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The Stabilization Of pLaques usIng Darapladib-Thrombolysis In Myocardial Infarction 52 Trial (SOLID-TIMI 52)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01000727
Recruitment Status : Completed
First Posted : October 23, 2009
Results First Posted : August 10, 2017
Last Update Posted : August 10, 2017
Sponsor:
Collaborator:
The TIMI Study Group
Information provided by (Responsible Party):
GlaxoSmithKline

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Acute Coronary Syndrome
Interventions Drug: Darapladib 160 mg
Drug: Placebo
Other: Standard Therapy
Enrollment 13026
Recruitment Details The study was conducted at 868 centers in 36 countries: North America (282), Western Europe (210), Eastern Europe (166), Asia/Pacific (127), South America (83) during 07 December 2009 to 24 April 2014. A total of 13026 participants were randomized to the study.
Pre-assignment Details During the screening phase of the study, participants presenting with acute coronary syndrome (ACS) were randomized within 30 days. Approximately 77% of participants underwent percutaneous coronary intervention (PCI) for the qualifying event.
Arm/Group Title Placebo Darapladib 160 mg
Hide Arm/Group Description Participants were randomized to receive matching placebo once daily. Participants were randomized to receive darapladib 160 milligram (mg) enteric-coated tablets once daily.
Period Title: Overall Study
Started 6522 6504
Completed 6347 6328
Not Completed 175 176
Reason Not Completed
Lost to Follow-up             41             43
Withdrawal by Subject             111             109
Study closed/terminated             23             24
Arm/Group Title Placebo Darapladib 160 mg Total
Hide Arm/Group Description Participants were randomized to receive matching placebo once daily. Participants were randomized to receive darapladib 160 mg enteric-coated tablets once daily. Total of all reporting groups
Overall Number of Baseline Participants 6522 6504 13026
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 6522 participants 6504 participants 13026 participants
64.3  (9.50) 64.1  (9.52) 64.2  (9.51)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6522 participants 6504 participants 13026 participants
Female
1669
  25.6%
1657
  25.5%
3326
  25.5%
Male
4853
  74.4%
4847
  74.5%
9700
  74.5%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
 Number Analyzed 6522 participants 6504 participants 13026 participants
White - White/Caucasian/European Heritage 5329 5331 10660
Asian - East Asian Heritage 351 349 700
Asian - Central/South Asian Heritage 200 211 411
African American/African Heritage 160 155 315
White - Arabic/North African Heritage 138 119 257
Asian - South East Asian Heritage 123 116 239
Asian - Japanese Heritage 109 109 218
American Indian or Alaska Native 56 52 108
Mixed Race 43 52 95
Native Hawaiian or other Pacific Islander 9 5 14
Asian - Mixed Race 2 3 5
White - Mixed Race 2 2 4
1.Primary Outcome
Title Number of Participants With First Occurrence of Any Event in the Composite of Major Coronary Events During the Time Period for Follow-up (FU) of Cardiovascular (CV) Event
Hide Description Coronary heart disease (CHD) death=occurrence of a fatal myocardial infarction (MI), death caused by documented cardiac arrest, death resulting from heart failure in a participant with known CHD, death from other forms of acute/chronic CHD, unwitnessed death of unknown origin, or sudden death. Acute MI=evidence of myocardial necrosis in a clinical setting consistent with myocardial ischemia. Prior MI diagnosed post-randomization (e.g., silent MI)=the development of new pathological Q waves with/without symptoms OR imaging evidence of a region of loss of viable myocardium that is thinned and fails to contract, in the absence of a nonischemic cause (pre-event imaging data required for verification of new abnormality), OR pathological findings of a healed/healing MI. Urgent coronary revascularization (CR) for MI=ischemic discomfort at rest that prompted CR during the same hospitalization or resulted in hospital transfer for the purpose of CR.
Time Frame From randomization until the End-of-Treatment visit or the last date on which endpoints were able to be assessed (up to 3.80 years)
Hide Outcome Measure Data
Hide Analysis Population Description
All-Randomized intent-to-treat (ITT) Population consisted of all randomized participants.
Arm/Group Title Placebo Darapladib 160 mg
Hide Arm/Group Description:
Participants were randomized to receive matching placebo once daily.
Participants were randomized to receive darapladib 160 mg enteric-coated tablets once daily.
Overall Number of Participants Analyzed 6522 6504
Measure Type: Count of Participants
Unit of Measure: Participants
910
  14.0%
903
  13.9%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Darapladib 160 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.929
Comments Statistical significance of this p-value is based on the alpha-spending function of this study.
Method Cox Proportional Hazard Regression Model
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.00
Confidence Interval (2-Sided) 95.02%
0.91 to 1.09
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Number of Participants With First Occurrence of Any Component of the Composite of Major Adverse Cardiovascular Events (Cardiovascular [CV] Death, Non-fatal MI or Non-fatal Stroke) During the Time Period for Follow-up of CV Events
Hide Description CV death=death due to a CV cause, which included but was not limited to deaths resulting from stroke, arrhythmia, sudden death (witnessed/unwitnessed), MI, heart failure, pulmonary embolism, peripheral arterial disease, or complications of a CV procedure. Deaths not clearly attributable to non-CV causes are considered to be CV deaths. Acute MI=evidence of myocardial necrosis in a clinical setting consistent with myocardial ischemia. Prior MI diagnosed post-randomization (e.g., silent MI)=the development of new pathological Q waves with/without symptoms OR imaging evidence of a region of loss of viable myocardium that is thinned and fails to contract, in the absence of a non-ischemic cause (pre-event imaging data required for verification of new abnormality), OR pathological findings of a healed/healing MI. Stroke=presence of a new focal neurologic deficit thought to be of vascular origin, with signs/symptoms lasting >24 hours or results in death (in <24 hours).
