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Rivaroxaban Versus Aspirin in Secondary Prevention of Stroke and Prevention of Systemic Embolism in Patients With Recent Embolic Stroke of Undetermined Source (ESUS) (NAVIGATE ESUS)

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ClinicalTrials.gov Identifier: NCT02313909
Recruitment Status : Terminated (Study halted early due to no efficacy improvement over aspirin at an interim analysis and very little chance of showing overall benefit if study were completed)
First Posted : December 10, 2014
Results First Posted : January 9, 2019
Last Update Posted : January 9, 2019
Sponsor:
Collaborators:
Janssen Research & Development, LLC
Population Health Research Institute
Information provided by (Responsible Party):
Bayer

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Prevention
Condition Stroke
Interventions Drug: Rivaroxaban (Xarelto, BAY59-7939)
Drug: Acetylsalicylic acid (Aspirin, BAY1019036)
Other: Rivaroxaban-Placebo
Other: Aspirin-Placebo
Enrollment 7213
Recruitment Details Study was conducted at multiple centers in 31 countries between 23 December 2014 (first participant first visit) and 15 February 2018 (last participant last visit).
Pre-assignment Details Overall, 7582 participants were screened; of these 369 participants were screen failures. A total of 7213 participants were randomized, of which 92 never took study drug; 3562 were treated with rivaroxaban(Xarelto, BAY59-7939) /placebo and 3559 were treated with acetylsalicylic acid/placebo.
Arm/Group Title Rivaroxaban 15 mg OD Acetylsalicylic Acid 100 mg OD
Hide Arm/Group Description Subjects received rivaroxaban 15 mg immediate-release film-coated tablet and matching placebo of acetylsalicylic acid orally once daily (OD). Subjects received acetylsalicylic acid 100 mg enteric-coated tablet and matching placebo of rivaroxaban orally once daily (OD).
Period Title: Overall Study
Started 3609 3604
Treated 3562 3559
Completed 3552 3554
Not Completed 57 50
Reason Not Completed
Consent withdrawn by participant             33             33
Lost to Follow-up             24             17
Arm/Group Title Rivaroxaban 15 mg OD Acetylsalicylic Acid 100 mg OD Total
Hide Arm/Group Description Subjects received rivaroxaban 15 mg immediate-release film-coated tablet and matching placebo of acetylsalicylic acid orally once daily (OD). Subjects received acetylsalicylic acid 100 mg enteric-coated tablet and matching placebo of rivaroxaban orally once daily (OD). Total of all reporting groups
Overall Number of Baseline Participants 3609 3604 7213
Hide Baseline Analysis Population Description
Intention-to-treat analysis set included all randomized participants.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 3609 participants 3604 participants 7213 participants
66.9  (9.8) 66.9  (9.8) 66.9  (9.8)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3609 participants 3604 participants 7213 participants
Female
1377
  38.2%
1400
  38.8%
2777
  38.5%
Male
2232
  61.8%
2204
  61.2%
4436
  61.5%
Race (NIH/OMB)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3609 participants 3604 participants 7213 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
716
  19.8%
698
  19.4%
1414
  19.6%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
51
   1.4%
60
   1.7%
111
   1.5%
White
2613
  72.4%
2605
  72.3%
5218
  72.3%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
229
   6.3%
241
   6.7%
470
   6.5%
[1]
Measure Analysis Population Description: Intention-to-treat analysis set included all randomized participants.
Stroke or TIA (prior to qualifying stroke) or Other medical history   [1] 
Measure Type: Number
Unit of measure:  Count of participants
Number Analyzed 3609 participants 3604 participants 7213 participants
Stroke or TIA 620 643 1263
Other medical history 2989 2961 5950
[1]
Measure Description: TIA: Transient Ischemic Attack
Time from qualifying stroke to randomization   [1] 
Median (Inter-Quartile Range)
Unit of measure:  Days
Number Analyzed 3609 participants 3604 participants 7213 participants
38.0
(15.0 to 89.0)
36.0
(14.0 to 86.5)
37.0
(14.0 to 88.0)
[1]
Measure Analysis Population Description: Intention-to-treat analysis set included all randomized participants.
1.Primary Outcome
Title Incidence Rate of the Composite Efficacy Outcome (Adjudicated)
Hide Description Components of composite efficacy outcome (adjudicated) includes stroke (ischemic, hemorrhagic, and undefined stroke, TIA with positive neuroimaging) and systemic embolism. Incidence rate estimated as number of participants with incident events divided by cumulative at-risk time, where participant is no longer at risk once an incident event occurred.
Time Frame From randomization until the efficacy cut-off date (median 326 days)
Hide Outcome Measure Data
Hide Analysis Population Description
Intention-to-treat analysis set included all randomized participants. Participants who were evaluable for this measure at given time period for the arm were included in the category.
Arm/Group Title Rivaroxaban 15 mg OD Acetylsalicylic Acid 100 mg OD
Hide Arm/Group Description:
Subjects received rivaroxaban 15 mg immediate-release film-coated tablet and matching placebo of acetylsalicylic acid orally once daily (OD).
Subjects received acetylsalicylic acid 100 mg enteric-coated tablet and matching placebo of rivaroxaban orally once daily (OD).
Overall Number of Participants Analyzed 3609 3604
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: event/100 participant-years
5.14
(4.40 to 5.97)
4.78
(4.07 to 5.58)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rivaroxaban 15 mg OD, Acetylsalicylic Acid 100 mg OD
Comments Statistical analysis: Stroke + Systemic embolism: Risk reduction was estimated with the stratified Cox proportional hazards model. Hazard ratios (95% confidence interval) as compared to acetylsalicylic acid arm were reported. Rivaroxaban treatment was compared with the Acetylsalicylic acid control group using a stratified log-rank test. P-values (two-sided) as compared to acetylsalicylic acid arm were based on the log-rank test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.51884
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.07
Confidence Interval (2-Sided) 95%
0.87 to 1.33
Estimation Comments [Not Specified]
2.Primary Outcome
Title Incidence Rate of a Major Bleeding Event According to the International Society on Thrombosis and Haemostasis (ISTH) Criteria (Adjudicated)
Hide Description Major bleeding event (as per ISTH), defined as bleeding event that met at least one of following: fatal bleeding; symptomatic bleeding in a critical area or organ (intraarticular, intramuscular with compartment syndrome, intraocular, intraspinal, pericardial, or retroperitoneal); symptomatic intracranial haemorrhage; clinically overt bleeding associated with a recent decrease in the hemoglobin level of greater than or equal to (>=) 2 grams per decilitre (g/dL) (20 grams per liter [g/L]; 1.24 millimoles per liter [mmol/L]) compared to the most recent hemoglobin value available before the event; clinically overt bleeding leading to transfusion of 2 or more units of packed red blood cells or whole blood. The results were based on classification of events that have been positively adjudicated as major bleeding events. Incidence rate estimated as number of subjects with incident events divided by cumulative at-risk time, where subject is no longer at risk once an incident event occurred.
Time Frame From randomization until the efficacy cut-off date (median 326 days)
Hide Outcome Measure Data
Hide Analysis Population Description
Intention-to-treat analysis set included all randomized participants. Participants who were evaluable for this measure at given time period for the arm were included in the category.
Arm/Group Title Rivaroxaban 15 mg OD Acetylsalicylic Acid 100 mg OD
Hide Arm/Group Description:
Subjects received rivaroxaban 15 mg immediate-release film-coated tablet and matching placebo of acetylsalicylic acid orally once daily (OD).
Subjects received acetylsalicylic acid 100 mg enteric-coated tablet and matching placebo of rivaroxaban orally once daily (OD).
