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    Clinical Trial Results:
    A Randomised, Double-Blind, Placebo-Controlled, International, Multicentre, Phase III Study to Investigate the Efficacy and Safety of Ticagrelor and ASA Compared with ASA in the Prevention of Stroke and Death in Patients with Acute Ischaemic Stroke or Transient Ischaemic Attack

    Summary
    EudraCT number
    		 2016-004232-37
    Trial protocol
    		 SE   CZ   HU   BG   FR   DE   ES   BE   PL   SK   IT   RO  
    Global end of trial date
    13 Dec 2019

    Results information
    Results version number
    		 v1(current)
    This version publication date
    04 Dec 2020
    First version publication date
    04 Dec 2020
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    D5134C00003
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03354429
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    AstraZeneca AB
    Sponsor organisation address
    Södertälje, Södertälje, Sweden, SE 151 85
    Public contact
    Information Center, AstraZeneca AB, 1 877-240-9479, Information.Center@astrazeneca.com
    Scientific contact
    Information Center, AstraZeneca AB, 1 877-240-9479, Information.Center@astrazeneca.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
    16 Jan 2020
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    13 Dec 2019
    Global end of trial reached?
    Yes
    Global end of trial date
    13 Dec 2019
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To demonstrate superior efficacy of ticagrelor and ASA compared with placebo and ASA in patients with acute ischaemic stroke (AIS) or TIA in the prevention of the composite of stroke and death at 30 days
    Protection of trial subjects
    Patients treated with aspirin as part of standard of care. An independent data monitoring committee was responsible for safeguarding the interests of the patients by assessing the benefit/risk profile of the intervention during the study, and for reviewing the overall conduct of the study
    Background therapy
    		 Aspirin as part of standard of care. Loading dose of 300-325 mg day 1, followed by 75-100 mg once daily
    Evidence for comparator
    		 -
    Actual start date of recruitment
    22 Jan 2018
    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: 98
    Country: Number of subjects enrolled
    Australia: 54
    Country: Number of subjects enrolled
    Belgium: 162
    Country: Number of subjects enrolled
    Brazil: 143
    Country: Number of subjects enrolled
    Bulgaria: 401
    Country: Number of subjects enrolled
    Canada: 23
    Country: Number of subjects enrolled
    China: 1480
    Country: Number of subjects enrolled
    Czechia: 147
    Country: Number of subjects enrolled
    France: 444
    Country: Number of subjects enrolled
    Germany: 192
    Country: Number of subjects enrolled
    Hong Kong: 69
    Country: Number of subjects enrolled
    Hungary: 692
    Country: Number of subjects enrolled
    India: 329
    Country: Number of subjects enrolled
    Italy: 154
    Country: Number of subjects enrolled
    Mexico: 105
    Country: Number of subjects enrolled
    Peru: 301
    Country: Number of subjects enrolled
    Poland: 406
    Country: Number of subjects enrolled
    Romania: 66
    Country: Number of subjects enrolled
    Russian Federation: 1293
    Country: Number of subjects enrolled
    Saudi Arabia: 27
    Country: Number of subjects enrolled
    Slovakia: 269
    Country: Number of subjects enrolled
    Korea, Republic of: 282
    Country: Number of subjects enrolled
    Spain: 857
    Country: Number of subjects enrolled
    Sweden: 157
    Country: Number of subjects enrolled
    Taiwan: 248
    Country: Number of subjects enrolled
    Thailand: 968
    Country: Number of subjects enrolled
    Ukraine: 350
    Country: Number of subjects enrolled
    Vietnam: 1299
    Worldwide total number of subjects
    11016
    EEA total number of subjects
    3947
    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)
    5308
    From 65 to 84 years
    5312
    85 years and over
    396

    Subject disposition

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    Recruitment
    Recruitment details
    		 414 study sites in 28 countries enrolled patients. The first patient was enrolled on 22 January 2018. The last patient visit took place on 13 December 2019.

    Pre-assignment
    Screening details
    		 11073 patients enrolled; 11016 patients randomised. 57 patients who were not randomised (patient did not meet inclusion/exclusion criteria n=52, patient decision n=5).

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Investigator, Monitor, Carer, Data analyst, Assessor, Subject

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 TICAGRELOR
    Arm description
    		 Ticagrelor 180 mg day 1, followed by 90 mg twice daily day 2-30
    Arm type
    		 Experimental

    Investigational medicinal product name
    Ticagrelor
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    180 mg loading dose followed by 90 mg twice daily

    Arm title
    		 PLACEBO
    Arm description
    		 Placebo 180 mg day 1, followed by 90 mg twice daily day 2-30
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo (matching ticagrelor)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Matching 180 mg loading dose followed by 90 mg twice daily

    Number of subjects in period 1
    		TICAGRELOR PLACEBO
    Started
    5523
    5493
    Completed
    5514
    5486
    Not completed
    9
    7
         Consent withdrawn by subject
    8
    7
         Lost to follow-up
    1
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    TICAGRELOR
    Reporting group description
    		 Ticagrelor 180 mg day 1, followed by 90 mg twice daily day 2-30

