / 706 (0.14%)
    0 / 697 (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
    Muscle Rupture
         subjects affected / exposed
    0 / 696 (0.00%)
    1 / 706 (0.14%)
    0 / 697 (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
    5 / 696 (0.72%)
    6 / 706 (0.85%)
    7 / 697 (1.00%)
         occurrences causally related to treatment / all
    1 / 5
    5 / 6
    7 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumothorax Traumatic
         subjects affected / exposed
    0 / 696 (0.00%)
    1 / 706 (0.14%)
    0 / 697 (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 Procedural Complication
         subjects affected / exposed
    1 / 696 (0.14%)
    0 / 706 (0.00%)
    0 / 697 (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 Haematoma
         subjects affected / exposed
    0 / 696 (0.00%)
    0 / 706 (0.00%)
    2 / 697 (0.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Post Procedural Haemorrhage
         subjects affected / exposed
    1 / 696 (0.14%)
    1 / 706 (0.14%)
    0 / 697 (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
    Pubis Fracture
         subjects affected / exposed
    1 / 696 (0.14%)
    0 / 706 (0.00%)
    0 / 697 (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
    Radius Fracture
         subjects affected / exposed
    1 / 696 (0.14%)
    0 / 706 (0.00%)
    0 / 697 (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 / 696 (0.14%)
    0 / 706 (0.00%)
    1 / 697 (0.14%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Road Traffic Accident
         subjects affected / exposed
    0 / 696 (0.00%)
    1 / 706 (0.14%)
    0 / 697 (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
    Subdural Haematoma
         subjects affected / exposed
    1 / 696 (0.14%)
    0 / 706 (0.00%)
    2 / 697 (0.29%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    Subdural Haemorrhage
         subjects affected / exposed
    0 / 696 (0.00%)
    0 / 706 (0.00%)
    1 / 697 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Toxicity to Various Agents
         subjects affected / exposed
    0 / 696 (0.00%)
    1 / 706 (0.14%)
    0 / 697 (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
    Traumatic Fracture
         subjects affected / exposed
    1 / 696 (0.14%)
    0 / 706 (0.00%)
    1 / 697 (0.14%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Traumatic Haematoma
         subjects affected / exposed
    0 / 696 (0.00%)
    0 / 706 (0.00%)
    1 / 697 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Upper Limb Fracture
         subjects affected / exposed
    0 / 696 (0.00%)
    0 / 706 (0.00%)
    1 / 697 (0.14%)
         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 Pseudoaneurysm
         subjects affected / exposed
    0 / 696 (0.00%)
    1 / 706 (0.14%)
    1 / 697 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Wound Dehiscence
         subjects affected / exposed
    0 / 696 (0.00%)
    1 / 706 (0.14%)
    0 / 697 (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 disorders
    Acute Coronary Syndrome
         subjects affected / exposed
    3 / 696 (0.43%)
    1 / 706 (0.14%)
    1 / 697 (0.14%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Acute Myocardial Infarction
         subjects affected / exposed
    5 / 696 (0.72%)
    5 / 706 (0.71%)
    3 / 697 (0.43%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 5
    0 / 3
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Angina Pectoris
         subjects affected / exposed
    7 / 696 (1.01%)
    13 / 706 (1.84%)
    15 / 697 (2.15%)
         occurrences causally related to treatment / all
    0 / 9
    0 / 16
    0 / 16
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Angina Unstable
         subjects affected / exposed
    16 / 696 (2.30%)
    12 / 706 (1.70%)
    23 / 697 (3.30%)
         occurrences causally related to treatment / all
    1 / 17
    0 / 13
    0 / 24
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Atrial Fibrillation
         subjects affected / exposed
    13 / 696 (1.87%)
    21 / 706 (2.97%)
    23 / 697 (3.30%)
         occurrences causally related to treatment / all
    0 / 17
    0 / 24
    0 / 30
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Atrial Flutter
         subjects affected / exposed
    0 / 696 (0.00%)
    5 / 706 (0.71%)
    4 / 697 (0.57%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 5
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Atrial Tachycardia
         subjects affected / exposed
    0 / 696 (0.00%)
    2 / 706 (0.28%)
    1 / 697 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Atrial Thrombosis
         subjects affected / exposed
    4 / 696 (0.57%)
    1 / 706 (0.14%)
    0 / 697 (0.00%)
         occurrences causally related to treatment / all
    2 / 4
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Atrioventricular Block
         subjects affected / exposed
    2 / 696 (0.29%)
    0 / 706 (0.00%)
    1 / 697 (0.14%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Atrioventricular Block Complete
         subjects affected / exposed
    1 / 696 (0.14%)
    1 / 706 (0.14%)
    0 / 697 (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
    Bradyarrhythmia
         subjects affected / exposed
    0 / 696 (0.00%)
    1 / 706 (0.14%)
    0 / 697 (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
    2 / 696 (0.29%)
    1 / 706 (0.14%)
    2 / 697 (0.29%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac Arrest
         subjects affected / exposed
    0 / 696 (0.00%)
    2 / 706 (0.28%)
    2 / 697 (0.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Cardiac Disorder
         subjects affected / exposed
    0 / 696 (0.00%)
    0 / 706 (0.00%)
    1 / 697 (0.14%)
         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 Failure
    alternative assessment type: Systematic
         subjects affected / exposed
    21 / 696 (3.02%)
    16 / 706 (2.27%)
    31 / 697 (4.45%)
         occurrences causally related to treatment / all
    0 / 25
    0 / 21
    0 / 32
         deaths causally related to treatment / all