Overall Number of Participants Analyzed 3609 3604
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: event/100 participant-years
1.82
(1.39 to 2.33)
0.67
(0.42 to 1.00)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rivaroxaban 15 mg OD, Acetylsalicylic Acid 100 mg OD
Comments Statistical analysis: ISTH major bleeding events: Risk reduction was estimated with the stratified Cox proportional hazards model. Hazard ratios (95% confidence interval) as compared to acetylsalicylic acid arm were reported. Rivaroxaban treatment was compared with the Acetylsalicylic acid control group using a stratified log-rank test. P-values (two-sided) as compared to acetylsalicylic acid arm were based on the log-rank test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.00002
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 2.72
Confidence Interval (2-Sided) 95%
1.68 to 4.39
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Incidence Rate of Any of the Following: Cardiovascular Death, Recurrent Stroke, Systemic Embolism and Myocardial Infarction
Hide Description Incidence rate estimated as number of participants with incident events divided by cumulative at-risk time, where participant is no longer at risk once an incident event occurred. Cardiovascular death includes death due to hemorrhage and death with undetermined/unknown cause. Systemic embolism is defined as abrupt vascular insufficiency associated with clinical or radiological evidence of arterial occlusion in the absence of other likely mechanisms. The diagnosis of myocardial infarction requires the combination of: 1)evidence of myocardial necrosis (either changes in cardiac biomarkers or post-mortem pathological findings); and 2)supporting information derived from the clinical presentation, electrocardiographic changes, or the results of myocardial or coronary artery imaging.
Time Frame From randomization until the efficacy cut-off date (median 326 days)
Hide Outcome Measure Data
Hide Analysis Population Description
Intention-to-treat analysis set included all randomized participants. Participants who were evaluable for this measure at given time period for the arm were included in the category.
Arm/Group Title Rivaroxaban 15 mg OD Acetylsalicylic Acid 100 mg OD
Hide Arm/Group Description:
Subjects received rivaroxaban 15 mg immediate-release film-coated tablet and matching placebo of acetylsalicylic acid orally once daily (OD).
Subjects received acetylsalicylic acid 100 mg enteric-coated tablet and matching placebo of rivaroxaban orally once daily (OD).
Overall Number of Participants Analyzed 3609 3604
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: event/100 participant-years
6.20
(5.38 to 7.10)
5.85
(5.05 to 6.73)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rivaroxaban 15 mg OD, Acetylsalicylic Acid 100 mg OD
Comments Statistical analysis: Risk reduction was estimated with the stratified Cox proportional hazards model. Hazard ratios (95% confidence interval) as compared to acetylsalicylic acid arm were reported. Confidence intervals were calculated, if at least 1 event in each treatment arm existed. Rivaroxaban treatment was compared with the Acetylsalicylic acid control group using a stratified log-rank test. P-values (two-sided) as compared to acetylsalicylic acid arm were based on the log-rank test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.56922
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.06
Confidence Interval (2-Sided) 95%
0.87 to 1.29
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Incidence Rate of All-Cause Mortality
Hide Description All-cause mortality includes all deaths of participants due to any cause.
Time Frame From randomization until the efficacy cut-off date (median 326 days)
Hide Outcome Measure Data
Hide Analysis Population Description
Intention-to-treat analysis set included all randomized participants. Participants who were evaluable for this measure at given time period for the arm were included in the category.
Arm/Group Title Rivaroxaban 15 mg OD Acetylsalicylic Acid 100 mg OD
Hide Arm/Group Description:
Subjects received rivaroxaban 15 mg immediate-release film-coated tablet and matching placebo of acetylsalicylic acid orally once daily (OD).
Subjects received acetylsalicylic acid 100 mg enteric-coated tablet and matching placebo of rivaroxaban orally once daily (OD).
Overall Number of Participants Analyzed 3609 3604
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: event/100 participant-years
1.88
(1.45 to 2.40)
1.50
(1.12 to 1.97)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rivaroxaban 15 mg OD, Acetylsalicylic Acid 100 mg OD
Comments Risk reduction was estimated with the stratified Cox proportional hazards model. Hazard ratios (95% confidence interval) as compared to acetylsalicylic acid arm were reported. Confidence intervals were calculated, if at least 1 event in each treatment arm existed. Rivaroxaban treatment was compared with the Acetylsalicylic acid control group using a stratified log-rank test. P-values (two-sided) as compared to acetylsalicylic acid arm were based on the log-rank test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.22078
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.26
Confidence Interval (2-Sided) 95%
0.87 to 1.81
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Incidence Rate of the Following: Stroke, Ischemic Stroke, Disabling Stroke, Cardiovascular (CV) Death, Myocardial Infarction
Hide Description Disabling stroke is defined as stroke with modified Rankin score (mRS) greater than or equal to (>=) 4 as assessed by investigator. mRS spans 0-6, running from perfect health to death. A score of 0-3 indicates functional status ranging from no symptoms to "moderate disability" (defined in the mRS as requiring some help, but able to walk without assistance); mRS 4-6 indicates functional status ranging from "moderately severe disability" (unable to walk or to attend to own bodily needs without assistance)through to death. CV death includes death due to hemorrhage and death with undetermined/unknown cause. Diagnosis of myocardial infarction requires combination of: 1) evidence of myocardial necrosis either changes in cardiac biomarkers or post-mortem pathological findings); 2) supporting information derived from clinical presentation, electrocardiographic changes, or results of myocardial or coronary artery imaging.
Time Frame From randomization until the efficacy cut-off date (median 326 days)
Hide Outcome Measure Data
Hide Analysis Population Description
Intention-to-treat analysis set included all randomized participants. Participants who were evaluable for this measure at given time period for the arm were included in the category.
Arm/Group Title Rivaroxaban 15 mg OD Acetylsalicylic Acid 100 mg OD
Hide Arm/Group Description:
Subjects received rivaroxaban 15 mg immediate-release film-coated tablet and matching placebo of acetylsalicylic acid orally once daily (OD).
Subjects received acetylsalicylic acid 100 mg enteric-coated tablet and matching placebo of rivaroxaban orally once daily (OD).