    Reporting group title
    PLACEBO
    Reporting group description
    		 Placebo 180 mg day 1, followed by 90 mg twice daily day 2-30

    Reporting group values
    		 TICAGRELOR PLACEBO Total
    Number of subjects
    		 5523 5493 11016
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0
        Newborns (0-27 days)
    		 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0
        Children (2-11 years)
    		 0 0 0
        Adolescents (12-17 years)
    		 0 0 0
        Adults (18-64 years)
    		 2676 2632 5308
        From 65-84 years
    		 2642 2670 5312
        85 years and over
    		 205 191 396
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    		 65.2 ( 11.0 ) 65.1 ( 11.1 ) -
    Sex: Female, Male
    Units: Participants
        Female
    		 2108 2171 4279
        Male
    		 3415 3322 6737
    Race/Ethnicity, Customized
    Units: Subjects
        White
    		 2973 2948 5921
        Black or African American
    		 21 32 53
        Asian
    		 2353 2339 4692
        Native Hawaiian or other Pacific Islander
    		 1 3 4
        American Indian or Alaska Native
    		 173 168 341
        Other
    		 2 3 5

    End points

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    End points reporting groups
    Reporting group title
    TICAGRELOR
    Reporting group description
    		 Ticagrelor 180 mg day 1, followed by 90 mg twice daily day 2-30

    Reporting group title
    PLACEBO
    Reporting group description
    		 Placebo 180 mg day 1, followed by 90 mg twice daily day 2-30

    Primary: Composite of subsequent stroke or death

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    End point title
    		 Composite of subsequent stroke or death
    End point description
    Participants with subsequent stroke or death
    End point type
    Primary
    End point timeframe
    From randomisation (day 1) to visit 3 (day 30-34)
    End point values
    		 TICAGRELOR PLACEBO
    Number of subjects analysed
    5523
    5493
    Units: Number of participants with event
    303
    362
    Statistical analysis title
    		 Prevention of the composite of stroke and death
    Statistical analysis description
    Time from randomisation to first subsequent stroke or death
    Comparison groups
    TICAGRELOR v PLACEBO
    Number of subjects included in analysis
    11016
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.015 [1]
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.83
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.71
         upper limit
    		 0.96
    Notes
    [1] - The hypothesis was tested at the 4.996% two-sided significance level to account for the planned interim analysis with the overall type I error preserved at 5%. A hierarchical test sequence was used to address the issue of multiple testing

    Secondary: Ischaemic stroke

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    End point title
    		 Ischaemic stroke
    End point description
    Number of participants with ischaemic stroke
    End point type
    Secondary
    End point timeframe
    From randomisation (day 1) to visit 3 (day 30-34)
    End point values
    		 TICAGRELOR PLACEBO
    Number of subjects analysed
    5523
    5493
    Units: Participants with event
    276
    345
    Statistical analysis title
    		 Prevention of ischaemic stroke
    Statistical analysis description
    Time from randomisation to first subsequent ischaemic stroke (including strokes classified as “Undetermined”)
    Comparison groups
    TICAGRELOR v PLACEBO
    Number of subjects included in analysis
    11016
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.004 [2]
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.79
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.68
         upper limit
    		 0.93
    Notes
    [2] - The hypothesis was tested at the 4.996% two-sided significance level to account for the planned interim analysis with the overall type I error preserved at 5%. A hierarchical test sequence was used to address the issue of multiple testing

    Secondary: The modified Rankin Scale (mRS) score >1 at Visit 3

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    End point title
    		 The modified Rankin Scale (mRS) score >1 at Visit 3
    End point description
    The modified Rankin Scale (mRS) is a scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. The scale runs from 0-6, running from perfect health without symptoms to death.0 - No symptoms,1 - No significant disability. Able to carry out all usual activities, despite some symptoms. 2 - Slight disability. Able to look after own affairs without assistance, but unable to carry out all previous activities. 3 - Moderate disability. Requires some help, but able to walk unassisted. 4 - Moderately severe disability. Unable to attend to own bodily needs without assistance, and unable to walk unassisted. 5 - Severe disability. Requires constant nursing care and attention, bedridden, incontinent. 6 - Dead.
    End point type
    Secondary
    End point timeframe
    Visit 3 (day 30-34)
    End point values
    		 TICAGRELOR PLACEBO
    Number of subjects analysed
    5386
    5333
    Units: Participants with mRS score >1
    1282
    1284
    Statistical analysis title
    		 Reduction of overall disability
    Statistical analysis description
    Modified Rankin Scale (mRS) score >1 at Visit 3
    Comparison groups
    TICAGRELOR v PLACEBO
    Number of subjects included in analysis
    10719
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.613 [3]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.98
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.89
         upper limit
    		 1.07
    Notes
    [3] - The hypothesis was tested at the 4.996% two-sided significance level to account for the planned interim analysis with the overall type I error preserved at 5%. A hierarchical test sequence was used to address the issue of multiple testing