    0 / 2
    0 / 2
    0 / 1
    Cardiac Failure Acute
    alternative assessment type: Systematic
         subjects affected / exposed
    3 / 696 (0.43%)
    3 / 706 (0.42%)
    4 / 697 (0.57%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
    0 / 4
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Cardiac Failure Chronic
         subjects affected / exposed
    3 / 696 (0.43%)
    1 / 706 (0.14%)
    3 / 697 (0.43%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Cardiac Failure Congestive
    alternative assessment type: Systematic
         subjects affected / exposed
    7 / 696 (1.01%)
    4 / 706 (0.57%)
    11 / 697 (1.58%)
         occurrences causally related to treatment / all
    0 / 9
    0 / 5
    1 / 11
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    Cardiac Pseudoaneurysm
         subjects affected / exposed
    0 / 696 (0.00%)
    1 / 706 (0.14%)
    0 / 697 (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
    Cardiogenic Shock
         subjects affected / exposed
    0 / 696 (0.00%)
    1 / 706 (0.14%)
    1 / 697 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Cardiomyopathy
         subjects affected / exposed
    1 / 696 (0.14%)
    0 / 706 (0.00%)
    1 / 697 (0.14%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiovascular Disorder
         subjects affected / exposed
    2 / 696 (0.29%)
    0 / 706 (0.00%)
    0 / 697 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Coronary Artery Disease
         subjects affected / exposed
    3 / 696 (0.43%)
    5 / 706 (0.71%)
    2 / 697 (0.29%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 7
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Coronary Artery Stenosis
         subjects affected / exposed
    0 / 696 (0.00%)
    1 / 706 (0.14%)
    1 / 697 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Coronary Artery Thrombosis
         subjects affected / exposed
    0 / 696 (0.00%)
    1 / 706 (0.14%)
    0 / 697 (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
    Dressler's Syndrome
         subjects affected / exposed
    0 / 696 (0.00%)
    0 / 706 (0.00%)
    1 / 697 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ischaemic Cardiomyopathy
         subjects affected / exposed
    1 / 696 (0.14%)
    0 / 706 (0.00%)
    0 / 697 (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
    Left Ventricular Dysfunction
         subjects affected / exposed
    1 / 696 (0.14%)
    0 / 706 (0.00%)
    1 / 697 (0.14%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Left Ventricular Failure
         subjects affected / exposed
    1 / 696 (0.14%)
    1 / 706 (0.14%)
    0 / 697 (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
    Myocardial Infarction
         subjects affected / exposed
    0 / 696 (0.00%)
    1 / 706 (0.14%)
    2 / 697 (0.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Myocardial Ischaemia
         subjects affected / exposed
    0 / 696 (0.00%)
    1 / 706 (0.14%)
    2 / 697 (0.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Palpitations
         subjects affected / exposed
    0 / 696 (0.00%)
    1 / 706 (0.14%)
    2 / 697 (0.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pericardial Effusion
         subjects affected / exposed
    0 / 696 (0.00%)
    0 / 706 (0.00%)
    2 / 697 (0.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pericardial Haemorrhage
         subjects affected / exposed
    1 / 696 (0.14%)
    0 / 706 (0.00%)
    0 / 697 (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 / 696 (0.00%)
    0 / 706 (0.00%)
    1 / 697 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Sinus Bradycardia
         subjects affected / exposed
    0 / 696 (0.00%)
    0 / 706 (0.00%)
    1 / 697 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Sinus Node Dysfunction
         subjects affected / exposed
    4 / 696 (0.57%)
    1 / 706 (0.14%)
    2 / 697 (0.29%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Supraventricular Tachycardia
         subjects affected / exposed
    0 / 696 (0.00%)
    2 / 706 (0.28%)
    1 / 697 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Tachyarrhythmia
         subjects affected / exposed
    0 / 696 (0.00%)
    0 / 706 (0.00%)
    1 / 697 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Tachycardia Induced Cardiomyopathy
         subjects affected / exposed
    1 / 696 (0.14%)
    0 / 706 (0.00%)
    0 / 697 (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
    Ventricular Arrhythmia
         subjects affected / exposed
    0 / 696 (0.00%)
    0 / 706 (0.00%)
    1 / 697 (0.14%)
         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 Extrasystoles
         subjects affected / exposed
    1 / 696 (0.14%)
    0 / 706 (0.00%)
    0 / 697 (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
    Ventricular Fibrillation
         subjects affected / exposed
    2 / 696 (0.29%)
    1 / 706 (0.14%)
    1 / 697 (0.14%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ventricular Tachycardia
         subjects affected / exposed
    3 / 696 (0.43%)
    0 / 706 (0.00%)
    1 / 697 (0.14%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Aphasia
         subjects affected / exposed
    1 / 696 (0.14%)
    0 / 706 (0.00%)
    0 / 697 (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
    Carotid Artery Stenosis
         subjects affected / exposed
    0 / 696 (0.00%)
    0 / 706 (0.00%)
    1 / 697 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cerebral Haemorrhage
         subjects affected / exposed
    0 / 696 (0.00%)
    2 / 706 (0.28%)
    4 / 697 (0.57%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 4
    8 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    3 / 3
    Cerebral Infarction
         subjects affected / exposed
    1 / 696 (0.14%)
    1 / 706 (0.14%)
    0 / 697 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cerebral Ischaemia
         subjects affected / exposed
    0 / 696 (0.00%)
    0 / 706 (0.00%)
    1 / 697 (0.14%)
         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