Overall Number of Participants Analyzed 3609 3604
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: event/100 participant-years
Stroke
5.11
(4.37 to 5.93)
4.71
(4.01 to 5.51)
Ischemic stroke
4.71
(4.01 to 5.51)
4.56
(3.87 to 5.34)
Disabling stroke
1.20
(0.86 to 1.62)
0.84
(0.56 to 1.21)
CV death(includes death due to hemorrhage)
0.99
(0.68 to 1.38)
0.66
(0.42 to 1.00)
Myocardial infarction
0.49
(0.29 to 0.79)
0.67
(0.42 to 1.00)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rivaroxaban 15 mg OD, Acetylsalicylic Acid 100 mg OD
Comments Statistical analysis 1: Stroke: Risk reduction was estimated with the stratified Cox proportional hazards model. Hazard ratios (95% confidence interval) as compared to acetylsalicylic acid arm were reported. Rivaroxaban treatment was compared with the Acetylsalicylic acid control group using a stratified log-rank test. P-values (two-sided) as compared to acetylsalicylic acid arm were based on the log-rank test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.47970
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.08
Confidence Interval (2-Sided) 95%
0.87 to 1.34
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Rivaroxaban 15 mg OD, Acetylsalicylic Acid 100 mg OD
Comments Statistical analysis 2: Ischemic stroke: Risk reduction was estimated with the stratified Cox proportional hazards model. Hazard ratios (95% confidence interval) as compared to acetylsalicylic acid arm were reported. Rivaroxaban treatment was compared with the Acetylsalicylic acid control group using a stratified log-rank test. P-values (two-sided) as compared to acetylsalicylic acid arm were based on the log-rank test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.78738
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.03
Confidence Interval (2-Sided) 95%
0.83 to 1.29
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Rivaroxaban 15 mg OD, Acetylsalicylic Acid 100 mg OD
Comments Statistical analysis 3: Disabling stroke: Risk reduction was estimated with the stratified Cox proportional hazards model. Hazard ratios (95% confidence interval) as compared to acetylsalicylic acid arm were reported. Rivaroxaban treatment was compared with the Acetylsalicylic acid control group using a stratified log-rank test. P-values (two-sided) as compared to acetylsalicylic acid arm were based on the log-rank test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.14822
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.42
Confidence Interval (2-Sided) 95%
0.88 to 2.28
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Rivaroxaban 15 mg OD, Acetylsalicylic Acid 100 mg OD
Comments Statistical analysis 4:CV death: Risk reduction was estimated with the stratified Cox proportional hazards model. Hazard ratios (95% confidence interval) as compared to acetylsalicylic acid arm were reported. Rivaroxaban treatment was compared with the Acetylsalicylic acid control group using a stratified log-rank test. P-values (two-sided) as compared to acetylsalicylic acid arm were based on the log-rank test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.14051
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.48
Confidence Interval (2-Sided) 95%
0.87 to 2.52
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Rivaroxaban 15 mg OD, Acetylsalicylic Acid 100 mg OD
Comments Statistical analysis 5: Myocardial infarction: Risk reduction was estimated with the stratified Cox proportional hazards model. Hazard ratios (95% confidence interval) as compared to acetylsalicylic acid arm were reported. Rivaroxaban treatment was compared with the Acetylsalicylic acid control group using a stratified log-rank test. P-values (two-sided) as compared to acetylsalicylic acid arm were based on the log-rank test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.34284
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.74
Confidence Interval (2-Sided) 95%
0.39 to 1.38
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Incidence Rate of Life-Threatening Bleeding Events
Hide Description Life-threatening bleeding was defined as a subset of major bleeding that met at least one of the following criteria: 1) fatal bleeding; 2) symptomatic intracranial haemorrhage; 3) reduction in hemoglobin of at least 5 g/dl (50 g/l; 3.10 mmol/L); 4) transfusion of at least 4 units of packed red cells or whole blood; 5) associated with hypotension requiring the use of intravenous inotropic agents; 6) necessitated surgical intervention. Incidence rate estimated as number of participants with incident events divided by cumulative at-risk time, where participant is no longer at risk once an incident event occurred.
Time Frame From randomization until the efficacy cut-off date (median 326 days)
Hide Outcome Measure Data
Hide Analysis Population Description
Intention-to-treat analysis set included all randomized participants. Participants who were evaluable for this measure at given time period for the arm were included in the category.
Arm/Group Title Rivaroxaban 15 mg OD Acetylsalicylic Acid 100 mg OD
Hide Arm/Group Description:
Subjects received rivaroxaban 15 mg immediate-release film-coated tablet and matching placebo of acetylsalicylic acid orally once daily (OD).
Subjects received acetylsalicylic acid 100 mg enteric-coated tablet and matching placebo of rivaroxaban orally once daily (OD).
Overall Number of Participants Analyzed 3609 3604
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: event/100 participant-years
1.02
(0.71 to 1.42)
0.43
(0.24 to 0.72)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rivaroxaban 15 mg OD, Acetylsalicylic Acid 100 mg OD
Comments Statistical analysis: Risk reduction was estimated with the stratified Cox proportional hazards model. Hazard ratios (95% confidence interval) as compared to acetylsalicylic acid arm were reported. Rivaroxaban treatment was compared with the Acetylsalicylic acid control group using a stratified log-rank test. P-values (two-sided) as compared to acetylsalicylic acid arm were based on the log-rank test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.00443
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 2.34
Confidence Interval (2-Sided) 95%
1.28 to 4.29
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Incidence Rate of Clinically Relevant Non-Major Bleeding Events
Hide Description Non-major clinically relevant bleeding was defined as non-major overt bleeding but required medical attention (example: hospitalization, medical treatment for bleeding), and/or was associated with the study drug interruption of more than 14 days. The results were based on the outcome events at or after randomization until the efficacy cut-off date. Incidence rate estimated as number of participants with incident events divided by cumulative at-risk time, where participant is no longer at risk once an incident event occurred.
Time Frame From randomization until the efficacy cut-off date (median 326 days)
Hide Outcome Measure Data
Hide Analysis Population Description
Intention-to-treat analysis set included all randomized participants. Participants who were evaluable for this measure at given time period for the arm were included in the category.
Arm/Group Title Rivaroxaban 15 mg OD Acetylsalicylic Acid 100 mg OD
Hide Arm/Group Description:
Subjects received rivaroxaban 15 mg immediate-release film-coated tablet and matching placebo of acetylsalicylic acid orally once daily (OD).
Subjects received acetylsalicylic acid 100 mg enteric-coated tablet and matching placebo of rivaroxaban orally once daily (OD).
Overall Number of Participants Analyzed 3609 3604
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: event/100 participant-years
3.52
(2.91 to 4.21)
2.32
(1.84 to 2.90)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rivaroxaban 15 mg OD, Acetylsalicylic Acid 100 mg OD
Comments Statistical analysis: Risk reduction was estimated with the stratified Cox proportional hazards model. Hazard ratios (95% confidence interval) as compared to acetylsalicylic acid arm were reported. Rivaroxaban treatment was compared with the Acetylsalicylic acid control group using a stratified log-rank test. P-values (two-sided) as compared to acetylsalicylic acid arm were based on the log-rank test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.00451
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.51
Confidence Interval (2-Sided) 95%
1.13 to 2.00
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Incidence Rate of Intracranial Hemorrhage
Hide Description Intracranial hemorrhage included all bleeding events that occurred in intracerebral, sub arachnoidal as well as subdural or epidural sites. The below table displays results for all randomized participants and the outcomes at or after randomization until the efficacy cut-off date. Incidence rate estimated as number of participants with incident events divided by cumulative at-risk time, where participant is no longer at risk once an incident event occurred.
Time Frame From randomization until the efficacy cut-off date (median 326 days)
Hide Outcome Measure Data
Hide Analysis Population Description
Intention-to-treat analysis set included all randomized participants. Participants who were evaluable for this measure at given time period for the arm were included in the category.
Arm/Group Title Rivaroxaban 15 mg OD Acetylsalicylic Acid 100 mg OD
Hide Arm/Group Description:
Subjects received rivaroxaban 15 mg immediate-release film-coated tablet and matching placebo of acetylsalicylic acid orally once daily (OD).
Subjects received acetylsalicylic acid 100 mg enteric-coated tablet and matching placebo of rivaroxaban orally once daily (OD).
Overall Number of Participants Analyzed 3609 3604
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: event/100 participant-years
0.70
(0.45 to 1.04)
0.35
(0.18 to 0.61)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rivaroxaban 15 mg OD, Acetylsalicylic Acid 100 mg OD
Comments Statistical analysis 1: Risk reduction was estimated with the stratified Cox proportional hazards model. Hazard ratios (95% confidence interval) as compared to acetylsalicylic acid arm were reported. Rivaroxaban treatment was compared with the Acetylsalicylic acid control group using a stratified log-rank test. P-values (two-sided) as compared to acetylsalicylic acid arm were based on the log-rank test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.04409
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 2.01
Confidence Interval (2-Sided) 95%
1.00 to 4.02
Estimation Comments [Not Specified]
Time Frame From start of study drug administration until 2 days after the last dose of study drug, an average of 279 days
Adverse Event Reporting Description Safety analysis set included all randomized participants who received at least one dose of study drug.
 
Arm/Group Title Rivaroxaban 15 mg OD Acetylsalicylic Acid 100 mg OD
Hide Arm/Group Description Subjects received rivaroxaban 15 mg immediate-release film-coated tablet and matching placebo of acetylsalicylic acid orally once daily (OD). Subjects received acetylsalicylic acid 100 mg enteric-coated tablet and matching placebo of rivaroxaban orally once daily (OD).