    Other pre-specified: Bleeding event that fulfils SAE criteria and is categorised as GUSTO Severe

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    End point title
    		 Bleeding event that fulfils SAE criteria and is categorised as GUSTO Severe
    End point description
    Participants with bleeding event that fulfils SAE criteria and is categorised as GUSTO Severe
    End point type
    Other pre-specified
    End point timeframe
    From randomisation (day 1) to visit 3 (day 30-34)
    End point values
    		 TICAGRELOR PLACEBO
    Number of subjects analysed
    5523
    5493
    Units: Participants with event
    28
    7
    Statistical analysis title
    		 GUSTO Severe bleeding
    Statistical analysis description
    Time from randomisation to first bleeding event that fulfils SAE criteria and is categorised as GUSTO Severe
    Comparison groups
    TICAGRELOR v PLACEBO
    Number of subjects included in analysis
    11016
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.001
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    3.99
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.74
         upper limit
    		 9.14

    Other pre-specified: ICH or fatal bleeding event

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    End point title
    		 ICH or fatal bleeding event
    End point description
    Participants with ICH or fatal bleeding event
    End point type
    Other pre-specified
    End point timeframe
    From randomisation (day 1) to visit 3 (day 30-34)
    End point values
    		 TICAGRELOR PLACEBO
    Number of subjects analysed
    5523
    5493
    Units: Participants with event
    22
    6
    Statistical analysis title
    		 ICH or fatal bleeding
    Statistical analysis description
    Time from randomisation to first intracranial haemorrhage or fatal bleeding event
    Comparison groups
    TICAGRELOR v PLACEBO
    Number of subjects included in analysis
    11016
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.005
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    3.66
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.48
         upper limit
    		 9.02

    Other pre-specified: Bleeding event that fulfils SAE criteria and is categorised as GUSTO Moderate/Severe

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    End point title
    		 Bleeding event that fulfils SAE criteria and is categorised as GUSTO Moderate/Severe
    End point description
    Participants with bleeding event that fulfils SAE criteria and is categorised as GUSTO Moderate/Severe
    End point type
    Other pre-specified
    End point timeframe
    From randomisation (day 1) to visit 3 (day 30-34)
    End point values
    		 TICAGRELOR PLACEBO
    Number of subjects analysed
    5523
    5493
    Units: Participants with event
    36
    11
    Statistical analysis title
    		 GUSTO Moderate/Severe bleeding
    Statistical analysis description
    Time from randomisation to first bleeding event that fulfils SAE criteria and is categorised as GUSTO Moderate/Severe
    Comparison groups
    TICAGRELOR v PLACEBO
    Number of subjects included in analysis
    11016
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    3.27
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.67
         upper limit
    		 6.43

    Other pre-specified: Premature permanent discontinuation of IP due to bleeding

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    End point title
    		 Premature permanent discontinuation of IP due to bleeding
    End point description
    Participants with premature permanent discontinuation of IP due to bleeding
    End point type
    Other pre-specified
    End point timeframe
    From randomisation (day 1) to visit 3 (day 30-34)
    End point values
    		 TICAGRELOR PLACEBO
    Number of subjects analysed
    5523
    5493
    Units: Participants with event
    152
    32
    Statistical analysis title
    		 Permanent discontinuation of IP due to bleeding
    Statistical analysis description
    Time from randomisation to premature permanent discontinuation of IP due to bleeding
    Comparison groups
    TICAGRELOR v PLACEBO
    Number of subjects included in analysis
    11016
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    4.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 3.28
         upper limit
    		 7.02

    Adverse events

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    Adverse events information [1]
    Timeframe for reporting adverse events
    From randomisation (day 1) up to visit 3 (day 30-34)
    Adverse event reporting additional description
    Systematic assessment of serious adverse events and adverse events leading to premature permanent discontinuation of study drug. Other non-serious adverse events were not to be reported
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    22.1
    Reporting groups
    Reporting group title
    Ticagrelor 90 mg bd
    Reporting group description
    		 -