    2 / 696 (0.29%)
    4 / 706 (0.57%)
    0 / 697 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Dizziness
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 696 (0.14%)
    1 / 706 (0.14%)
    0 / 697 (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
    Dizziness Postural
         subjects affected / exposed
    0 / 696 (0.00%)
    0 / 706 (0.00%)
    1 / 697 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Encephalopathy
         subjects affected / exposed
    0 / 696 (0.00%)
    1 / 706 (0.14%)
    0 / 697 (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
    Epilepsy
         subjects affected / exposed
    0 / 696 (0.00%)
    0 / 706 (0.00%)
    1 / 697 (0.14%)
         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 Stroke
         subjects affected / exposed
    1 / 696 (0.14%)
    0 / 706 (0.00%)
    1 / 697 (0.14%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
    Hemianopia
         subjects affected / exposed
    1 / 696 (0.14%)
    0 / 706 (0.00%)
    0 / 697 (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
    Hemiparesis
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 696 (0.00%)
    0 / 706 (0.00%)
    1 / 697 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypoaesthesia
         subjects affected / exposed
    0 / 696 (0.00%)
    0 / 706 (0.00%)
    1 / 697 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Intercostal Neuralgia
         subjects affected / exposed
    0 / 696 (0.00%)
    1 / 706 (0.14%)
    0 / 697 (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
    Intracranial Haematoma
         subjects affected / exposed
    1 / 696 (0.14%)
    0 / 706 (0.00%)
    0 / 697 (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
    Ischaemic Stroke
         subjects affected / exposed
    5 / 696 (0.72%)
    2 / 706 (0.28%)
    4 / 697 (0.57%)
         occurrences causally related to treatment / all
    1 / 6
    1 / 2
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Lacunar Infarction
         subjects affected / exposed
    1 / 696 (0.14%)
    1 / 706 (0.14%)
    0 / 697 (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
    Neuralgia
         subjects affected / exposed
    0 / 696 (0.00%)
    1 / 706 (0.14%)
    0 / 697 (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
    Parkinson's Disease
         subjects affected / exposed
    1 / 696 (0.14%)
    0 / 706 (0.00%)
    0 / 697 (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
    Presyncope
         subjects affected / exposed
    1 / 696 (0.14%)
    0 / 706 (0.00%)
    0 / 697 (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
    Sciatica
         subjects affected / exposed
    1 / 696 (0.14%)
    0 / 706 (0.00%)
    0 / 697 (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
    Syncope
         subjects affected / exposed
    1 / 696 (0.14%)
    4 / 706 (0.57%)
    8 / 697 (1.15%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 5
    0 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Tension Headache
         subjects affected / exposed
    1 / 696 (0.14%)
    0 / 706 (0.00%)
    0 / 697 (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
    1 / 696 (0.14%)
    1 / 706 (0.14%)
    3 / 697 (0.43%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Viith Nerve Paralysis
         subjects affected / exposed
    0 / 696 (0.00%)
    0 / 706 (0.00%)
    1 / 697 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    5 / 696 (0.72%)
    4 / 706 (0.57%)
    4 / 697 (0.57%)
         occurrences causally related to treatment / all
    4 / 5
    2 / 4
    3 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haemorrhagic Anaemia
         subjects affected / exposed
    0 / 696 (0.00%)
    0 / 706 (0.00%)
    1 / 697 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypergammaglobulinaemia
         subjects affected / exposed
    1 / 696 (0.14%)
    0 / 706 (0.00%)
    0 / 697 (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
    Hypochromic Anaemia
         subjects affected / exposed
    0 / 696 (0.00%)
    1 / 706 (0.14%)
    0 / 697 (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
    Microcytic Anaemia
         subjects affected / exposed
    0 / 696 (0.00%)
    1 / 706 (0.14%)
    1 / 697 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    Deafness Neurosensory
         subjects affected / exposed
    1 / 696 (0.14%)
    0 / 706 (0.00%)
    0 / 697 (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
    Vertigo
         subjects affected / exposed
    0 / 696 (0.00%)
    1 / 706 (0.14%)
    0 / 697 (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
    Age-Related Macular Degeneration
         subjects affected / exposed
    1 / 696 (0.14%)
    0 / 706 (0.00%)
    0 / 697 (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
    0 / 696 (0.00%)
    0 / 706 (0.00%)
    3 / 697 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Eye Haemorrhage
         subjects affected / exposed
    0 / 696 (0.00%)
    1 / 706 (0.14%)
    1 / 697 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vitreous Haemorrhage
         subjects affected / exposed
    0 / 696 (0.00%)
    0 / 706 (0.00%)
    1 / 697 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal Pain
         subjects affected / exposed
    3 / 696 (0.43%)
    0 / 706 (0.00%)
    0 / 697 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Abdominal Pain Lower
         subjects affected / exposed
    0 / 696 (0.00%)
    1 / 706 (0.14%)
    0 / 697 (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
    Acute Abdomen
         subjects affected / exposed
    0 / 696 (0.00%)
    1 / 706 (0.14%)
    0 / 697 (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
    Anal Fistula
         subjects affected / exposed
    1 / 696 (0.14%)
    0 / 706 (0.00%)
    0 / 697 (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
    Anal Haemorrhage
         subjects affected / exposed
    0 / 696 (0.00%)
    0 / 706 (0.00%)
    2 / 697 (0.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Barrett's Oesophagus
         subjects affected / exposed