All-Cause Mortality
Rivaroxaban 15 mg OD Acetylsalicylic Acid 100 mg OD
Affected / at Risk (%) Affected / at Risk (%)
Total   73/3562 (2.05%)      58/3559 (1.63%)    
Show Serious Adverse Events Hide Serious Adverse Events
Rivaroxaban 15 mg OD Acetylsalicylic Acid 100 mg OD
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   466/3562 (13.08%)      434/3559 (12.19%)    
Blood and lymphatic system disorders     
Anaemia * 1  8/3562 (0.22%)  8 3/3559 (0.08%)  3
Anaemia macrocytic * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Antiphospholipid syndrome * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Febrile neutropenia * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Iron deficiency anaemia * 1  4/3562 (0.11%)  4 1/3559 (0.03%)  1
Microcytic anaemia * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Pancytopenia * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Thrombocytopenia * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Thrombotic thrombocytopenic purpura * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Cardiac disorders     
Angina pectoris * 1  1/3562 (0.03%)  1 2/3559 (0.06%)  2
Aortic valve stenosis * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Arrhythmia * 1  2/3562 (0.06%)  2 1/3559 (0.03%)  1
Arrhythmia supraventricular * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Atrial fibrillation * 1  36/3562 (1.01%)  36 37/3559 (1.04%)  37
Atrial flutter * 1  5/3562 (0.14%)  5 3/3559 (0.08%)  3
Atrioventricular block complete * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Atrioventricular block second degree * 1  1/3562 (0.03%)  1 2/3559 (0.06%)  2
Bradycardia * 1  2/3562 (0.06%)  2 2/3559 (0.06%)  2
Cardiac amyloidosis * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Cardiac failure * 1  2/3562 (0.06%)  2 2/3559 (0.06%)  2
Cardiac failure chronic * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Cardiac failure congestive * 1  3/3562 (0.08%)  3 3/3559 (0.08%)  3
Conduction disorder * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Coronary artery disease * 1  3/3562 (0.08%)  3 2/3559 (0.06%)  2
Coronary artery occlusion * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Coronary artery stenosis * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Hypertensive heart disease * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Myocardial ischaemia * 1  1/3562 (0.03%)  1 3/3559 (0.08%)  3
Myocarditis * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Palpitations * 1  1/3562 (0.03%)  1 1/3559 (0.03%)  1
Pericardial effusion * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Sinus bradycardia * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Supraventricular tachycardia * 1  2/3562 (0.06%)  2 1/3559 (0.03%)  1
Ventricular tachycardia * 1  3/3562 (0.08%)  3 0/3559 (0.00%)  0
Atrial thrombosis * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Ventricular hypokinesia * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Coronary artery insufficiency * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Endocarditis noninfective * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Congenital, familial and genetic disorders     
Atrial septal defect * 1  1/3562 (0.03%)  1 2/3559 (0.06%)  2
Bicuspid aortic valve * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Hydrocele * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Pulmonary arteriovenous fistula * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Ear and labyrinth disorders     
Meniere's disease * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Vertigo * 1  2/3562 (0.06%)  2 2/3559 (0.06%)  2
Vertigo positional * 1  2/3562 (0.06%)  2 1/3559 (0.03%)  1
Endocrine disorders     
Basedow's disease * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Goitre * 1  1/3562 (0.03%)  1 1/3559 (0.03%)  1
Hyperparathyroidism * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Hyperthyroidism * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Thyroiditis subacute * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Eye disorders     
Blindness * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Cataract * 1  4/3562 (0.11%)  5 8/3559 (0.22%)  10
Diplopia * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Eyelid ptosis * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Glaucoma * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Macular oedema * 1  1/3562 (0.03%)  2 0/3559 (0.00%)  0
Retinal detachment * 1  0/3562 (0.00%)  0 2/3559 (0.06%)  2
Visual impairment * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Macular fibrosis * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Ophthalmic vein thrombosis * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Gastrointestinal disorders     
Abdominal pain * 1  2/3562 (0.06%)  2 2/3559 (0.06%)  2
Colitis ischaemic * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Constipation * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Crohn's disease * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Dental caries * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Diarrhoea * 1  2/3562 (0.06%)  2 2/3559 (0.06%)  2
Diverticulum intestinal * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Duodenal ulcer * 1  1/3562 (0.03%)  1 2/3559 (0.06%)  2
Dyspepsia * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Gastric haemorrhage * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Gastric ulcer * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Gastric ulcer haemorrhage * 1  0/3562 (0.00%)  0 2/3559 (0.06%)  2
Gastrointestinal fistula * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Gastrooesophageal reflux disease * 1  1/3562 (0.03%)  1 1/3559 (0.03%)  1
Haemorrhoids * 1  2/3562 (0.06%)  2 1/3559 (0.03%)  1
Hiatus hernia * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Ileus * 1  1/3562 (0.03%)  1 1/3559 (0.03%)  1
Inguinal hernia * 1  7/3562 (0.20%)  7 5/3559 (0.14%)  5
Intestinal obstruction * 1  2/3562 (0.06%)  2 2/3559 (0.06%)  2
Intestinal perforation * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Large intestinal ulcer * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Nausea * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Pancreatitis * 1  0/3562 (0.00%)  0 3/3559 (0.08%)  3
Pancreatitis acute * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Small intestinal obstruction * 1  1/3562 (0.03%)  1 1/3559 (0.03%)  1
Vomiting * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Lower gastrointestinal haemorrhage * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Pancreatolithiasis * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Large intestine polyp * 1  4/3562 (0.11%)  4 3/3559 (0.08%)  3
Gastric volvulus * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Abdominal hernia * 1  0/3562 (0.00%)  0 2/3559 (0.06%)  2
Gastric mucosal lesion * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Erosive duodenitis * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Rectal fissure * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
General disorders     
Asthenia * 1  0/3562 (0.00%)  0 3/3559 (0.08%)  3
Fatigue * 1  0/3562 (0.00%)  0 2/3559 (0.06%)  2
Gait disturbance * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Hernia * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Influenza like illness * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Oedema peripheral * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Pyrexia * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Peripheral swelling * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
General physical health deterioration * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Non-cardiac chest pain * 1  3/3562 (0.08%)  3 4/3559 (0.11%)  4
Multiple organ dysfunction syndrome * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Hepatobiliary disorders     
Bile duct stone * 1  4/3562 (0.11%)  4 1/3559 (0.03%)  1
Biliary colic * 1  1/3562 (0.03%)  1 1/3559 (0.03%)  1
Cholangitis * 1  0/3562 (0.00%)  0 2/3559 (0.06%)  2
Cholangitis acute * 1  0/3562 (0.00%)  0 2/3559 (0.06%)  2
Cholecystitis * 1  2/3562 (0.06%)  2 2/3559 (0.06%)  2
Cholecystitis acute * 1  3/3562 (0.08%)  3 4/3559 (0.11%)  4
Cholelithiasis * 1  6/3562 (0.17%)  6 3/3559 (0.08%)  3
Hepatic cirrhosis * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  2
Hepatitis * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Hepatitis acute * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Drug-induced liver injury * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Immune system disorders     
Anaphylactic reaction * 1  1/3562 (0.03%)  1 1/3559 (0.03%)  1
Anaphylactic shock * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Corneal graft rejection * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Hypersensitivity * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Infections and infestations     
Appendicitis * 1  2/3562 (0.06%)  2 1/3559 (0.03%)  1
Appendicitis perforated * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Atypical pneumonia * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Bacteraemia * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Brain abscess * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Bronchitis * 1  1/3562 (0.03%)  1 1/3559 (0.03%)  1
Cellulitis * 1  2/3562 (0.06%)  2 1/3559 (0.03%)  1
Clostridium difficile colitis * 1  0/3562 (0.00%)  0 2/3559 (0.06%)  2
Corneal abscess * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Cystitis * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Diabetic gangrene * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Diverticulitis * 1  2/3562 (0.06%)  2 1/3559 (0.03%)  1
Encephalitis viral * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Endophthalmitis * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Erysipelas * 1  1/3562 (0.03%)  1 2/3559 (0.06%)  2