Time Frame From randomization until the End-of-Treatment visit or the last date on which endpoints were able to be assessed (up to 3.80 years)
Hide Outcome Measure Data
Hide Analysis Population Description
All-Randomized ITT Population
Arm/Group Title Placebo Darapladib 160 mg
Hide Arm/Group Description:
Participants were randomized to receive matching placebo once daily.
Participants were randomized to receive darapladib 160 mg enteric-coated tablets once daily.
Overall Number of Participants Analyzed 6522 6504
Measure Type: Count of Participants
Unit of Measure: Participants
838
  12.8%
824
  12.7%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Darapladib 160 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.777
Comments Statistical significance of this p-value is based on the alpha-spending function of this study.
Method Cox Proportional Hazard Regression Model
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.99
Confidence Interval (2-Sided) 95.02%
0.90 to 1.09
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Number of Participants With Cardiovascular Death During the Time Period for Follow-up of Cardiovascular Events
Hide Description CV death is defined as a death due to a CV cause, which includes but is not limited to deaths resulting from stroke, arrhythmia, sudden death (witnessed/unwitnessed), MI, heart failure, pulmonary embolism, peripheral arterial disease, or complications of a CV procedure. Deaths not clearly attributable to non-CV causes are considered to be CV deaths.
Time Frame From randomization until the End-of-Treatment visit or the last date on which endpoints were able to be assessed (up to 3.80 years)
Hide Outcome Measure Data
Hide Analysis Population Description
All-Randomized ITT Population
Arm/Group Title Darapladib 160 mg Placebo
Hide Arm/Group Description:
Participants were randomized to receive matching placebo once daily.
Participants were randomized to receive darapladib 160 mg enteric-coated tablets once daily.
Overall Number of Participants Analyzed 6522 6504
Measure Type: Count of Participants
Unit of Measure: Participants
268
   4.1%
243
   3.7%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Darapladib 160 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.274
Comments Statistical significance of this p-value is based on the alpha-spending function of this study.
Method Cox Proportional Hazard Regression Model
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.91
Confidence Interval (2-Sided) 95%
0.76 to 1.08
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Number of Participants With First Occurrence of MI (Fatal/Nonfatal) During the Time Period for Follow-up of Cardiovascular Events
Hide Description Acute MI is defined as evidence of myocardial necrosis in a clinical setting consistent with myocardial ischemia. Prior MI diagnosed post-randomization (e.g., silent MI)=the development of new pathological Q waves with/without symptoms OR imaging evidence of a region of loss of viable myocardium that is thinned and fails to contract, in the absence of a non-ischemic cause (pre-event imaging data required for verification of new abnormality), OR pathological findings of a healed/healing MI.
Time Frame From randomization until the End-of-Treatment visit or the last date on which endpoints were able to be assessed (up to 3.80 years)
Hide Outcome Measure Data
Hide Analysis Population Description
All-Randomized ITT Population
Arm/Group Title Placebo Darapladib 160 mg
Hide Arm/Group Description:
Participants were randomized to receive matching placebo once daily.
Participants were randomized to receive darapladib 160 mg enteric-coated tablets once daily.
Overall Number of Participants Analyzed 6522 6504
Measure Type: Count of Participants
Unit of Measure: Participants
564
   8.6%
547
   8.4%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Darapladib 160 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.631
Comments [Not Specified]
Method Cox Proportional Hazard Regression Model
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.97
Confidence Interval (2-Sided) 95%
0.86 to 1.09
Estimation Comments A hazard ratio <1 indicates a lower risk with this treatment compared to Placebo
5.Secondary Outcome
Title Number of Participants With First Occurrence of Stroke (Fatal/Non-fatal) During the Time Period for Follow-up of Cardiovascular Events
Hide Description Stroke is defined as the presence of a new focal neurologic deficit thought to be of vascular origin, with signs/symptoms lasting >24 hours or results in death (in <24 hours).
Time Frame From randomization until the End-of-Treatment visit or the last date on which endpoints were able to be assessed (up to 3.80 years)
Hide Outcome Measure Data
Hide Analysis Population Description
All-Randomized ITT Population
Arm/Group Title Placebo Darapladib 160 mg
Hide Arm/Group Description:
Participants were randomized to receive matching placebo once daily.
Participants were randomized to receive darapladib 160 mg enteric-coated tablets once daily.
Overall Number of Participants Analyzed 6522 6504
Measure Type: Count of Participants
Unit of Measure: Participants
130
   2.0%
145
   2.2%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Darapladib 160 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.354
Comments [Not Specified]
Method Cox Proportional Hazard Regression Model
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.12
Confidence Interval (2-Sided) 95%
0.88 to 1.42
Estimation Comments A hazard ratio < 1 indicates a lower risk with this treatment compared to Placebo
6.Secondary Outcome
Title Number of Participants With CHD Death During the Time Period for Follow-up of Cardiovascular Events
Hide Description CHD death is defined as the occurrence of a fatal MI, death caused by documented cardiac arrest, death resulting from heart failure in a participant with known CHD, death from other forms of acute/chronic CHD, unwitnessed death of unknown origin, or sudden death.
Time Frame From randomization until the End-of-Treatment visit or the last date on which endpoints were able to be assessed (up to 3.80 years)
Hide Outcome Measure Data
Hide Analysis Population Description
All-Randomized ITT Population
Arm/Group Title Placebo Darapladib 160 mg
Hide Arm/Group Description:
Participants were randomized to receive matching placebo once daily.
Participants were randomized to receive darapladib 160 mg enteric-coated tablets once daily.