    0 / 696 (0.00%)
    0 / 706 (0.00%)
    1 / 697 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Change of Bowel Habit
         subjects affected / exposed
    1 / 696 (0.14%)
    0 / 706 (0.00%)
    0 / 697 (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
    Colitis Microscopic
         subjects affected / exposed
    0 / 696 (0.00%)
    1 / 706 (0.14%)
    0 / 697 (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
    Constipation
         subjects affected / exposed
    0 / 696 (0.00%)
    1 / 706 (0.14%)
    1 / 697 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Crohn's Disease
         subjects affected / exposed
    1 / 696 (0.14%)
    0 / 706 (0.00%)
    0 / 697 (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
    Diarrhoea
         subjects affected / exposed
    1 / 696 (0.14%)
    0 / 706 (0.00%)
    1 / 697 (0.14%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Duodenal Ulcer
         subjects affected / exposed
    1 / 696 (0.14%)
    0 / 706 (0.00%)
    0 / 697 (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
    Dysphagia
         subjects affected / exposed
    1 / 696 (0.14%)
    0 / 706 (0.00%)
    0 / 697 (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
    Enteritis
         subjects affected / exposed
    0 / 696 (0.00%)
    0 / 706 (0.00%)
    2 / 697 (0.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Enterocolitis
         subjects affected / exposed
    0 / 696 (0.00%)
    1 / 706 (0.14%)
    0 / 697 (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
    Faecaloma
         subjects affected / exposed
    0 / 696 (0.00%)
    1 / 706 (0.14%)
    0 / 697 (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
    Gastric Haemorrhage
         subjects affected / exposed
    0 / 696 (0.00%)
    1 / 706 (0.14%)
    1 / 697 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    Gastric Mucosa Erythema
         subjects affected / exposed
    0 / 696 (0.00%)
    1 / 706 (0.14%)
    0 / 697 (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
    Gastric Ulcer
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 696 (0.14%)
    3 / 706 (0.42%)
    3 / 697 (0.43%)
         occurrences causally related to treatment / all
    1 / 2
    2 / 3
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastric Ulcer Haemorrhage
         subjects affected / exposed
    0 / 696 (0.00%)
    0 / 706 (0.00%)
    2 / 697 (0.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Gastritis
         subjects affected / exposed
    2 / 696 (0.29%)
    1 / 706 (0.14%)
    1 / 697 (0.14%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastritis Erosive
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 696 (0.00%)
    2 / 706 (0.28%)
    2 / 697 (0.29%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastritis Haemorrhagic
         subjects affected / exposed
    1 / 696 (0.14%)
    1 / 706 (0.14%)
    1 / 697 (0.14%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastroduodenitis Haemorrhagic
         subjects affected / exposed
    0 / 696 (0.00%)
    0 / 706 (0.00%)
    1 / 697 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal Haemorrhage
    alternative assessment type: Systematic
         subjects affected / exposed
    7 / 696 (1.01%)
    7 / 706 (0.99%)
    9 / 697 (1.29%)
         occurrences causally related to treatment / all
    7 / 7
    6 / 7
    7 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal Ulcer
         subjects affected / exposed
    0 / 696 (0.00%)
    1 / 706 (0.14%)
    0 / 697 (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
    Gastrooesophageal Reflux Disease
         subjects affected / exposed
    1 / 696 (0.14%)
    0 / 706 (0.00%)
    1 / 697 (0.14%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haematemesis
         subjects affected / exposed
    1 / 696 (0.14%)
    0 / 706 (0.00%)
    0 / 697 (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
    Haematochezia
         subjects affected / exposed
    1 / 696 (0.14%)
    1 / 706 (0.14%)
    0 / 697 (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
    Haemorrhoidal Haemorrhage
         subjects affected / exposed
    0 / 696 (0.00%)
    1 / 706 (0.14%)
    0 / 697 (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
    Haemorrhoids
         subjects affected / exposed
    0 / 696 (0.00%)
    1 / 706 (0.14%)
    0 / 697 (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
    Hiatus Hernia
         subjects affected / exposed
    0 / 696 (0.00%)
    0 / 706 (0.00%)
    1 / 697 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Impaired Gastric Emptying
         subjects affected / exposed
    1 / 696 (0.14%)
    0 / 706 (0.00%)
    0 / 697 (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
    3 / 696 (0.43%)
    0 / 706 (0.00%)
    1 / 697 (0.14%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Intestinal Haemorrhage
         subjects affected / exposed
    1 / 696 (0.14%)
    0 / 706 (0.00%)
    0 / 697 (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
    Intestinal Ischaemia
         subjects affected / exposed
    0 / 696 (0.00%)
    1 / 706 (0.14%)
    1 / 697 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Intestinal Obstruction
         subjects affected / exposed
    1 / 696 (0.14%)
    1 / 706 (0.14%)
    0 / 697 (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
    Intra-Abdominal Haematoma
         subjects affected / exposed
    1 / 696 (0.14%)
    0 / 706 (0.00%)
    1 / 697 (0.14%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Lower Gastrointestinal Haemorrhage
         subjects affected / exposed
    0 / 696 (0.00%)
    1 / 706 (0.14%)
    1 / 697 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Mallory-Weiss Syndrome
         subjects affected / exposed
    1 / 696 (0.14%)
    0 / 706 (0.00%)
    0 / 697 (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
    Melaena
         subjects affected / exposed
    0 / 696 (0.00%)
    1 / 706 (0.14%)
    4 / 697 (0.57%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    3 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Mouth Haemorrhage