Gastroenteritis * 1  6/3562 (0.17%)  6 3/3559 (0.08%)  3
Gastroenteritis viral * 1  2/3562 (0.06%)  2 0/3559 (0.00%)  0
Gastrointestinal infection * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Hepatitis A * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Infected skin ulcer * 1  1/3562 (0.03%)  1 1/3559 (0.03%)  1
Influenza * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Kidney infection * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Liver abscess * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Localised infection * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Lower respiratory tract infection * 1  1/3562 (0.03%)  1 1/3559 (0.03%)  1
Meningitis * 1  2/3562 (0.06%)  2 0/3559 (0.00%)  0
Orchitis * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Osteomyelitis * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Otitis externa * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Paronychia * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Peritoneal abscess * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Peritonitis * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Pneumonia * 1  14/3562 (0.39%)  14 14/3559 (0.39%)  14
Postoperative wound infection * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Pyelonephritis chronic * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Renal abscess * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Sepsis * 1  3/3562 (0.08%)  3 1/3559 (0.03%)  1
Septic shock * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Sinusitis * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Tooth abscess * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Upper respiratory tract infection * 1  1/3562 (0.03%)  1 1/3559 (0.03%)  1
Urinary tract infection * 1  6/3562 (0.17%)  6 6/3559 (0.17%)  7
Vestibular neuronitis * 1  1/3562 (0.03%)  1 1/3559 (0.03%)  1
Viral infection * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Urosepsis * 1  3/3562 (0.08%)  3 4/3559 (0.11%)  5
Rectal abscess * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Escherichia bacteraemia * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Pneumonia necrotising * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Abdominal infection * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Infective exacerbation of chronic obstructive airways disease * 1  3/3562 (0.08%)  4 0/3559 (0.00%)  0
Neurocysticercosis * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Enteritis infectious * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Abdominal abscess * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Bursitis infective * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Lung infection * 1  1/3562 (0.03%)  1 1/3559 (0.03%)  1
Perichondritis * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Respiratory tract infection * 1  3/3562 (0.08%)  3 1/3559 (0.03%)  1
Acarodermatitis * 1  1/3562 (0.03%)  2 0/3559 (0.00%)  0
Herpes zoster oticus * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Lower respiratory tract infection viral * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Biliary tract infection bacterial * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Pneumocystis jirovecii pneumonia * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Injury, poisoning and procedural complications     
Accidental overdose * 1  2/3562 (0.06%)  2 0/3559 (0.00%)  0
Anastomotic ulcer haemorrhage * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Ankle fracture * 1  3/3562 (0.08%)  3 2/3559 (0.06%)  2
Carbon monoxide poisoning * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Compression fracture * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Facial bones fracture * 1  1/3562 (0.03%)  1 1/3559 (0.03%)  1
Fall * 1  3/3562 (0.08%)  5 2/3559 (0.06%)  2
Femoral neck fracture * 1  6/3562 (0.17%)  6 0/3559 (0.00%)  0
Femur fracture * 1  5/3562 (0.14%)  5 2/3559 (0.06%)  2
Foot fracture * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Head injury * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Hip fracture * 1  1/3562 (0.03%)  1 5/3559 (0.14%)  5
Humerus fracture * 1  2/3562 (0.06%)  2 3/3559 (0.08%)  3
Intentional overdose * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Joint dislocation * 1  1/3562 (0.03%)  1 1/3559 (0.03%)  2
Laceration * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Ligament sprain * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Medication error * 1  2/3562 (0.06%)  2 0/3559 (0.00%)  0
Overdose * 1  0/3562 (0.00%)  0 2/3559 (0.06%)  2
Radius fracture * 1  2/3562 (0.06%)  2 0/3559 (0.00%)  0
Rib fracture * 1  1/3562 (0.03%)  1 2/3559 (0.06%)  2
Road traffic accident * 1  0/3562 (0.00%)  0 4/3559 (0.11%)  4
Spinal compression fracture * 1  3/3562 (0.08%)  3 3/3559 (0.08%)  3
Spinal fracture * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Subarachnoid haemorrhage * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Wrist fracture * 1  1/3562 (0.03%)  1 1/3559 (0.03%)  1
Traumatic fracture * 1  0/3562 (0.00%)  0 3/3559 (0.08%)  3
Cervical vertebral fracture * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Muscle strain * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Face injury * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Contusion * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Arterial restenosis * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Brain contusion * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Thermal burn * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Transplant failure * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  2
Limb injury * 1  1/3562 (0.03%)  1 2/3559 (0.06%)  2
Traumatic intracranial haemorrhage * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Upper limb fracture * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Ligament rupture * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Bone contusion * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Spinal column injury * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Pubis fracture * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Craniocerebral injury * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Meniscus injury * 1  0/3562 (0.00%)  0 3/3559 (0.08%)  3
Incorrect dosage administered * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Traumatic haemothorax * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Limb fracture * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Investigations     
Blood creatinine increased * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
C-reactive protein increased * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Eosinophil count increased * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Haemoglobin decreased * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Prostatic specific antigen increased * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Influenza A virus test positive * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Liver function test increased * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Metabolism and nutrition disorders     
Diabetes mellitus * 1  4/3562 (0.11%)  4 1/3559 (0.03%)  1
Diabetic ketoacidosis * 1  2/3562 (0.06%)  2 0/3559 (0.00%)  0
Failure to thrive * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Gout * 1  1/3562 (0.03%)  1 2/3559 (0.06%)  2
Hyperglycaemia * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Hyponatraemia * 1  1/3562 (0.03%)  2 6/3559 (0.17%)  6
Obesity * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Shock hypoglycaemic * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Diabetic complication * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Diabetic metabolic decompensation * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Adult failure to thrive * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Musculoskeletal and connective tissue disorders     
Arthralgia * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Back pain * 1  1/3562 (0.03%)  1 3/3559 (0.08%)  4
Fasciitis * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Gouty arthritis * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Groin pain * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Lumbar spinal stenosis * 1  2/3562 (0.06%)  2 0/3559 (0.00%)  0
Muscle spasms * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Musculoskeletal pain * 1  1/3562 (0.03%)  1 2/3559 (0.06%)  2
Myalgia * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Neck pain * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Osteoarthritis * 1  11/3562 (0.31%)  12 3/3559 (0.08%)  3
Osteonecrosis * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Pain in extremity * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Periarthritis * 1  1/3562 (0.03%)  1 1/3559 (0.03%)  1
Rheumatoid arthritis * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Rotator cuff syndrome * 1  1/3562 (0.03%)  1 1/3559 (0.03%)  1
Spinal column stenosis * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Spinal osteoarthritis * 1  1/3562 (0.03%)  1 1/3559 (0.03%)  1
Synovial cyst * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Myofascial pain syndrome * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Muscle tightness * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Intervertebral disc protrusion * 1  3/3562 (0.08%)  3 0/3559 (0.00%)  0
Musculoskeletal chest pain * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Limb discomfort * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Intervertebral disc disorder * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Plica syndrome * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Vertebral foraminal stenosis * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Acute lymphocytic leukaemia * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Adenocarcinoma * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Adenocarcinoma gastric * 1  2/3562 (0.06%)  2 2/3559 (0.06%)  2