Overall Number of Participants Analyzed 6522 6504
Measure Type: Count of Participants
Unit of Measure: Participants
241
   3.7%
211
   3.2%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Darapladib 160 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.161
Comments [Not Specified]
Method Cox Proportional Hazard Regression Model
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.88
Confidence Interval (2-Sided) 95%
0.73 to 1.05
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Number of Participants With Urgent Coronary Revascularization for Myocardial Ischemia During the Time Period for Follow-up of Cardiovascular Events
Hide Description Urgent coronary revascularization for myocardial ischemia is defined as ischemic discomfort at rest that prompts coronary revascularization (PCI or coronary artery bypass graft [CABG]) during the same hospitalization or resulting in hospital transfer for the purpose of coronary revascularization. PCI is defined as any attempt at revascularization even if not successful (e.g., angioplasty, atherectomy or stenting).
Time Frame From randomization until the End-of-Treatment visit or the last date on which endpoints were able to be assessed (up to 3.80 years)
Hide Outcome Measure Data
Hide Analysis Population Description
All-Randomized ITT Population
Arm/Group Title Placebo Darapladib 160 mg
Hide Arm/Group Description:
Participants were randomized to receive matching placebo once daily.
Participants were randomized to receive darapladib 160 mg enteric-coated tablets once daily.
Overall Number of Participants Analyzed 6522 6504
Measure Type: Count of Participants
Unit of Measure: Participants
218
   3.3%
237
   3.6%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Darapladib 160 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.360
Comments [Not Specified]
Method Cox Proportional Hazard Regression Model
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.09
Confidence Interval (2-Sided) 95%
0.91 to 1.31
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Number of Participants With First Occurrence of Any Event in the Composite of Total Coronary Events (CHD Death, Non-fatal MI, Hospitalization for Unstable Angina, or Any Coronary Revascularization Procedure) During the Time Period for FU of CV Events
Hide Description CHD death, acute MI, and prior MI diagnosed post-randomization are defined in the primary endpoint (major coronary events). Hospitalization for unstable angina=one of the following, but not fulfilling the criteria for MI: ischemic discomfort at rest associated with electrocardiogram (ECG) changes leading to hospitalization; ischemic discomfort at rest regardless of ECG changes leading to hospitalization and revascularization during the same admission; ischemic discomfort at rest in hospital associated with ECG changes; ischemic discomfort at rest in hospital without ECG changes resulting in revascularization during the same admission. NOTE: The event was not considered to be unstable angina if, after invasive/non-invasive testing or other diagnostic testing, the discomfort was found not to be caused by myocardial ischemia. Coronary revascularization procedures exclude PCI planned prior to randomization but performed after randomization.
Time Frame From randomization until the End-of-Treatment visit or the last date on which endpoints were able to be assessed (up to 3.80 years)
Hide Outcome Measure Data
Hide Analysis Population Description
All-Randomized ITT Population
Arm/Group Title Placebo Darapladib 160 mg
Hide Arm/Group Description:
Participants were randomized to receive matching placebo once daily.
Participants were randomized to receive darapladib 160 mg enteric-coated tablets once daily.
Overall Number of Participants Analyzed 6522 6504
Measure Type: Count of Participants
Unit of Measure: Participants
1352
  20.7%
1290
  19.8%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Darapladib 160 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.202
Comments [Not Specified]
Method Cox Proportional Hazard Regression Model
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.95
Confidence Interval (2-Sided) 95%
0.88 to 1.03
Estimation Comments A hazard ratio <1 indicates a lower risk with this treatment compared to Placebo
9.Secondary Outcome
Title Number of Participants With First Occurrence of Any Coronary Revascularization Procedures (Excluding Coronary Revascularization Planned Prior to Randomization, But Performed After Randomization) During the Time Period for Follow-up of Cardiovascular Event
Hide Description All coronary revascularization procedures (except for PCI planned prior to randomization but performed after randomization) are included. Examples include coronary artery bypass graft, balloon angioplasty and stenting. The number of participants, with first occurrence of any coronary revascularization procedures, were reported.
Time Frame From randomization until the End-of-Treatment visit or the last date on which endpoints were able to be assessed (up to 3.80 years)
Hide Outcome Measure Data
Hide Analysis Population Description
All-Randomized ITT Population
Arm/Group Title Placebo Darapladib 160 mg
Hide Arm/Group Description:
Participants were randomized to receive matching placebo once daily.
Participants were randomized to receive darapladib 160 mg enteric-coated tablets once daily.
Overall Number of Participants Analyzed 6522 6504
Measure Type: Count of Participants
Unit of Measure: Participants
967
  14.8%
926
  14.2%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Darapladib 160 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.329
Comments [Not Specified]
Method Cox Proportional Hazard Regression Model
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.96
Confidence Interval (2-Sided) 95%
0.87 to 1.05
Estimation Comments [Not Specified]
10.Secondary Outcome
Title Number of Participants With First Occurrence of Any Component of the Composite of All-cause Mortality, Non-fatal MI, or Nonfatal Stroke During the Time Period for Follow-up of Cardiovascular Events
Hide Description Acute MI is defined as evidence of myocardial necrosis in a clinical setting consistent with myocardial ischemia. Prior MI diagnosed post-randomization (e.g., silent MI)=the development of new pathological Q waves with/without symptoms OR imaging evidence of a region of loss of viable myocardium that is thinned and fails to contract, in the absence of a non-ischemic cause (pre-event imaging data required for verification of new abnormality), OR pathological findings of a healed/healing MI. Stroke=presence of a new focal neurologic deficit thought to be of vascular origin, with signs/symptoms lasting >24 hours or results in death (in <24 hours).