         subjects affected / exposed
    0 / 696 (0.00%)
    0 / 706 (0.00%)
    1 / 697 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    1 / 696 (0.14%)
    0 / 706 (0.00%)
    0 / 697 (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
    Pancreatitis
         subjects affected / exposed
    2 / 696 (0.29%)
    0 / 706 (0.00%)
    1 / 697 (0.14%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pancreatitis Chronic
         subjects affected / exposed
    1 / 696 (0.14%)
    0 / 706 (0.00%)
    0 / 697 (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
    Rectal Haemorrhage
         subjects affected / exposed
    4 / 696 (0.57%)
    2 / 706 (0.28%)
    1 / 697 (0.14%)
         occurrences causally related to treatment / all
    3 / 4
    3 / 3
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Small Intestinal Obstruction
         subjects affected / exposed
    0 / 696 (0.00%)
    0 / 706 (0.00%)
    1 / 697 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Stomatitis
         subjects affected / exposed
    1 / 696 (0.14%)
    0 / 706 (0.00%)
    0 / 697 (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
    Tongue Haemorrhage
         subjects affected / exposed
    0 / 696 (0.00%)
    0 / 706 (0.00%)
    1 / 697 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Upper Gastrointestinal Haemorrhage
         subjects affected / exposed
    2 / 696 (0.29%)
    1 / 706 (0.14%)
    2 / 697 (0.29%)
         occurrences causally related to treatment / all
    2 / 2
    1 / 1
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Bile Duct Stone
         subjects affected / exposed
    1 / 696 (0.14%)
    0 / 706 (0.00%)
    0 / 697 (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
    Cholangitis
         subjects affected / exposed
    1 / 696 (0.14%)
    0 / 706 (0.00%)
    0 / 697 (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
    Cholecystitis
         subjects affected / exposed
    0 / 696 (0.00%)
    1 / 706 (0.14%)
    2 / 697 (0.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cholecystitis Acute
         subjects affected / exposed
    1 / 696 (0.14%)
    1 / 706 (0.14%)
    1 / 697 (0.14%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cholecystitis Chronic
         subjects affected / exposed
    0 / 696 (0.00%)
    0 / 706 (0.00%)
    1 / 697 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cholelithiasis
         subjects affected / exposed
    1 / 696 (0.14%)
    0 / 706 (0.00%)
    3 / 697 (0.43%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatic Cyst
         subjects affected / exposed
    1 / 696 (0.14%)
    0 / 706 (0.00%)
    0 / 697 (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 Acute
         subjects affected / exposed
    1 / 696 (0.14%)
    0 / 706 (0.00%)
    0 / 697 (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
    Hepatitis Toxic
         subjects affected / exposed
    1 / 696 (0.14%)
    0 / 706 (0.00%)
    0 / 697 (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
    Hepatocellular Injury
         subjects affected / exposed
    0 / 696 (0.00%)
    0 / 706 (0.00%)
    1 / 697 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Jaundice
         subjects affected / exposed
    1 / 696 (0.14%)
    0 / 706 (0.00%)
    0 / 697 (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 and subcutaneous tissue disorders
    Diabetic Foot
         subjects affected / exposed
    0 / 696 (0.00%)
    0 / 706 (0.00%)
    1 / 697 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Neurodermatitis
         subjects affected / exposed
    0 / 696 (0.00%)
    0 / 706 (0.00%)
    1 / 697 (0.14%)
         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 Necrosis
         subjects affected / exposed
    0 / 696 (0.00%)
    1 / 706 (0.14%)
    0 / 697 (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
    Skin Ulcer
         subjects affected / exposed
    0 / 696 (0.00%)
    1 / 706 (0.14%)
    0 / 697 (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
    Urticaria
         subjects affected / exposed
    1 / 696 (0.14%)
    0 / 706 (0.00%)
    0 / 697 (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
    Renal and urinary disorders
    Acute Kidney Injury
    alternative assessment type: Systematic
         subjects affected / exposed
    2 / 696 (0.29%)
    2 / 706 (0.28%)
    1 / 697 (0.14%)
         occurrences causally related to treatment / all
    0 / 2
    1 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    Bladder Tamponade
         subjects affected / exposed
    0 / 696 (0.00%)
    0 / 706 (0.00%)
    1 / 697 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Calculus Ureteric
         subjects affected / exposed
    0 / 696 (0.00%)
    0 / 706 (0.00%)
    1 / 697 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Calculus Urethral
         subjects affected / exposed
    0 / 696 (0.00%)
    0 / 706 (0.00%)
    1 / 697 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Calculus Urinary
         subjects affected / exposed
    0 / 696 (0.00%)
    0 / 706 (0.00%)
    1 / 697 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haematuria
         subjects affected / exposed
    5 / 696 (0.72%)
    3 / 706 (0.42%)
    4 / 697 (0.57%)
         occurrences causally related to treatment / all
    5 / 5
    3 / 3
    4 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haemorrhage Urinary Tract
         subjects affected / exposed
    1 / 696 (0.14%)
    0 / 706 (0.00%)
    0 / 697 (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
    Hydronephrosis
         subjects affected / exposed
    1 / 696 (0.14%)
    0 / 706 (0.00%)
    1 / 697 (0.14%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Prerenal Failure
         subjects affected / exposed
    1 / 696 (0.14%)
    0 / 706 (0.00%)
    0 / 697 (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
    Renal Artery Stenosis
         subjects affected / exposed
    0 / 696 (0.00%)
    1 / 706 (0.14%)
    0 / 697 (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 Failure