    Reporting group title
    Placebo
    Reporting group description
    		 -

    Notes
    [1] - There are no non-serious adverse events recorded for these results. It is expected that there will be at least one non-serious adverse event reported.
    Justification: Only serious adverse events and adverse events leading to discontinuation of study drug were to be collected. Hence, the number of non-serious events were limited and no preferred term reached the 5% threshold.
    Serious adverse events
    		 Ticagrelor 90 mg bd Placebo
    Total subjects affected by serious adverse events
         subjects affected / exposed
    571 / 5523 (10.34%)
    609 / 5493 (11.09%)
         number of deaths (all causes)
    36
    27
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Acute leukaemia
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Adenocarcinoma
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bladder cancer
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Brain neoplasm
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Brain neoplasm malignant
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac myxoma
         subjects affected / exposed
    0 / 5523 (0.00%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colon cancer
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colorectal adenocarcinoma
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Focal nodular hyperplasia
         subjects affected / exposed
    0 / 5523 (0.00%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastric cancer
         subjects affected / exposed
    1 / 5523 (0.02%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    Glioma
         subjects affected / exposed
    0 / 5523 (0.00%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatic cancer
         subjects affected / exposed
    0 / 5523 (0.00%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Lung adenocarcinoma
         subjects affected / exposed
    0 / 5523 (0.00%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung carcinoma cell type unspecified recurrent
         subjects affected / exposed
    0 / 5523 (0.00%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung neoplasm
         subjects affected / exposed
    0 / 5523 (0.00%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung neoplasm malignant
         subjects affected / exposed
    2 / 5523 (0.04%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Malignant mediastinal neoplasm
         subjects affected / exposed
    0 / 5523 (0.00%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Meningioma
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metastases to central nervous system
         subjects affected / exposed
    0 / 5523 (0.00%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metastatic gastric cancer
         subjects affected / exposed
    0 / 5523 (0.00%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myelofibrosis
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myeloproliferative neoplasm
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ovarian neoplasm
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Pancreatic carcinoma metastatic
         subjects affected / exposed
    0 / 5523 (0.00%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Phaeochromocytoma
         subjects affected / exposed
    0 / 5523 (0.00%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pharyngeal cancer
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pituitary tumour benign
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Prostate cancer
         subjects affected / exposed
    0 / 5523 (0.00%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Prostate cancer metastatic
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rectal adenocarcinoma
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rectal cancer
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal cancer
         subjects affected / exposed
    0 / 5523 (0.00%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal neoplasm
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Uterine cancer
         subjects affected / exposed
    0 / 5523 (0.00%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Vascular disorders
    Aortic dissection
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Aortic intramural haematoma
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Aortic stenosis
         subjects affected / exposed
    0 / 5523 (0.00%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arterial stenosis
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arteritis
         subjects affected / exposed
    0 / 5523 (0.00%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Circulatory collapse
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Deep vein thrombosis
         subjects affected / exposed
    0 / 5523 (0.00%)
    2 / 5493 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haematoma
         subjects affected / exposed
    0 / 5523 (0.00%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypertension
         subjects affected / exposed
    5 / 5523 (0.09%)
    5 / 5493 (0.09%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypertensive crisis
         subjects affected / exposed
    3 / 5523 (0.05%)
    4 / 5493 (0.07%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypertensive urgency
         subjects affected / exposed
    1 / 5523 (0.02%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypotension
         subjects affected / exposed
    0 / 5523 (0.00%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Penetrating aortic ulcer
         subjects affected / exposed
    0 / 5523 (0.00%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral arterial occlusive disease
         subjects affected / exposed
    1 / 5523 (0.02%)
    2 / 5493 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral ischaemia
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Subclavian artery stenosis
         subjects affected / exposed
    0 / 5523 (0.00%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vasculitis
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vena cava thrombosis
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Chest discomfort
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chest pain
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Death
         subjects affected / exposed
    4 / 5523 (0.07%)
    4 / 5493 (0.07%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 4
         deaths causally related to treatment / all
    0 / 4
    0 / 4
    Device related thrombosis
         subjects affected / exposed
    0 / 5523 (0.00%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General physical health deterioration
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Necrosis
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Non-cardiac chest pain
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    2 / 5523 (0.04%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sudden cardiac death
         subjects affected / exposed
    0 / 5523 (0.00%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Immune system disorders
    Anaphylactic reaction
         subjects affected / exposed
    1 / 5523 (0.02%)
    2 / 5493 (0.04%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anaphylactic shock
         subjects affected / exposed
    0 / 5523 (0.00%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Drug hypersensitivity
         subjects affected / exposed
    0 / 5523 (0.00%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Endometrial hyperplasia
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Menorrhagia
         subjects affected / exposed
    0 / 5523 (0.00%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Uterine haemorrhage
         subjects affected / exposed
    0 / 5523 (0.00%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Acute pulmonary oedema