Time Frame From randomization until the End-of-Treatment visit or the last date on which endpoints were able to be assessed (up to 3.80 years)
Hide Outcome Measure Data
Hide Analysis Population Description
All-Randomized ITT Population
Arm/Group Title Placebo Darapladib 160 mg
Hide Arm/Group Description:
Participants were randomized to receive matching placebo once daily.
Participants were randomized to receive darapladib 160 mg enteric-coated tablets once daily.
Overall Number of Participants Analyzed 6522 6504
Measure Type: Count of Participants
Unit of Measure: Participants
928
  14.2%
914
  14.1%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Darapladib 160 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.797
Comments [Not Specified]
Method Cox Proportional Hazard Regression Model
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.99
Confidence Interval (2-Sided) 95%
0.90 to 1.08
Estimation Comments [Not Specified]
11.Secondary Outcome
Title Number of Participants With First Occurrence of Any Event in the Composite of CHD Death and Non-fatal MI During the Time Period for Follow-up of Cardiovascular Events
Hide Description Acute MI is defined as evidence of myocardial necrosis in a clinical setting consistent with myocardial ischemia. Prior MI diagnosed post-randomization (e.g., silent MI)=the development of new pathological Q waves with/without symptoms OR imaging evidence of a region of loss of viable myocardium that is thinned and fails to contract, in the absence of a non-ischemic cause (pre-event imaging data required for verification of new abnormality), OR pathological findings of a healed/healing MI. CHD death is defined as the occurrence of a fatal MI, death caused by documented cardiac arrest, death resulting from heart failure in a participant with known CHD, death from other forms of acute/chronic CHD, unwitnessed death of unknown origin, or sudden death.
Time Frame From randomization until the End-of-Treatment visit or the last date on which endpoints were able to be assessed (up to 3.80 years)
Hide Outcome Measure Data
Hide Analysis Population Description
All-Randomized ITT Population
Arm/Group Title Placebo Darapladib 160 mg
Hide Arm/Group Description:
Participants were randomized to receive matching placebo once daily.
Participants were randomized to receive darapladib 160 mg enteric-coated tablets once daily.
Overall Number of Participants Analyzed 6522 6504
Measure Type: Count of Participants
Unit of Measure: Participants
725
  11.1%
701
  10.8%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Darapladib 160 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.546
Comments [Not Specified]
Method Cox Proportional Hazard Regression Model
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.97
Confidence Interval (2-Sided) 95%
0.87 to 1.07
Estimation Comments A hazard ratio <1 indicates a lower risk with this treatment compared to Placebo
12.Secondary Outcome
Title Number of Participants With All-cause Mortality During the Time Period for Vital Status
Hide Description Number of participants who died, during the vital status time-period were reported. The participants who were known to have died, date of death was used; for participants who completed the study the study completion date was used; for participants who withdrew from the study where vital status was ascertained , and are known to have not died , the last known date to be alive was used and for participants whom vital status was not ascertained, following study withdrawal the study withdrawal date was used.
Time Frame From randomization until the End-of-Treatment visit or the last date on which endpoints were able to be assessed (up to 3.80 years)
Hide Outcome Measure Data
Hide Analysis Population Description
All-Randomized ITT Population
Arm/Group Title Placebo Darapladib 160 mg
Hide Arm/Group Description:
Participants were randomized to receive matching placebo once daily.
Participants were randomized to receive darapladib 160 mg enteric-coated tablets once daily.
Overall Number of Participants Analyzed 6522 6504
Measure Type: Count of Participants
Unit of Measure: Participants
403
   6.2%
376
   5.8%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Darapladib 160 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.362
Comments [Not Specified]
Method Cox Proportional Hazard Regression Model
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.94
Confidence Interval (2-Sided) 95%
0.81 to 1.08
Estimation Comments [Not Specified]
Time Frame SAEs and non-serious AEs were collected from start of the study treatment up to 42 days after last dose of study treatment/FU visit.
Adverse Event Reporting Description SAEs and non-serious AEs were collected in members of the Safety Population, comprised of all randomized participants who received at least one dose of investigational product. Post-randomization AEs have an onset date that is on or after the randomization date. The safety population excluded 57 participants in the placebo group and 52 participants in the darapladib group who were randomized but did not receive study drug.
 
Arm/Group Title Placebo Darapladib 160 mg
Hide Arm/Group Description Participants were randomized to receive matching placebo once daily. Participants were randomized to receive darapladib 160 mg enteric-coated tablets once daily.