Adenocarcinoma of colon * 1  2/3562 (0.06%)  2 0/3559 (0.00%)  0
B-cell lymphoma * 1  2/3562 (0.06%)  2 0/3559 (0.00%)  0
Basal cell carcinoma * 1  3/3562 (0.08%)  3 2/3559 (0.06%)  2
Bile duct adenocarcinoma * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Bladder cancer * 1  2/3562 (0.06%)  2 1/3559 (0.03%)  1
Bladder neoplasm * 1  1/3562 (0.03%)  1 1/3559 (0.03%)  1
Bladder transitional cell carcinoma * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Brain neoplasm malignant * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Cervix carcinoma * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Chronic lymphocytic leukaemia * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Colon cancer * 1  3/3562 (0.08%)  3 2/3559 (0.06%)  2
Colorectal cancer stage IV * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Essential thrombocythaemia * 1  1/3562 (0.03%)  1 1/3559 (0.03%)  1
Fallopian tube cancer * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Gallbladder cancer * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Gastric cancer * 1  1/3562 (0.03%)  1 1/3559 (0.03%)  1
Gastrointestinal carcinoma * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Hodgkin's disease * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Kaposi's sarcoma * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Lung adenocarcinoma * 1  1/3562 (0.03%)  1 2/3559 (0.06%)  2
Lung adenocarcinoma stage IV * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Lung carcinoma cell type unspecified stage IV * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Lymphoma * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Malignant melanoma * 1  1/3562 (0.03%)  2 0/3559 (0.00%)  0
Metastases to bone * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Myelodysplastic syndrome * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Non-Hodgkin's lymphoma * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Oesophageal adenocarcinoma * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Oesophageal carcinoma * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Oropharyngeal cancer * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Pancreatic carcinoma * 1  2/3562 (0.06%)  2 0/3559 (0.00%)  0
Pancreatic carcinoma metastatic * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Papillary thyroid cancer * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Parathyroid tumour * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Plasma cell myeloma * 1  1/3562 (0.03%)  1 1/3559 (0.03%)  1
Rectal adenocarcinoma * 1  1/3562 (0.03%)  1 2/3559 (0.06%)  2
Rectal cancer * 1  1/3562 (0.03%)  1 1/3559 (0.03%)  1
Rectal cancer stage III * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Spinal meningioma benign * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Squamous cell carcinoma of lung * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Squamous cell carcinoma of the tongue * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Transitional cell carcinoma * 1  3/3562 (0.08%)  3 0/3559 (0.00%)  0
Uterine leiomyoma * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Rectal adenoma * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Lung cancer metastatic * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Metastases to peritoneum * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Intestinal adenocarcinoma * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Neuroendocrine tumour * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Lung neoplasm malignant * 1  1/3562 (0.03%)  1 5/3559 (0.14%)  5
Pancreatic carcinoma stage IV * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Prostate cancer * 1  1/3562 (0.03%)  1 8/3559 (0.22%)  8
Benign bone neoplasm * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Brain neoplasm * 1  2/3562 (0.06%)  2 1/3559 (0.03%)  1
Renal neoplasm * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Oesophageal squamous cell carcinoma * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Pituitary tumour benign * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Non-small cell lung cancer * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Pancreatic neoplasm * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Lung neoplasm * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Thyroid cancer * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Renal cell carcinoma * 1  1/3562 (0.03%)  1 1/3559 (0.03%)  1
Metastatic uterine cancer * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Inflammatory pseudotumour * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Malignant neoplasm of unknown primary site * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Hepatic cancer * 1  2/3562 (0.06%)  2 0/3559 (0.00%)  0
Invasive breast carcinoma * 1  2/3562 (0.06%)  2 0/3559 (0.00%)  0
Nervous system disorders     
Amyotrophic lateral sclerosis * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Autonomic nervous system imbalance * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Brain stem haemorrhage * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Carotid artery stenosis * 1  2/3562 (0.06%)  2 2/3559 (0.06%)  2
Cerebellar haemorrhage * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Cerebral haemorrhage * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Cerebral venous thrombosis * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Cerebrovascular accident * 1  2/3562 (0.06%)  2 1/3559 (0.03%)  1
Chorea * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Demyelination * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Diabetic neuropathy * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Dizziness * 1  2/3562 (0.06%)  2 4/3559 (0.11%)  4
Dysarthria * 1  1/3562 (0.03%)  1 1/3559 (0.03%)  1
Epilepsy * 1  7/3562 (0.20%)  8 8/3559 (0.22%)  8
Facial paralysis * 1  0/3562 (0.00%)  0 2/3559 (0.06%)  2
Generalised tonic-clonic seizure * 1  1/3562 (0.03%)  1 1/3559 (0.03%)  1
Headache * 1  2/3562 (0.06%)  2 3/3559 (0.08%)  3
Hemiparesis * 1  1/3562 (0.03%)  1 2/3559 (0.06%)  2
Hypoaesthesia * 1  2/3562 (0.06%)  2 2/3559 (0.06%)  2
Intracranial aneurysm * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Loss of consciousness * 1  0/3562 (0.00%)  0 2/3559 (0.06%)  2
Migraine * 1  0/3562 (0.00%)  0 2/3559 (0.06%)  2
Migraine with aura * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Multiple sclerosis * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Myelopathy * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Nervous system disorder * 1  1/3562 (0.03%)  1 4/3559 (0.11%)  4
Paraesthesia * 1  2/3562 (0.06%)  2 1/3559 (0.03%)  1
Polyneuropathy * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Post herpetic neuralgia * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Presyncope * 1  2/3562 (0.06%)  2 2/3559 (0.06%)  2
Sciatica * 1  1/3562 (0.03%)  1 1/3559 (0.03%)  1
Seizure * 1  9/3562 (0.25%)  10 9/3559 (0.25%)  9
Status epilepticus * 1  0/3562 (0.00%)  0 2/3559 (0.06%)  2
Syncope * 1  10/3562 (0.28%)  10 8/3559 (0.22%)  8
Tension headache * 1  1/3562 (0.03%)  1 1/3559 (0.03%)  1
Transient global amnesia * 1  1/3562 (0.03%)  1 1/3559 (0.03%)  1
Vertebrobasilar insufficiency * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Cervical radiculopathy * 1  1/3562 (0.03%)  1 1/3559 (0.03%)  1
Thalamus haemorrhage * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Putamen haemorrhage * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Stroke in evolution * 1  0/3562 (0.00%)  0 2/3559 (0.06%)  2
Partial seizures * 1  5/3562 (0.14%)  5 2/3559 (0.06%)  2
Parkinson's disease * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Metabolic encephalopathy * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Cerebral artery stenosis * 1  1/3562 (0.03%)  1 1/3559 (0.03%)  1
Central pain syndrome * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Cerebral arteriosclerosis * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Post stroke seizure * 1  0/3562 (0.00%)  0 2/3559 (0.06%)  3
Hemianaesthesia * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Pseudostroke * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Hemiparaesthesia * 1  1/3562 (0.03%)  1 2/3559 (0.06%)  2
Focal dyscognitive seizures * 1  1/3562 (0.03%)  1 1/3559 (0.03%)  1
Product Issues     
Device malfunction * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Psychiatric disorders     
Adjustment disorder with mixed anxiety and depressed mood * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Alcohol abuse * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Alcoholism * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Anxiety * 1  2/3562 (0.06%)  2 2/3559 (0.06%)  2
Completed suicide * 1  0/3562 (0.00%)  0 2/3559 (0.06%)  2
Conversion disorder * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Delirium * 1  2/3562 (0.06%)  2 3/3559 (0.08%)  3
Depression * 1  3/3562 (0.08%)  3 1/3559 (0.03%)  1
Depression suicidal * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Disorientation * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Hallucination, visual * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Intentional self-injury * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Mania * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Obsessive-compulsive personality disorder * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Panic disorder * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Panic reaction * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Schizophrenia * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Somnambulism * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Suicide attempt * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Alcohol withdrawal syndrome * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Major depression * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Neurologic somatic symptom disorder * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Alcohol use disorder * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Renal and urinary disorders     