         subjects affected / exposed
    2 / 696 (0.29%)
    1 / 706 (0.14%)
    0 / 697 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal Impairment
         subjects affected / exposed
    1 / 696 (0.14%)
    0 / 706 (0.00%)
    0 / 697 (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
    Urethral Haemorrhage
         subjects affected / exposed
    0 / 696 (0.00%)
    0 / 706 (0.00%)
    1 / 697 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Urethral Stenosis
         subjects affected / exposed
    0 / 696 (0.00%)
    1 / 706 (0.14%)
    0 / 697 (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 Retention
         subjects affected / exposed
    0 / 696 (0.00%)
    2 / 706 (0.28%)
    0 / 697 (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
    Endocrine disorders
    Hyperthyroidism
         subjects affected / exposed
    0 / 696 (0.00%)
    1 / 706 (0.14%)
    0 / 697 (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
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    0 / 696 (0.00%)
    2 / 706 (0.28%)
    1 / 697 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Arthritis
         subjects affected / exposed
    1 / 696 (0.14%)
    0 / 706 (0.00%)
    0 / 697 (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
    Back Pain
         subjects affected / exposed
    1 / 696 (0.14%)
    1 / 706 (0.14%)
    0 / 697 (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
    Bursitis
         subjects affected / exposed
    0 / 696 (0.00%)
    1 / 706 (0.14%)
    0 / 697 (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
    Exostosis
         subjects affected / exposed
    0 / 696 (0.00%)
    1 / 706 (0.14%)
    0 / 697 (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
    Gouty Arthritis
         subjects affected / exposed
    0 / 696 (0.00%)
    1 / 706 (0.14%)
    0 / 697 (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
    Haemarthrosis
         subjects affected / exposed
    0 / 696 (0.00%)
    0 / 706 (0.00%)
    1 / 697 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Intervertebral Disc Protrusion
         subjects affected / exposed
    0 / 696 (0.00%)
    1 / 706 (0.14%)
    0 / 697 (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
    Joint Effusion
         subjects affected / exposed
    0 / 696 (0.00%)
    0 / 706 (0.00%)
    1 / 697 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lumbar Spinal Stenosis
         subjects affected / exposed
    0 / 696 (0.00%)
    0 / 706 (0.00%)
    1 / 697 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal Disorder
         subjects affected / exposed
    1 / 696 (0.14%)
    0 / 706 (0.00%)
    0 / 697 (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
    Neck Pain
         subjects affected / exposed
    0 / 696 (0.00%)
    0 / 706 (0.00%)
    1 / 697 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Osteoarthritis
         subjects affected / exposed
    1 / 696 (0.14%)
    1 / 706 (0.14%)
    3 / 697 (0.43%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Osteochondrosis
         subjects affected / exposed
    1 / 696 (0.14%)
    0 / 706 (0.00%)
    0 / 697 (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
    Pain in Extremity
         subjects affected / exposed
    0 / 696 (0.00%)
    0 / 706 (0.00%)
    1 / 697 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Periarthritis
         subjects affected / exposed
    1 / 696 (0.14%)
    0 / 706 (0.00%)
    0 / 697 (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
    Rhabdomyolysis
         subjects affected / exposed
    0 / 696 (0.00%)
    0 / 706 (0.00%)
    1 / 697 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Rheumatic Disorder
         subjects affected / exposed
    0 / 696 (0.00%)
    0 / 706 (0.00%)
    1 / 697 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Spinal Column Stenosis
         subjects affected / exposed
    0 / 696 (0.00%)
    0 / 706 (0.00%)
    1 / 697 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Spinal Disorder
         subjects affected / exposed
    1 / 696 (0.14%)
    0 / 706 (0.00%)
    0 / 697 (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 Osteoarthritis
         subjects affected / exposed
    1 / 696 (0.14%)
    0 / 706 (0.00%)
    0 / 697 (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 Pain
         subjects affected / exposed
    0 / 696 (0.00%)
    0 / 706 (0.00%)
    1 / 697 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Abdominal Wall Abscess
         subjects affected / exposed
    2 / 696 (0.29%)
    0 / 706 (0.00%)
    0 / 697 (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
    Abscess Limb
         subjects affected / exposed
    0 / 696 (0.00%)
    0 / 706 (0.00%)
    1 / 697 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Appendicitis
         subjects affected / exposed
    1 / 696 (0.14%)
    0 / 706 (0.00%)
    1 / 697 (0.14%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Arthritis Bacterial
         subjects affected / exposed
    0 / 696 (0.00%)
    2 / 706 (0.28%)
    0 / 697 (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
    Bacterial Sepsis
         subjects affected / exposed
    0 / 696 (0.00%)
    1 / 706 (0.14%)
    0 / 697 (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
    Bronchitis
         subjects affected / exposed
    3 / 696 (0.43%)
    1 / 706 (0.14%)
    1 / 697 (0.14%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bronchitis Bacterial
         subjects affected / exposed
    1 / 696 (0.14%)
    0 / 706 (0.00%)
    0 / 697 (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 / 696 (0.14%)
    1 / 706 (0.14%)
    2 / 697 (0.29%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Clostridium Difficile Colitis
         subjects affected / exposed
    1 / 696 (0.14%)
    0 / 706 (0.00%)
    0 / 697 (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
    Cystitis
         subjects affected / exposed
    1 / 696 (0.14%)
    0 / 706 (0.00%)
    0 / 697 (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