All-Cause Mortality
Placebo Darapladib 160 mg
Affected / at Risk (%) Affected / at Risk (%)
Total   403/6465 (6.23%)   376/6452 (5.83%) 
Hide Serious Adverse Events
Placebo Darapladib 160 mg
Affected / at Risk (%) Affected / at Risk (%)
Total   3011/6465 (46.57%)   2933/6452 (45.46%) 
Blood and lymphatic system disorders     
Agranulocytosis † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Anaemia † 1  43/6465 (0.67%)  49/6452 (0.76%) 
Anaemia macrocytic † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Aplastic anaemia † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Coagulopathy † 1  1/6465 (0.02%)  1/6452 (0.02%) 
Febrile neutropenia † 1  2/6465 (0.03%)  1/6452 (0.02%) 
Haemorrhagic anaemia † 1  3/6465 (0.05%)  3/6452 (0.05%) 
Heparin-induced thrombocytopenia † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Hypercoagulation † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Iron deficiency anaemia † 1  7/6465 (0.11%)  6/6452 (0.09%) 
Leukocytosis † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Lymphadenopathy mediastinal † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Lymphoid tissue hyperplasia † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Microcytic anaemia † 1  2/6465 (0.03%)  3/6452 (0.05%) 
Neutropenia † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Normochromic normocytic anaemia † 1  2/6465 (0.03%)  0/6452 (0.00%) 
Pancytopenia † 1  1/6465 (0.02%)  1/6452 (0.02%) 
Splenic infarction † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Thrombocytopenia † 1  2/6465 (0.03%)  2/6452 (0.03%) 
Cerebellar haemorrhage † 1  1/6465 (0.02%)  1/6452 (0.02%) 
Cardiac disorders     
Acute coronary syndrome † 1  8/6465 (0.12%)  11/6452 (0.17%) 
Acute left ventricular failure † 1  2/6465 (0.03%)  0/6452 (0.00%) 
Acute myocardial infarction † 1  446/6465 (6.90%)  432/6452 (6.70%) 
Angina pectoris † 1  272/6465 (4.21%)  266/6452 (4.12%) 
Angina unstable † 1  546/6465 (8.45%)  562/6452 (8.71%) 
Aortic valve incompetence † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Aortic valve stenosis † 1  3/6465 (0.05%)  2/6452 (0.03%) 
Arrhythmia † 1  3/6465 (0.05%)  1/6452 (0.02%) 
Arrhythmia supraventricular † 1  1/6465 (0.02%)  1/6452 (0.02%) 
Arteriosclerosis coronary artery † 1  5/6465 (0.08%)  11/6452 (0.17%) 
Arteriospasm coronary † 1  0/6465 (0.00%)  3/6452 (0.05%) 
Atrial fibrillation † 1  108/6465 (1.67%)  76/6452 (1.18%) 
Atrial flutter † 1  14/6465 (0.22%)  13/6452 (0.20%) 
Atrial tachycardia † 1  0/6465 (0.00%)  2/6452 (0.03%) 
Atrial thrombosis † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Atrioventricular block † 1  2/6465 (0.03%)  3/6452 (0.05%) 
Atrioventricular block complete † 1  14/6465 (0.22%)  5/6452 (0.08%) 
Atrioventricular block first degree † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Atrioventricular block second degree † 1  4/6465 (0.06%)  10/6452 (0.15%) 
Bradyarrhythmia † 1  0/6465 (0.00%)  3/6452 (0.05%) 
Bradycardia † 1  9/6465 (0.14%)  21/6452 (0.33%) 
Bundle branch block left † 1  2/6465 (0.03%)  0/6452 (0.00%) 
Cardiac aneurysm † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Cardiac arrest † 1  18/6465 (0.28%)  29/6452 (0.45%) 
Cardiac asthma † 1  2/6465 (0.03%)  2/6452 (0.03%) 
Cardiac discomfort † 1  1/6465 (0.02%)  2/6452 (0.03%) 
Cardiac failure † 1  176/6465 (2.72%)  170/6452 (2.63%) 
Cardiac failure acute † 1  21/6465 (0.32%)  20/6452 (0.31%) 
Cardiac failure chronic † 1  14/6465 (0.22%)  16/6452 (0.25%) 
Cardiac failure congestive † 1  101/6465 (1.56%)  107/6452 (1.66%) 
Cardiac tamponade † 1  2/6465 (0.03%)  1/6452 (0.02%) 
Cardio-respiratory arrest † 1  9/6465 (0.14%)  5/6452 (0.08%) 
Cardiogenic shock † 1  5/6465 (0.08%)  10/6452 (0.15%) 
Cardiomyopathy † 1  1/6465 (0.02%)  3/6452 (0.05%) 
Cardiopulmonary failure † 1  2/6465 (0.03%)  1/6452 (0.02%) 
Cardiorenal syndrome † 1  0/6465 (0.00%)  2/6452 (0.03%) 
Cardiovascular disorder † 1  11/6465 (0.17%)  10/6452 (0.15%) 
Cardiovascular insufficiency † 1  4/6465 (0.06%)  1/6452 (0.02%) 
Chronotropic incompetence † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Conduction disorder † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Coronary artery disease † 1  145/6465 (2.24%)  139/6452 (2.15%) 
Coronary artery dissection † 1  3/6465 (0.05%)  1/6452 (0.02%) 
Coronary artery insufficiency † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Coronary artery occlusion † 1  10/6465 (0.15%)  6/6452 (0.09%) 
Coronary artery perforation † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Coronary artery stenosis † 1  59/6465 (0.91%)  38/6452 (0.59%) 
Coronary artery thrombosis † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Dilatation ventricular † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Hypertensive heart disease † 1  1/6465 (0.02%)  1/6452 (0.02%) 
Interventricular septum rupture † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Intracardiac thrombus † 1  2/6465 (0.03%)  3/6452 (0.05%) 
Ischaemic cardiomyopathy † 1  5/6465 (0.08%)  8/6452 (0.12%) 
Left ventricular dysfunction † 1  1/6465 (0.02%)  3/6452 (0.05%) 
Left ventricular failure † 1  4/6465 (0.06%)  6/6452 (0.09%) 
Microvascular coronary artery disease † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Mitral valve disease † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Mitral valve incompetence † 1  5/6465 (0.08%)  6/6452 (0.09%) 
Myocardial fibrosis † 1  4/6465 (0.06%)  1/6452 (0.02%) 
Myocardial infarction † 1  61/6465 (0.94%)  45/6452 (0.70%) 
Myocardial ischaemia † 1  53/6465 (0.82%)  47/6452 (0.73%) 
Myocardial rupture † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Myopericarditis † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Nodal rhythm † 1  1/6465 (0.02%)  1/6452 (0.02%) 
Palpitations † 1  9/6465 (0.14%)  9/6452 (0.14%) 
Paroxysmal arrhythmia † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Pericardial effusion † 1  4/6465 (0.06%)  2/6452 (0.03%) 