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute respiratory failure
         subjects affected / exposed
    1 / 5523 (0.02%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Bronchitis chronic
         subjects affected / exposed
    2 / 5523 (0.04%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    0 / 5523 (0.00%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dyspnoea
         subjects affected / exposed
    3 / 5523 (0.05%)
    2 / 5493 (0.04%)
         occurrences causally related to treatment / all
    3 / 3
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Epistaxis
         subjects affected / exposed
    6 / 5523 (0.11%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    4 / 6
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemoptysis
         subjects affected / exposed
    1 / 5523 (0.02%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pleural effusion
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia aspiration
         subjects affected / exposed
    0 / 5523 (0.00%)
    2 / 5493 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Pneumonitis
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    9 / 5523 (0.16%)
    5 / 5493 (0.09%)
         occurrences causally related to treatment / all
    1 / 9
    0 / 5
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Pulmonary granuloma
         subjects affected / exposed
    0 / 5523 (0.00%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory failure
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory tract haemorrhage
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    1 / 5523 (0.02%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anxiety disorder
         subjects affected / exposed
    0 / 5523 (0.00%)
    2 / 5493 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Completed suicide
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Confusional state
         subjects affected / exposed
    2 / 5523 (0.04%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Conversion disorder
         subjects affected / exposed
    0 / 5523 (0.00%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Delirium
         subjects affected / exposed
    1 / 5523 (0.02%)
    3 / 5493 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hallucination, visual
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neuropsychiatric symptoms
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Organic brain syndrome
         subjects affected / exposed
    0 / 5523 (0.00%)
    2 / 5493 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Panic disorder
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychotic disorder
         subjects affected / exposed
    2 / 5523 (0.04%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sleep disorder
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Somatic symptom disorder
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Product issues
    Device dislocation
         subjects affected / exposed
    0 / 5523 (0.00%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations
    Blood glucose increased
         subjects affected / exposed
    0 / 5523 (0.00%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    International normalised ratio increased
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Occult blood positive
         subjects affected / exposed
    0 / 5523 (0.00%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Arterial bypass occlusion
         subjects affected / exposed
    0 / 5523 (0.00%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Clavicle fracture
         subjects affected / exposed
    0 / 5523 (0.00%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Femoral neck fracture
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Femur fracture
         subjects affected / exposed
    0 / 5523 (0.00%)
    2 / 5493 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Head injury
         subjects affected / exposed
    0 / 5523 (0.00%)
    2 / 5493 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hip fracture
         subjects affected / exposed
    0 / 5523 (0.00%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Open globe injury
         subjects affected / exposed
    0 / 5523 (0.00%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Periprocedural myocardial infarction
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post procedural haemorrhage
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rib fracture
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal compression fracture
         subjects affected / exposed
    0 / 5523 (0.00%)
    2 / 5493 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Subdural haematoma
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thermal burn
         subjects affected / exposed
    0 / 5523 (0.00%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Toxicity to various agents
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Traumatic intracranial haemorrhage
         subjects affected / exposed
    0 / 5523 (0.00%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular pseudoaneurysm
         subjects affected / exposed
    0 / 5523 (0.00%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Congenital, familial and genetic disorders
    Atrial septal defect
         subjects affected / exposed
    1 / 5523 (0.02%)
    4 / 5493 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular malformation
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Acute coronary syndrome
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute left ventricular failure
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Acute myocardial infarction
         subjects affected / exposed
    4 / 5523 (0.07%)
    5 / 5493 (0.09%)
         occurrences causally related to treatment / all
    0 / 4
    1 / 5
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    Angina unstable
         subjects affected / exposed
    2 / 5523 (0.04%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Aortic valve disease mixed
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arrhythmia
         subjects affected / exposed
    0 / 5523 (0.00%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arteriosclerosis coronary artery
         subjects affected / exposed
    0 / 5523 (0.00%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    18 / 5523 (0.33%)
    15 / 5493 (0.27%)
         occurrences causally related to treatment / all
    0 / 18
    0 / 17
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Atrial tachycardia
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrial thrombosis
         subjects affected / exposed
    4 / 5523 (0.07%)
    2 / 5493 (0.04%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrioventricular block complete
         subjects affected / exposed
    1 / 5523 (0.02%)
    2 / 5493 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrioventricular block second degree
         subjects affected / exposed
    3 / 5523 (0.05%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bradycardia
         subjects affected / exposed
    1 / 5523 (0.02%)
    2 / 5493 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac arrest
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac asthma
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac failure
         subjects affected / exposed
    0 / 5523 (0.00%)
    2 / 5493 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Cardiac failure acute
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac failure chronic
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Cardiac failure congestive
         subjects affected / exposed
    3 / 5523 (0.05%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac ventricular thrombosis
         subjects affected / exposed
    0 / 5523 (0.00%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardio-respiratory arrest
         subjects affected / exposed
    0 / 5523 (0.00%)