    Diverticulitis
         subjects affected / exposed
    1 / 696 (0.14%)
    0 / 706 (0.00%)
    0 / 697 (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
    Encephalitis Viral
         subjects affected / exposed
    0 / 696 (0.00%)
    1 / 706 (0.14%)
    0 / 697 (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
    Epididymitis
         subjects affected / exposed
    0 / 696 (0.00%)
    1 / 706 (0.14%)
    0 / 697 (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
    Erysipelas
         subjects affected / exposed
    0 / 696 (0.00%)
    1 / 706 (0.14%)
    0 / 697 (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
    Gangrene
         subjects affected / exposed
    0 / 696 (0.00%)
    2 / 706 (0.28%)
    1 / 697 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    2 / 696 (0.29%)
    0 / 706 (0.00%)
    1 / 697 (0.14%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal Infection
         subjects affected / exposed
    1 / 696 (0.14%)
    0 / 706 (0.00%)
    0 / 697 (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
    Haematoma Infection
         subjects affected / exposed
    0 / 696 (0.00%)
    0 / 706 (0.00%)
    1 / 697 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Herpes Zoster
         subjects affected / exposed
    0 / 696 (0.00%)
    1 / 706 (0.14%)
    0 / 697 (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
    Infected Skin Ulcer
         subjects affected / exposed
    1 / 696 (0.14%)
    0 / 706 (0.00%)
    0 / 697 (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
    Infective Exacerbation of Chronic Obstructive Airways Disease
         subjects affected / exposed
    0 / 696 (0.00%)
    1 / 706 (0.14%)
    1 / 697 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Influenza
         subjects affected / exposed
    1 / 696 (0.14%)
    0 / 706 (0.00%)
    1 / 697 (0.14%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Intervertebral Discitis
         subjects affected / exposed
    0 / 696 (0.00%)
    1 / 706 (0.14%)
    0 / 697 (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
    Liver Abscess
         subjects affected / exposed
    1 / 696 (0.14%)
    0 / 706 (0.00%)
    0 / 697 (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
    Localised Infection
         subjects affected / exposed
    0 / 696 (0.00%)
    1 / 706 (0.14%)
    0 / 697 (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
    Lower Respiratory Tract Infection
         subjects affected / exposed
    1 / 696 (0.14%)
    0 / 706 (0.00%)
    0 / 697 (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
    Nasopharyngitis
         subjects affected / exposed
    0 / 696 (0.00%)
    1 / 706 (0.14%)
    0 / 697 (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
    Periodontitis
         subjects affected / exposed
    0 / 696 (0.00%)
    0 / 706 (0.00%)
    1 / 697 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
    alternative assessment type: Systematic
         subjects affected / exposed
    12 / 696 (1.72%)
    12 / 706 (1.70%)
    14 / 697 (2.01%)
         occurrences causally related to treatment / all
    0 / 13
    0 / 13
    0 / 14
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Pyelonephritis
         subjects affected / exposed
    1 / 696 (0.14%)
    0 / 706 (0.00%)
    0 / 697 (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
    0 / 696 (0.00%)
    0 / 706 (0.00%)
    2 / 697 (0.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Scrotal Abscess
         subjects affected / exposed
    0 / 696 (0.00%)
    1 / 706 (0.14%)
    0 / 697 (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
    Sepsis
         subjects affected / exposed
    1 / 696 (0.14%)
    1 / 706 (0.14%)
    1 / 697 (0.14%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Septic Shock
         subjects affected / exposed
    1 / 696 (0.14%)
    0 / 706 (0.00%)
    1 / 697 (0.14%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Tracheitis
         subjects affected / exposed
    0 / 696 (0.00%)
    1 / 706 (0.14%)
    0 / 697 (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
    Tuberculosis
         subjects affected / exposed
    0 / 696 (0.00%)
    1 / 706 (0.14%)
    0 / 697 (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 Respiratory Tract Infection
         subjects affected / exposed
    0 / 696 (0.00%)
    1 / 706 (0.14%)
    1 / 697 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Urinary Tract Infection
         subjects affected / exposed
    2 / 696 (0.29%)
    2 / 706 (0.28%)
    3 / 697 (0.43%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Urosepsis
         subjects affected / exposed
    0 / 696 (0.00%)
    1 / 706 (0.14%)
    0 / 697 (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
    Viral Upper Respiratory Tract Infection
         subjects affected / exposed
    1 / 696 (0.14%)
    0 / 706 (0.00%)
    0 / 697 (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
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    1 / 696 (0.14%)
    1 / 706 (0.14%)
    0 / 697 (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
    Diabetes Mellitus
         subjects affected / exposed
    2 / 696 (0.29%)
    0 / 706 (0.00%)
    1 / 697 (0.14%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diabetic Metabolic Decompensation
         subjects affected / exposed
    1 / 696 (0.14%)
    0 / 706 (0.00%)
    0 / 697 (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
    Hyperglycaemia
         subjects affected / exposed
    0 / 696 (0.00%)
    0 / 706 (0.00%)
    2 / 697 (0.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypokalaemia
         subjects affected / exposed
    1 / 696 (0.14%)
    0 / 706 (0.00%)
    0 / 697 (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
    Hyponatraemia
         subjects affected / exposed
    0 / 696 (0.00%)
    0 / 706 (0.00%)
    1 / 697 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Metabolic Disorder
         subjects affected / exposed
    1 / 696 (0.14%)
    0 / 706 (0.00%)