Pericardial haemorrhage † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Pericarditis † 1  12/6465 (0.19%)  9/6452 (0.14%) 
Pleuropericarditis † 1  2/6465 (0.03%)  0/6452 (0.00%) 
Postinfarction angina † 1  8/6465 (0.12%)  4/6452 (0.06%) 
Prinzmetal angina † 1  1/6465 (0.02%)  4/6452 (0.06%) 
Pulseless electrical activity † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Restrictive cardiomyopathy † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Sick sinus syndrome † 1  10/6465 (0.15%)  7/6452 (0.11%) 
Sinoatrial block † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Sinus arrhythmia † 1  2/6465 (0.03%)  1/6452 (0.02%) 
Sinus bradycardia † 1  5/6465 (0.08%)  3/6452 (0.05%) 
Sinus tachycardia † 1  3/6465 (0.05%)  0/6452 (0.00%) 
Stress cardiomyopathy † 1  2/6465 (0.03%)  1/6452 (0.02%) 
Supraventricular extrasystoles † 1  1/6465 (0.02%)  1/6452 (0.02%) 
Supraventricular tachyarrhythmia † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Supraventricular tachycardia † 1  11/6465 (0.17%)  4/6452 (0.06%) 
Tachyarrhythmia † 1  3/6465 (0.05%)  0/6452 (0.00%) 
Tachycardia † 1  3/6465 (0.05%)  1/6452 (0.02%) 
Tachycardia paroxysmal † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Torsade de pointes † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Trifascicular block † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Ventricle rupture † 1  2/6465 (0.03%)  0/6452 (0.00%) 
Ventricular arrhythmia † 1  3/6465 (0.05%)  4/6452 (0.06%) 
Ventricular dyssynchrony † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Ventricular extrasystoles † 1  4/6465 (0.06%)  5/6452 (0.08%) 
Ventricular fibrillation † 1  14/6465 (0.22%)  12/6452 (0.19%) 
Ventricular tachyarrhythmia † 1  1/6465 (0.02%)  1/6452 (0.02%) 
Ventricular tachycardia † 1  28/6465 (0.43%)  19/6452 (0.29%) 
Congenital, familial and genetic disorders     
Atrial septal defect † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Gastrointestinal arteriovenous malformation † 1  1/6465 (0.02%)  1/6452 (0.02%) 
Odontogenic cyst † 1  2/6465 (0.03%)  0/6452 (0.00%) 
Phimosis † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Ear and labyrinth disorders     
Deafness † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Deafness neurosensory † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Ear haemorrhage † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Hearing impaired † 1  2/6465 (0.03%)  0/6452 (0.00%) 
Sudden hearing loss † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Tinnitus † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Vertigo † 1  8/6465 (0.12%)  8/6452 (0.12%) 
Vertigo positional † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Vestibular disorder † 1  1/6465 (0.02%)  1/6452 (0.02%) 
Endocrine disorders     
Adrenal insufficiency † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Autoimmune thyroiditis † 1  0/6465 (0.00%)  2/6452 (0.03%) 
Goitre † 1  4/6465 (0.06%)  2/6452 (0.03%) 
Hyperthyroidism † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Hypothyroidism † 1  0/6465 (0.00%)  2/6452 (0.03%) 
Primary hypothyroidism † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Eye disorders     
Accommodation disorder † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Age-related macular degeneration † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Amaurosis fugax † 1  1/6465 (0.02%)  1/6452 (0.02%) 
Blindness † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Blindness unilateral † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Cataract † 1  4/6465 (0.06%)  12/6452 (0.19%) 
Cataract nuclear † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Diabetic retinopathy † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Eye haemorrhage † 1  1/6465 (0.02%)  2/6452 (0.03%) 
Eyelid cyst † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Glaucoma † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Lens dislocation † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Macular hole † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Open angle glaucoma † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Optic neuropathy † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Retinal artery occlusion † 1  1/6465 (0.02%)  1/6452 (0.02%) 
Retinal detachment † 1  2/6465 (0.03%)  3/6452 (0.05%) 
Retinal haemorrhage † 1  2/6465 (0.03%)  0/6452 (0.00%) 
Retinoschisis † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Visual acuity reduced † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Visual impairment † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Vitreous haemorrhage † 1  1/6465 (0.02%)  2/6452 (0.03%) 
Gastrointestinal disorders     
Abdominal adhesions † 1  1/6465 (0.02%)  1/6452 (0.02%) 
Abdominal discomfort † 1  1/6465 (0.02%)  2/6452 (0.03%) 
Abdominal distension † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Abdominal hernia † 1  1/6465 (0.02%)  6/6452 (0.09%) 
Abdominal pain † 1  12/6465 (0.19%)  8/6452 (0.12%) 
Abdominal pain lower † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Abdominal pain upper † 1  9/6465 (0.14%)  8/6452 (0.12%) 
Abdominal strangulated hernia † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Abdominal wall haematoma † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Abnormal faeces † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Alcoholic pancreatitis † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Anal fissure † 1  3/6465 (0.05%)  0/6452 (0.00%) 
Anal fistula † 1  2/6465 (0.03%)  3/6452 (0.05%) 
Barrett's oesophagus † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Brunner's gland hyperplasia † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Caecitis † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Coeliac artery stenosis † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Colitis † 1  1/6465 (0.02%)  5/6452 (0.08%) 