    2 / 5493 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Cardiomyopathy
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Congestive cardiomyopathy
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Coronary artery disease
         subjects affected / exposed
    2 / 5523 (0.04%)
    2 / 5493 (0.04%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Coronary artery occlusion
         subjects affected / exposed
    0 / 5523 (0.00%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intracardiac thrombus
         subjects affected / exposed
    2 / 5523 (0.04%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ischaemic cardiomyopathy
         subjects affected / exposed
    0 / 5523 (0.00%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mitral valve disease
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mitral valve disease mixed
         subjects affected / exposed
    0 / 5523 (0.00%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mitral valve incompetence
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    2 / 5523 (0.04%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myocardial ischaemia
         subjects affected / exposed
    1 / 5523 (0.02%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pericardial effusion
         subjects affected / exposed
    0 / 5523 (0.00%)
    2 / 5493 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Right ventricular failure
         subjects affected / exposed
    0 / 5523 (0.00%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Sinoatrial block
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sinus bradycardia
         subjects affected / exposed
    1 / 5523 (0.02%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sinus node dysfunction
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Supraventricular tachycardia
         subjects affected / exposed
    1 / 5523 (0.02%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ventricular extrasystoles
         subjects affected / exposed
    0 / 5523 (0.00%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ventricular fibrillation
         subjects affected / exposed
    0 / 5523 (0.00%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ventricular tachycardia
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Autonomic neuropathy
         subjects affected / exposed
    0 / 5523 (0.00%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Balance disorder
         subjects affected / exposed
    2 / 5523 (0.04%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Brain oedema
         subjects affected / exposed
    3 / 5523 (0.05%)
    3 / 5493 (0.05%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 3
    0 / 1
    Basal ganglia haemorrhage
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Brain stem stroke
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Brain stem syndrome
         subjects affected / exposed
    0 / 5523 (0.00%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Carotid arteriosclerosis
         subjects affected / exposed
    0 / 5523 (0.00%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Carotid artery occlusion
         subjects affected / exposed
    0 / 5523 (0.00%)
    2 / 5493 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Carotid artery stenosis
         subjects affected / exposed
    8 / 5523 (0.14%)
    7 / 5493 (0.13%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Carpal tunnel syndrome
         subjects affected / exposed
    0 / 5523 (0.00%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Central pain syndrome
         subjects affected / exposed
    0 / 5523 (0.00%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebellar infarction
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Cerebral artery stenosis
         subjects affected / exposed
    2 / 5523 (0.04%)
    2 / 5493 (0.04%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebral haemorrhage
         subjects affected / exposed
    4 / 5523 (0.07%)
    3 / 5493 (0.05%)
         occurrences causally related to treatment / all
    2 / 4
    2 / 3
         deaths causally related to treatment / all
    2 / 4
    1 / 2
    Cerebral infarction
         subjects affected / exposed
    6 / 5523 (0.11%)
    8 / 5493 (0.15%)
         occurrences causally related to treatment / all
    3 / 6
    0 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebral ischaemia
         subjects affected / exposed
    2 / 5523 (0.04%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebral venous sinus thrombosis
         subjects affected / exposed
    0 / 5523 (0.00%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebral venous thrombosis
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebrovascular accident
         subjects affected / exposed
    6 / 5523 (0.11%)
    7 / 5493 (0.13%)
         occurrences causally related to treatment / all
    0 / 6
    1 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebrovascular disorder
         subjects affected / exposed
    0 / 5523 (0.00%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Cerebrovascular insufficiency
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chronic inflammatory demyelinating polyradiculoneuropathy
         subjects affected / exposed
    0 / 5523 (0.00%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dizziness
         subjects affected / exposed
    2 / 5523 (0.04%)
    3 / 5493 (0.05%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dementia Alzheimer's type
         subjects affected / exposed
    0 / 5523 (0.00%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dysgraphia
         subjects affected / exposed
    0 / 5523 (0.00%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dysmetria
         subjects affected / exposed
    0 / 5523 (0.00%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Epilepsy
         subjects affected / exposed
    5 / 5523 (0.09%)
    3 / 5493 (0.05%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Guillain-Barre syndrome
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Haemorrhage intracranial
         subjects affected / exposed
    2 / 5523 (0.04%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemorrhagic stroke
         subjects affected / exposed
    7 / 5523 (0.13%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    5 / 7
    0 / 0
         deaths causally related to treatment / all
    4 / 6
    0 / 0
    Haemorrhagic transformation stroke
         subjects affected / exposed
    8 / 5523 (0.14%)
    6 / 5493 (0.11%)
         occurrences causally related to treatment / all
    6 / 8
    4 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Headache
         subjects affected / exposed
    0 / 5523 (0.00%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hemianaesthesia
         subjects affected / exposed
    0 / 5523 (0.00%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hemiparesis
         subjects affected / exposed
    0 / 5523 (0.00%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatic encephalopathy
         subjects affected / exposed
    0 / 5523 (0.00%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hydrocephalus
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypoaesthesia
         subjects affected / exposed
    1 / 5523 (0.02%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypoglycaemic seizure
         subjects affected / exposed
    0 / 5523 (0.00%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intracranial aneurysm
         subjects affected / exposed
    1 / 5523 (0.02%)
    2 / 5493 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ischaemic cerebral infarction
         subjects affected / exposed
    4 / 5523 (0.07%)
    6 / 5493 (0.11%)
         occurrences causally related to treatment / all
    1 / 4
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ischaemic stroke
         subjects affected / exposed
    254 / 5523 (4.60%)
    324 / 5493 (5.90%)