    0 / 697 (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
    Type 2 Diabetes Mellitus
         subjects affected / exposed
    1 / 696 (0.14%)
    0 / 706 (0.00%)
    0 / 697 (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: 2%
    Non-serious adverse events
    		 Rivaroxaban 15 mg Rivaroxaban 2.5 mg BID/15 mg vitamin K antagonist (VKA)
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    174 / 696 (25.00%)
    210 / 706 (29.75%)
    234 / 697 (33.57%)
    Injury, poisoning and procedural complications
    Contusion
         subjects affected / exposed
    13 / 696 (1.87%)
    35 / 706 (4.96%)
    25 / 697 (3.59%)
         occurrences all number
    17
    47
    32
    Subcutaneous Haematoma
         subjects affected / exposed
    2 / 696 (0.29%)
    10 / 706 (1.42%)
    14 / 697 (2.01%)
         occurrences all number
    9
    13
    15
    Vascular disorders
    Haematoma
         subjects affected / exposed
    21 / 696 (3.02%)
    31 / 706 (4.39%)
    61 / 697 (8.75%)
         occurrences all number
    21
    40
    85
    Hypertension
         subjects affected / exposed
    17 / 696 (2.44%)
    2 / 706 (0.28%)
    7 / 697 (1.00%)
         occurrences all number
    17
    2
    7
    Cardiac disorders
    Angina Pectoris
         subjects affected / exposed
    13 / 696 (1.87%)
    18 / 706 (2.55%)
    12 / 697 (1.72%)
         occurrences all number
    15
    22
    14
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    8 / 696 (1.15%)
    7 / 706 (0.99%)
    15 / 697 (2.15%)
         occurrences all number
    8
    7
    16
    General disorders and administration site conditions
    Oedema Peripheral
         subjects affected / exposed
    14 / 696 (2.01%)
    12 / 706 (1.70%)
    18 / 697 (2.58%)
         occurrences all number
    14
    13
    18
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    12 / 696 (1.72%)
    18 / 706 (2.55%)
    11 / 697 (1.58%)
         occurrences all number
    13
    19
    11
    Gingival Bleeding
         subjects affected / exposed
    17 / 696 (2.44%)
    16 / 706 (2.27%)
    18 / 697 (2.58%)
         occurrences all number
    19
    20
    20
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    27 / 696 (3.88%)
    21 / 706 (2.97%)
    18 / 697 (2.58%)
         occurrences all number
    31
    23
    21
    Epistaxis
         subjects affected / exposed
    67 / 696 (9.63%)
    59 / 706 (8.36%)
    82 / 697 (11.76%)
         occurrences all number
    82
    79
    108
    Skin and subcutaneous tissue disorders
    Ecchymosis
         subjects affected / exposed
    4 / 696 (0.57%)
    16 / 706 (2.27%)
    15 / 697 (2.15%)
         occurrences all number
    5
    21
    17
    Renal and urinary disorders
    Haematuria
         subjects affected / exposed
    18 / 696 (2.59%)
    14 / 706 (1.98%)
    14 / 697 (2.01%)
         occurrences all number
    21
    21
    14

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    06 Aug 2012
    Included modifications to inclusion and exclusion criteria; Increased the time window allowed for administration of first dose of study agent; modified the schedule for monitoring the international normalized ratio (INR) in subjects randomized to vitamin K antagonist (VKA) treatment in the dual antiplatelet therapy (DAPT) period; defined which creatinine laboratory test result was used to establish whether the rivaroxaban dose should be reduced for subjects with moderate renal impairment; and added collection of blood samples for exploratory pharmacokinetic and pharmacodynamic testing at selected study sites.
    10 Aug 2012
    Included a change to the concomitant medications to agree with current prescribing information for clopidogrel that recommended avoiding concomitant administration with omeprazole or esomeprazole.
    12 Dec 2012
    Included addition of a third treatment strategy group based on results from the What is the Optimal antiplatElet and anticoagulant therapy in patients with oral anticoagulation and coronary Stenting (WOEST) trial that was presented at 2012 European Society of Cardiology meeting; This new data suggested that dual therapy with warfarin plus clopidogrel caused less bleeding and lower rates of mortality than standard triple therapy with warfarin, clopidogrel, and acetylsalicylic acid (ASA) in patients undergoing percutaneous coronary intervention (PCI) who required anticoagulation; a third treatment strategy group with rivaroxaban plus clopidogrel administered for 12 months was added, the vitamin K antagonist (VKA) treatment strategy was changed to VKA for 12 months plus dual antiplatelet therapy (DAPT) followed by ASA, and changed the once-daily dose of rivaroxaban to 15 mg, and an alternative to clopidogrel, P2Y12 inhibitors (prasugrel or ticagrelor) were allowed.
    11 Oct 2013
    Included simplification of the timing of the first dose so that all treatment strategy groups had the first dose based only on time of sheath removal; Additional clarifications were made related to performing international normalized ratio (INR) tests in all subjects and only in those subjects randomized to VKA treatment strategy; Additional clarifications were made related to performing INR tests in all subjects and only in those subjects randomized to vitamin K antagonist (VKA) treatment strategy; The reporting of safety endpoint events of myocardial infarction (MI) and stent thrombosis was clarified; these events were not to be reported as serious adverse events (SAEs), rather, they would be captured as safety endpoint events in the CRF within 24 hours after the investigational staff’s knowledge of the event.

    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.
    First the stratification to either 1, 6 or 12 months of DAPT was based upon clinician choice and was not randomized. Secondly there was not sufficient power to definitively assess efficacy due to the modest number of adverse CV events.
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    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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