Colitis ischaemic † 1  2/6465 (0.03%)  2/6452 (0.03%) 
Colitis ulcerative † 1  1/6465 (0.02%)  1/6452 (0.02%) 
Colonic pseudo-obstruction † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Constipation † 1  2/6465 (0.03%)  6/6452 (0.09%) 
Crohn's disease † 1  1/6465 (0.02%)  1/6452 (0.02%) 
Diabetic gastroparesis † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Diaphragmatic hernia † 1  2/6465 (0.03%)  0/6452 (0.00%) 
Diarrhoea † 1  8/6465 (0.12%)  14/6452 (0.22%) 
Diverticular perforation † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Diverticulum † 1  0/6465 (0.00%)  8/6452 (0.12%) 
Diverticulum intestinal † 1  5/6465 (0.08%)  4/6452 (0.06%) 
Diverticulum intestinal haemorrhagic † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Duodenal polyp † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Duodenal ulcer † 1  7/6465 (0.11%)  5/6452 (0.08%) 
Duodenal ulcer haemorrhage † 1  3/6465 (0.05%)  2/6452 (0.03%) 
Duodenitis † 1  1/6465 (0.02%)  2/6452 (0.03%) 
Duodenogastric reflux † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Dyspepsia † 1  5/6465 (0.08%)  7/6452 (0.11%) 
Dysphagia † 1  2/6465 (0.03%)  0/6452 (0.00%) 
Enteritis † 1  1/6465 (0.02%)  1/6452 (0.02%) 
Enterocele † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Enterocolitis † 1  2/6465 (0.03%)  1/6452 (0.02%) 
Enterovesical fistula † 1  2/6465 (0.03%)  1/6452 (0.02%) 
Erosive oesophagitis † 1  0/6465 (0.00%)  2/6452 (0.03%) 
Faeces discoloured † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Femoral hernia † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Food poisoning † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Gastric disorder † 1  0/6465 (0.00%)  4/6452 (0.06%) 
Gastric haemorrhage † 1  5/6465 (0.08%)  2/6452 (0.03%) 
Gastric perforation † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Gastric polyps † 1  2/6465 (0.03%)  0/6452 (0.00%) 
Gastric ulcer † 1  17/6465 (0.26%)  13/6452 (0.20%) 
Gastric ulcer haemorrhage † 1  2/6465 (0.03%)  2/6452 (0.03%) 
Gastritis † 1  16/6465 (0.25%)  10/6452 (0.15%) 
Gastritis atrophic † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Gastritis erosive † 1  3/6465 (0.05%)  3/6452 (0.05%) 
Gastritis haemorrhagic † 1  1/6465 (0.02%)  1/6452 (0.02%) 
Gastroduodenal ulcer † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Gastroduodenitis haemorrhagic † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Gastrointestinal disorder † 1  3/6465 (0.05%)  1/6452 (0.02%) 
Gastrointestinal haemorrhage † 1  26/6465 (0.40%)  18/6452 (0.28%) 
Gastrointestinal pain † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Gastrooesophageal reflux disease † 1  13/6465 (0.20%)  6/6452 (0.09%) 
Gastrooesophagitis † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Haematemesis † 1  3/6465 (0.05%)  3/6452 (0.05%) 
Haematochezia † 1  1/6465 (0.02%)  1/6452 (0.02%) 
Haemorrhagic erosive gastritis † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Haemorrhoidal haemorrhage † 1  2/6465 (0.03%)  2/6452 (0.03%) 
Haemorrhoids † 1  3/6465 (0.05%)  2/6452 (0.03%) 
Hiatus hernia † 1  4/6465 (0.06%)  5/6452 (0.08%) 
Hyperchlorhydria † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Ileal perforation † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Ileal stenosis † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Ileus † 1  3/6465 (0.05%)  3/6452 (0.05%) 
Ileus paralytic † 1  1/6465 (0.02%)  2/6452 (0.03%) 
Inguinal hernia † 1  17/6465 (0.26%)  16/6452 (0.25%) 
Inguinal hernia, obstructive † 1  2/6465 (0.03%)  2/6452 (0.03%) 
Intestinal haemorrhage † 1  2/6465 (0.03%)  2/6452 (0.03%) 
Intestinal infarction † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Intestinal ischaemia † 1  1/6465 (0.02%)  1/6452 (0.02%) 
Intestinal obstruction † 1  3/6465 (0.05%)  2/6452 (0.03%) 
Intestinal perforation † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Intestinal ulcer † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Intra-abdominal haemorrhage † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Irritable bowel syndrome † 1  1/6465 (0.02%)  2/6452 (0.03%) 
Large intestinal obstruction † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Large intestinal ulcer † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Large intestine perforation † 1  1/6465 (0.02%)  2/6452 (0.03%) 
Large intestine polyp † 1  8/6465 (0.12%)  7/6452 (0.11%) 
Lower gastrointestinal haemorrhage † 1  5/6465 (0.08%)  5/6452 (0.08%) 
Mallory-Weiss syndrome † 1  0/6465 (0.00%)  2/6452 (0.03%) 
Megacolon † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Melaena † 1  2/6465 (0.03%)  4/6452 (0.06%) 
Mesenteric artery thrombosis † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Mesenteric vein thrombosis † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Nausea † 1  6/6465 (0.09%)  5/6452 (0.08%) 
Obstruction gastric † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Odynophagia † 1  1/6465 (0.02%)  1/6452 (0.02%) 
Oesophageal disorder † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Oesophageal stenosis † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Oesophageal ulcer † 1  2/6465 (0.03%)  0/6452 (0.00%) 
Oesophagitis † 1  2/6465 (0.03%)  2/6452 (0.03%) 
Pancreatic disorder † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Pancreatic pseudocyst † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Pancreatitis † 1  7/6465 (0.11%)  4/6452 (0.06%) 
Pancreatitis acute † 1  11/6465 (0.17%)  12/6452 (0.19%) 
Pancreatitis chronic † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Pancreatitis relapsing † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Peptic ulcer † 1  2/6465 (0.03%)  1/6452 (0.02%) 