         occurrences causally related to treatment / all
    19 / 258
    36 / 330
         deaths causally related to treatment / all
    0 / 8
    0 / 7
    Lacunar stroke
         subjects affected / exposed
    0 / 5523 (0.00%)
    2 / 5493 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lacunar infarction
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Loss of consciousness
         subjects affected / exposed
    2 / 5523 (0.04%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Memory impairment
         subjects affected / exposed
    0 / 5523 (0.00%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Migraine
         subjects affected / exposed
    0 / 5523 (0.00%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neurological symptom
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Paraesthesia
         subjects affected / exposed
    0 / 5523 (0.00%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Paresis
         subjects affected / exposed
    0 / 5523 (0.00%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Parkinson's disease
         subjects affected / exposed
    0 / 5523 (0.00%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Partial seizures
         subjects affected / exposed
    2 / 5523 (0.04%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post stroke seizure
         subjects affected / exposed
    0 / 5523 (0.00%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychomotor hyperactivity
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Seizure
         subjects affected / exposed
    4 / 5523 (0.07%)
    3 / 5493 (0.05%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Somnolence
         subjects affected / exposed
    0 / 5523 (0.00%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Status epilepticus
         subjects affected / exposed
    2 / 5523 (0.04%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Spondylitic myelopathy
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Stroke in evolution
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Subarachnoid haemorrhage
         subjects affected / exposed
    2 / 5523 (0.04%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Syncope
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tension headache
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thalamic infarction
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Transient ischaemic attack
         subjects affected / exposed
    12 / 5523 (0.22%)
    30 / 5493 (0.55%)
         occurrences causally related to treatment / all
    0 / 12
    3 / 31
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular dementia
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vertebral artery stenosis
         subjects affected / exposed
    2 / 5523 (0.04%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    0 / 5523 (0.00%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Iron deficiency anaemia
         subjects affected / exposed
    1 / 5523 (0.02%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lymphadenopathy mediastinal
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Normochromic normocytic anaemia
         subjects affected / exposed
    0 / 5523 (0.00%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Normocytic anaemia
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Polycythaemia
         subjects affected / exposed
    0 / 5523 (0.00%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spontaneous haematoma
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thrombocytopenia
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    Vertigo positional
         subjects affected / exposed
    2 / 5523 (0.04%)
    2 / 5493 (0.04%)
         occurrences causally related to treatment / all
    0 / 2
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vestibular ataxia
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Eye disorders
    Angle closure glaucoma
         subjects affected / exposed
    0 / 5523 (0.00%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diabetic retinopathy
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Idiopathic orbital inflammation
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Visual impairment
         subjects affected / exposed
    0 / 5523 (0.00%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Constipation
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diverticular perforation
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Duodenal ulcer haemorrhage
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dyspepsia
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dysphagia
         subjects affected / exposed
    1 / 5523 (0.02%)
    2 / 5493 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastric disorder
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastritis
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal haemorrhage
         subjects affected / exposed
    6 / 5523 (0.11%)
    6 / 5493 (0.11%)
         occurrences causally related to treatment / all
    5 / 6
    3 / 6
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Gingival bleeding
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemorrhoidal haemorrhage
         subjects affected / exposed
    1 / 5523 (0.02%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Inguinal hernia
         subjects affected / exposed
    0 / 5523 (0.00%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lower gastrointestinal haemorrhage
         subjects affected / exposed
    3 / 5523 (0.05%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    1 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Melaena
         subjects affected / exposed
    2 / 5523 (0.04%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oesophageal haemorrhage
         subjects affected / exposed
    2 / 5523 (0.04%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oesophageal ulcer haemorrhage
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatitis chronic
         subjects affected / exposed
    0 / 5523 (0.00%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rectal haemorrhage
         subjects affected / exposed
    3 / 5523 (0.05%)
    2 / 5493 (0.04%)
         occurrences causally related to treatment / all
    3 / 3
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rectal ulcer haemorrhage
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Small intestinal haemorrhage
         subjects affected / exposed
    2 / 5523 (0.04%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Upper gastrointestinal haemorrhage
         subjects affected / exposed
    5 / 5523 (0.09%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    4 / 5
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    0 / 5523 (0.00%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Acute hepatic failure
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bile duct stone
         subjects affected / exposed
    0 / 5523 (0.00%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholangitis
         subjects affected / exposed
    1 / 5523 (0.02%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholecystitis
         subjects affected / exposed
    1 / 5523 (0.02%)
    2 / 5493 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholecystitis acute
         subjects affected / exposed
    1 / 5523 (0.02%)
    2 / 5493 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholelithiasis
         subjects affected / exposed
    0 / 5523 (0.00%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatic function abnormal
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatitis acute
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatocellular injury
         subjects affected / exposed
    0 / 5523 (0.00%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Angioedema
         subjects affected / exposed
    0 / 5523 (0.00%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ecchymosis