Acute prerenal failure * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Hydronephrosis * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Nephrolithiasis * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Renal colic * 1  0/3562 (0.00%)  0 2/3559 (0.06%)  3
Renal cyst * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Renal failure * 1  2/3562 (0.06%)  2 3/3559 (0.08%)  3
Renal haematoma * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Renal hypertension * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Urinary retention * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Costovertebral angle tenderness * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Renal impairment * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Chronic kidney disease * 1  2/3562 (0.06%)  2 1/3559 (0.03%)  1
Urethral stenosis * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Acute kidney injury * 1  4/3562 (0.11%)  4 6/3559 (0.17%)  6
Ureterolithiasis * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Reproductive system and breast disorders     
Benign prostatic hyperplasia * 1  4/3562 (0.11%)  4 2/3559 (0.06%)  2
Menorrhagia * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  2
Peyronie's disease * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Prostatitis * 1  2/3562 (0.06%)  2 0/3559 (0.00%)  0
Uterine prolapse * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Endometrial dysplasia * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Genital haemorrhage * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Acute pulmonary oedema * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Asthma * 1  1/3562 (0.03%)  1 1/3559 (0.03%)  1
Chronic obstructive pulmonary disease * 1  3/3562 (0.08%)  3 3/3559 (0.08%)  4
Dyspnoea * 1  1/3562 (0.03%)  1 1/3559 (0.03%)  1
Hiccups * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Idiopathic pulmonary fibrosis * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Lung disorder * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Pleural effusion * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Pneumonia aspiration * 1  3/3562 (0.08%)  3 0/3559 (0.00%)  0
Pulmonary embolism * 1  1/3562 (0.03%)  1 8/3559 (0.22%)  8
Pulmonary oedema * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Respiratory failure * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Sleep apnoea syndrome * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Pulmonary mass * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Bronchial disorder * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Skin and subcutaneous tissue disorders     
Dermatomyositis * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Erythema multiforme * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Psoriasis * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Rash * 1  1/3562 (0.03%)  1 1/3559 (0.03%)  1
Skin reaction * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Diabetic foot * 1  1/3562 (0.03%)  1 1/3559 (0.03%)  1
Surgical and medical procedures     
Atrial septal defect repair * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Finger amputation * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Vascular disorders     
Aortic aneurysm * 1  3/3562 (0.08%)  3 2/3559 (0.06%)  2
Aortic aneurysm rupture * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Aortic stenosis * 1  1/3562 (0.03%)  1 1/3559 (0.03%)  1
Embolism venous * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Hypertension * 1  4/3562 (0.11%)  4 6/3559 (0.17%)  6
Hypertensive crisis * 1  2/3562 (0.06%)  2 2/3559 (0.06%)  2
Hypotension * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Lymphoedema * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Orthostatic hypotension * 1  2/3562 (0.06%)  2 1/3559 (0.03%)  1
Peripheral ischaemia * 1  1/3562 (0.03%)  1 1/3559 (0.03%)  1
Peripheral vascular disorder * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Temporal arteritis * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Thrombophlebitis superficial * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Varicose vein * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Post thrombotic syndrome * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Deep vein thrombosis * 1  2/3562 (0.06%)  2 2/3559 (0.06%)  2
Peripheral artery occlusion * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Peripheral arterial occlusive disease * 1  5/3562 (0.14%)  5 5/3559 (0.14%)  6
May-Thurner syndrome * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Peripheral artery stenosis * 1  1/3562 (0.03%)  1 1/3559 (0.03%)  1
1
Term from vocabulary, MedDRA (20.1)
*
Indicates events were collected by non-systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Rivaroxaban 15 mg OD Acetylsalicylic Acid 100 mg OD
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   308/3562 (8.65%)      294/3559 (8.26%)    
Blood and lymphatic system disorders     
Anaemia * 1  2/3562 (0.06%)  2 2/3559 (0.06%)  2
Antiphospholipid syndrome * 1  2/3562 (0.06%)  2 0/3559 (0.00%)  0
Iron deficiency anaemia * 1  1/3562 (0.03%)  1 1/3559 (0.03%)  1
Thrombocytopenia * 1  2/3562 (0.06%)  2 1/3559 (0.03%)  1
Thrombocytosis * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Cardiac disorders     
Angina pectoris * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Atrial fibrillation * 1  60/3562 (1.68%)  60 60/3559 (1.69%)  60
Atrial flutter * 1  2/3562 (0.06%)  2 0/3559 (0.00%)  0
Atrial tachycardia * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Cardiac failure * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Cardiac failure congestive * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Coronary artery disease * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Myocardial ischaemia * 1  2/3562 (0.06%)  2 0/3559 (0.00%)  0
Palpitations * 1  3/3562 (0.08%)  3 1/3559 (0.03%)  1
Sinus arrhythmia * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Sinus tachycardia * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Supraventricular extrasystoles * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Supraventricular tachycardia * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Tachycardia * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Ventricular fibrillation * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Intracardiac thrombus * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Cardiac flutter * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Congenital, familial and genetic disorders     
Atrial septal defect * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Fabry's disease * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Factor V Leiden mutation * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Ear and labyrinth disorders     
Tinnitus * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Vertigo * 1  2/3562 (0.06%)  2 4/3559 (0.11%)  4
Vertigo positional * 1  2/3562 (0.06%)  2 2/3559 (0.06%)  2
Endocrine disorders     
Hypothyroidism * 1  1/3562 (0.03%)  1 1/3559 (0.03%)  1
Thyroiditis subacute * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Thyroid mass * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Eye disorders     
Cataract * 1  1/3562 (0.03%)  2 2/3559 (0.06%)  2
Conjunctival haemorrhage * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Diabetic retinopathy * 1  1/3562 (0.03%)  1 2/3559 (0.06%)  2
Dry eye * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Episcleritis * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Eyelid ptosis * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Keratitis * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Pterygium * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Retinal vein occlusion * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Vision blurred * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Conjunctival hyperaemia * 1  1/3562 (0.03%)  2 0/3559 (0.00%)  0
Gastrointestinal disorders     
Abdominal discomfort * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Abdominal pain * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Abdominal pain lower * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Abdominal pain upper * 1  5/3562 (0.14%)  5 7/3559 (0.20%)  7
Cheilitis * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Chronic gastritis * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Constipation * 1  2/3562 (0.06%)  2 1/3559 (0.03%)  1
Defaecation urgency * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Diarrhoea * 1  8/3562 (0.22%)  8 3/3559 (0.08%)  3
Dyspepsia * 1  2/3562 (0.06%)  2 3/3559 (0.08%)  4
Eructation * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Gastric ulcer * 1  0/3562 (0.00%)  0 2/3559 (0.06%)  2
Gastritis * 1  2/3562 (0.06%)  2 2/3559 (0.06%)  2
Gastritis erosive * 1  0/3562 (0.00%)  0 2/3559 (0.06%)  2
Gastrooesophageal reflux disease * 1  1/3562 (0.03%)  1 1/3559 (0.03%)  1
Gastrointestinal disorder * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Gingival bleeding * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Gingival swelling * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  2
Haemorrhoids * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Hyperchlorhydria * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Inflammatory bowel disease * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Inguinal hernia * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Lip swelling * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Nausea * 1  5/3562 (0.14%)  5 1/3559 (0.03%)  1