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rash
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urticaria
         subjects affected / exposed
    0 / 5523 (0.00%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    4 / 5523 (0.07%)
    2 / 5493 (0.04%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chronic kidney disease
         subjects affected / exposed
    2 / 5523 (0.04%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Cystitis haemorrhagic
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dysuria
         subjects affected / exposed
    0 / 5523 (0.00%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    End stage renal disease
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haematuria
         subjects affected / exposed
    8 / 5523 (0.14%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    6 / 8
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nephrolithiasis
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nephropathy toxic
         subjects affected / exposed
    1 / 5523 (0.02%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Prerenal failure
         subjects affected / exposed
    0 / 5523 (0.00%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal colic
         subjects affected / exposed
    1 / 5523 (0.02%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal failure
         subjects affected / exposed
    1 / 5523 (0.02%)
    3 / 5493 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal injury
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urethral stenosis
         subjects affected / exposed
    0 / 5523 (0.00%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary bladder polyp
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary retention
         subjects affected / exposed
    1 / 5523 (0.02%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Endocrine disorders
    Hypothyroidism
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    0 / 5523 (0.00%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bursitis
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Costochondritis
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gouty arthritis
         subjects affected / exposed
    0 / 5523 (0.00%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intervertebral disc protrusion
         subjects affected / exposed
    0 / 5523 (0.00%)
    2 / 5493 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Limb discomfort
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Muscular weakness
         subjects affected / exposed
    1 / 5523 (0.02%)
    2 / 5493 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sympathetic posterior cervical syndrome
         subjects affected / exposed
    0 / 5523 (0.00%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Anal abscess
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Appendicitis
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Brain abscess
         subjects affected / exposed
    0 / 5523 (0.00%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchitis
         subjects affected / exposed
    0 / 5523 (0.00%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    1 / 5523 (0.02%)
    3 / 5493 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Clostridium colitis
         subjects affected / exposed
    0 / 5523 (0.00%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Endocarditis
         subjects affected / exposed
    2 / 5523 (0.04%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Escherichia sepsis
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Escherichia urinary tract infection
         subjects affected / exposed
    0 / 5523 (0.00%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    0 / 5523 (0.00%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Gastrointestinal bacterial infection
         subjects affected / exposed
    1 / 5523 (0.02%)
    2 / 5493 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal infection
         subjects affected / exposed
    0 / 5523 (0.00%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infectious pleural effusion
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intervertebral discitis
         subjects affected / exposed
    0 / 5523 (0.00%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Klebsiella sepsis
         subjects affected / exposed
    0 / 5523 (0.00%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neurosyphilis
         subjects affected / exposed
    1 / 5523 (0.02%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peritonitis
         subjects affected / exposed
    0 / 5523 (0.00%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    25 / 5523 (0.45%)
    28 / 5493 (0.51%)
         occurrences causally related to treatment / all
    1 / 25
    2 / 29
         deaths causally related to treatment / all
    0 / 2
    0 / 4
    Pseudomembranous colitis
         subjects affected / exposed
    0 / 5523 (0.00%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyelonephritis acute
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyelonephritis chronic
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory syncytial virus infection
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory tract infection
         subjects affected / exposed
    1 / 5523 (0.02%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Sepsis
         subjects affected / exposed
    3 / 5523 (0.05%)
    5 / 5493 (0.09%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 5
         deaths causally related to treatment / all
    0 / 2
    0 / 1
    Septic shock
         subjects affected / exposed
    2 / 5523 (0.04%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tonsillitis
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tracheobronchitis
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tuberculosis
         subjects affected / exposed
    2 / 5523 (0.04%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Upper respiratory tract infection
         subjects affected / exposed
    0 / 5523 (0.00%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    6 / 5523 (0.11%)
    7 / 5493 (0.13%)
         occurrences causally related to treatment / all
    0 / 6
    2 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary tract infection enterococcal
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urosepsis
         subjects affected / exposed
    1 / 5523 (0.02%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Viral infection
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Wound infection
         subjects affected / exposed
    1 / 5523 (0.02%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diabetes mellitus inadequate control
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diabetic metabolic decompensation
         subjects affected / exposed
    0 / 5523 (0.00%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Electrolyte imbalance
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gout
         subjects affected / exposed
    2 / 5523 (0.04%)
    2 / 5493 (0.04%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypoglycaemia
         subjects affected / exposed
    3 / 5523 (0.05%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypokalaemia
         subjects affected / exposed
    1 / 5523 (0.02%)
    0 / 5493 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyponatraemia
         subjects affected / exposed
    3 / 5523 (0.05%)
    1 / 5493 (0.02%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Ticagrelor 90 mg bd Placebo
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    0 / 5523 (0.00%)
    0 / 5493 (0.00%)

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    08 May 2019
    Number of randomised subjects reduced from 13000 to 11000

    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.
    None

    Online references
    http://www.ncbi.nlm.nih.gov/pubmed/32668111
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