Oesophagitis * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Retching * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Toothache * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Vomiting * 1  2/3562 (0.06%)  2 4/3559 (0.11%)  4
Palatal disorder * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Colitis microscopic * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
General disorders     
Asthenia * 1  2/3562 (0.06%)  2 0/3559 (0.00%)  0
Chest discomfort * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Chest pain * 1  3/3562 (0.08%)  3 4/3559 (0.11%)  4
Chills * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Discomfort * 1  2/3562 (0.06%)  2 0/3559 (0.00%)  0
Fatigue * 1  2/3562 (0.06%)  2 3/3559 (0.08%)  3
Gait disturbance * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Malaise * 1  1/3562 (0.03%)  1 2/3559 (0.06%)  2
Oedema peripheral * 1  1/3562 (0.03%)  1 2/3559 (0.06%)  2
Peripheral swelling * 1  2/3562 (0.06%)  2 2/3559 (0.06%)  2
Non-cardiac chest pain * 1  2/3562 (0.06%)  2 0/3559 (0.00%)  0
Hepatobiliary disorders     
Biliary colic * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Hepatic function abnormal * 1  2/3562 (0.06%)  2 2/3559 (0.06%)  2
Hepatitis * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Hypertransaminasaemia * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Immune system disorders     
Hypersensitivity * 1  3/3562 (0.08%)  3 1/3559 (0.03%)  3
Allergy to arthropod sting * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Infections and infestations     
Bronchitis * 1  1/3562 (0.03%)  1 1/3559 (0.03%)  1
Cystitis * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Diarrhoea infectious * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Gastroenteritis * 1  3/3562 (0.08%)  3 1/3559 (0.03%)  1
Herpes zoster * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Influenza * 1  1/3562 (0.03%)  1 1/3559 (0.03%)  2
Lower respiratory tract infection * 1  1/3562 (0.03%)  2 0/3559 (0.00%)  0
Oesophageal candidiasis * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Pneumonia * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Pneumonia viral * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Upper respiratory tract infection * 1  2/3562 (0.06%)  2 1/3559 (0.03%)  2
Urinary tract infection * 1  3/3562 (0.08%)  3 4/3559 (0.11%)  4
Vaginal infection * 1  1/3562 (0.03%)  1 1/3559 (0.03%)  1
Vulvovaginitis trichomonal * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Helicobacter infection * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Lung infection * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Respiratory tract infection viral * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Alveolar osteitis * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Injury, poisoning and procedural complications     
Accident * 1  0/3562 (0.00%)  0 2/3559 (0.06%)  2
Alcohol poisoning * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Concussion * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Fall * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Foot fracture * 1  1/3562 (0.03%)  1 1/3559 (0.03%)  1
Head injury * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Humerus fracture * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Inappropriate schedule of drug administration * 1  1/3562 (0.03%)  2 0/3559 (0.00%)  0
Medication error * 1  10/3562 (0.28%)  10 9/3559 (0.25%)  9
Overdose * 1  2/3562 (0.06%)  2 0/3559 (0.00%)  0
Radius fracture * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Rib fracture * 1  2/3562 (0.06%)  2 0/3559 (0.00%)  0
Tendon rupture * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Face injury * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Contusion * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Post procedural haemorrhage * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Limb injury * 1  3/3562 (0.08%)  3 1/3559 (0.03%)  1
Upper limb fracture * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Drug administration error * 1  1/3562 (0.03%)  1 1/3559 (0.03%)  1
Incorrect dose administered * 1  6/3562 (0.17%)  6 4/3559 (0.11%)  4
Labelled drug-drug interaction medication error * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Skin wound * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Incorrect dosage administered * 1  2/3562 (0.06%)  2 1/3559 (0.03%)  1
Medication monitoring error * 1  1/3562 (0.03%)  1 3/3559 (0.08%)  3
Intentional product misuse * 1  2/3562 (0.06%)  2 1/3559 (0.03%)  1
Investigations     
Alanine aminotransferase increased * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Blood creatine phosphokinase increased * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Blood creatinine increased * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Coagulation factor VIII level increased * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Glomerular filtration rate decreased * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Haemoglobin decreased * 1  1/3562 (0.03%)  1 1/3559 (0.03%)  1
Heart rate increased * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Visual acuity tests abnormal * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Weight decreased * 1  1/3562 (0.03%)  1 2/3559 (0.06%)  2
Transaminases increased * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Blood alkaline phosphatase increased * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Hepatic enzyme increased * 1  1/3562 (0.03%)  1 1/3559 (0.03%)  1
Liver function test increased * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Metabolism and nutrition disorders     
Diabetes mellitus * 1  2/3562 (0.06%)  2 0/3559 (0.00%)  0
Electrolyte imbalance * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Gout * 1  1/3562 (0.03%)  1 1/3559 (0.03%)  1
Haemochromatosis * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Hypercholesterolaemia * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Hyperglycaemia * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Decreased appetite * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Type 2 diabetes mellitus * 1  2/3562 (0.06%)  2 1/3559 (0.03%)  1
Musculoskeletal and connective tissue disorders     
Arthralgia * 1  1/3562 (0.03%)  1 4/3559 (0.11%)  4
Arthritis * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Back pain * 1  4/3562 (0.11%)  4 3/3559 (0.08%)  3
Bursitis * 1  1/3562 (0.03%)  1 1/3559 (0.03%)  1
Chondrocalcinosis pyrophosphate * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Gouty arthritis * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Haemarthrosis * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Joint swelling * 1  1/3562 (0.03%)  1 1/3559 (0.03%)  1
Metatarsalgia * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Muscle spasms * 1  2/3562 (0.06%)  2 0/3559 (0.00%)  0
Muscular weakness * 1  2/3562 (0.06%)  2 2/3559 (0.06%)  2
Musculoskeletal pain * 1  1/3562 (0.03%)  1 4/3559 (0.11%)  4
Myalgia * 1  2/3562 (0.06%)  2 2/3559 (0.06%)  2
Myopathy * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Osteoarthritis * 1  2/3562 (0.06%)  2 1/3559 (0.03%)  1
Osteochondrosis * 1  1/3562 (0.03%)  1 1/3559 (0.03%)  1
Pain in extremity * 1  3/3562 (0.08%)  3 1/3559 (0.03%)  1
Periostitis * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Plantar fasciitis * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Spinal osteoarthritis * 1  0/3562 (0.00%)  0 2/3559 (0.06%)  2
Synovial cyst * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Tendonitis * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Tenosynovitis * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Limb mass * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Basosquamous carcinoma * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Breast cancer * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Breast neoplasm * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Essential thrombocythaemia * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Metastases to bone * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Superficial spreading melanoma stage unspecified * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Nervous system disorders     
Amnesia * 1  1/3562 (0.03%)  1 1/3559 (0.03%)  1
Aphasia * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Cerebrovascular accident * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Dementia * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Dizziness * 1  5/3562 (0.14%)  6 7/3559 (0.20%)  7
Dizziness postural * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Dysarthria * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Dysgeusia * 1  1/3562 (0.03%)  1 2/3559 (0.06%)  2
Epilepsy * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Facial paralysis * 1  1/3562 (0.03%)  1 1/3559 (0.03%)  1
Headache * 1  10/3562 (0.28%)  10 8/3559 (0.22%)  9
Hypoaesthesia * 1  1/3562 (0.03%)  1 3/3559 (0.08%)  3
Lethargy * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Migraine * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Paraesthesia * 1  1/3562 (0.03%)  1 1/3559 (0.03%)  1
Parkinsonism * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Presyncope * 1  1/3562 (0.03%)  1 2/3559 (0.06%)  2
Sciatica * 1  2/3562 (0.06%)  2 0/3559 (0.00%)  0
Seizure * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Sensory disturbance * 1  0/3562 (0.00%)  0 1/3559 (0.03%)  1
Somnolence * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Speech disorder * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Syncope * 1  2/3562 (0.06%)  2 3/3559 (0.08%)  4
Vertebral artery occlusion * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Cervical radiculopathy * 1  1/3562 (0.03%)  1 0/3559 (0.00%)  0
Hyposmia * 1