Peptic ulcer haemorrhage † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Peptic ulcer perforation † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Periproctitis † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Peritoneal adhesions † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Peritoneal mesothelial hyperplasia † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Pneumoperitoneum † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Proctitis † 1  1/6465 (0.02%)  1/6452 (0.02%) 
Radicular cyst † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Rectal fissure † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Rectal haemorrhage † 1  9/6465 (0.14%)  7/6452 (0.11%) 
Rectal polyp † 1  0/6465 (0.00%)  2/6452 (0.03%) 
Rectal ulcer haemorrhage † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Reflux gastritis † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Retroperitoneal haematoma † 1  1/6465 (0.02%)  5/6452 (0.08%) 
Retroperitoneal haemorrhage † 1  1/6465 (0.02%)  1/6452 (0.02%) 
Short-bowel syndrome † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Small intestinal obstruction † 1  7/6465 (0.11%)  0/6452 (0.00%) 
Small intestinal perforation † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Small intestine polyp † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Stomatitis † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Subileus † 1  2/6465 (0.03%)  2/6452 (0.03%) 
Umbilical hernia † 1  3/6465 (0.05%)  1/6452 (0.02%) 
Umbilical hernia, obstructive † 1  1/6465 (0.02%)  1/6452 (0.02%) 
Upper gastrointestinal haemorrhage † 1  8/6465 (0.12%)  10/6452 (0.15%) 
Uraemic gastropathy † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Varices oesophageal † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Vomiting † 1  6/6465 (0.09%)  4/6452 (0.06%) 
General disorders     
Asthenia † 1  4/6465 (0.06%)  6/6452 (0.09%) 
Cardiac death † 1  3/6465 (0.05%)  2/6452 (0.03%) 
Chest discomfort † 1  10/6465 (0.15%)  8/6452 (0.12%) 
Chest pain † 1  15/6465 (0.23%)  20/6452 (0.31%) 
Death † 1  36/6465 (0.56%)  34/6452 (0.53%) 
Device dislocation † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Device malfunction † 1  0/6465 (0.00%)  3/6452 (0.05%) 
Device occlusion † 1  14/6465 (0.22%)  27/6452 (0.42%) 
Drug withdrawal syndrome † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Face oedema † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Fatigue † 1  3/6465 (0.05%)  1/6452 (0.02%) 
Gait disturbance † 1  2/6465 (0.03%)  1/6452 (0.02%) 
General physical health deterioration † 1  2/6465 (0.03%)  1/6452 (0.02%) 
Hernia obstructive † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Hypothermia † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Impaired healing † 1  5/6465 (0.08%)  1/6452 (0.02%) 
Inflammation † 1  1/6465 (0.02%)  2/6452 (0.03%) 
Influenza like illness † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Local swelling † 1  2/6465 (0.03%)  0/6452 (0.00%) 
Malaise † 1  0/6465 (0.00%)  2/6452 (0.03%) 
Medical device complication † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Mucosal haemorrhage † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Multi-organ failure † 1  9/6465 (0.14%)  3/6452 (0.05%) 
Nodule † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Non-cardiac chest pain † 1  298/6465 (4.61%)  248/6452 (3.84%) 
Oedema peripheral † 1  6/6465 (0.09%)  3/6452 (0.05%) 
Pain † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Patient-device incompatibility † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Pelvic mass † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Polyserositis † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Pseudopolyp † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Puncture site haemorrhage † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Pyrexia † 1  11/6465 (0.17%)  9/6452 (0.14%) 
Stent malfunction † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Stent-graft endoleak † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Sudden cardiac death † 1  35/6465 (0.54%)  26/6452 (0.40%) 
Sudden death † 1  28/6465 (0.43%)  26/6452 (0.40%) 
Surgical failure † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Systemic inflammatory response syndrome † 1  1/6465 (0.02%)  2/6452 (0.03%) 
Thrombosis in device † 1  8/6465 (0.12%)  8/6452 (0.12%) 
Ulcer haemorrhage † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Vessel puncture site thrombosis † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Hepatobiliary disorders     
Acute hepatic failure † 1  0/6465 (0.00%)  2/6452 (0.03%) 
Alcoholic liver disease † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Autoimmune hepatitis † 1  2/6465 (0.03%)  0/6452 (0.00%) 
Bile duct obstruction † 1  2/6465 (0.03%)  0/6452 (0.00%) 
Bile duct stenosis † 1  0/6465 (0.00%)  2/6452 (0.03%) 
Bile duct stone † 1  3/6465 (0.05%)  4/6452 (0.06%) 
Biliary colic † 1  1/6465 (0.02%)  2/6452 (0.03%) 
Biliary dyskinesia † 1  2/6465 (0.03%)  0/6452 (0.00%) 
Cholangitis † 1  3/6465 (0.05%)  2/6452 (0.03%) 
Cholangitis acute † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Cholecystitis † 1  13/6465 (0.20%)  10/6452 (0.15%) 
Cholecystitis acute † 1  15/6465 (0.23%)  15/6452 (0.23%) 
Cholecystitis chronic † 1  3/6465 (0.05%)  0/6452 (0.00%) 
Cholelithiasis † 1  18/6465 (0.28%)  23/6452 (0.36%) 
Cholestasis † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Drug-induced liver injury † 1  3/6465 (0.05%)  7/6452 (0.11%) 
Hepatic cirrhosis † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Hepatic cyst † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Hepatic failure † 1  0/6465 (0.00%)  4/6452 (0.06%) 
Hepatic function abnormal † 1  5/6465 (0.08%)  2/6452 (0.03%) 
Hepatitis † 1  3/6465 (0.05%)  1/6452 (0.02%) 
Hepatitis acute † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Hepatitis alcoholic † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Hepatitis cholestatic † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Hepatitis toxic † 1  1/6465 (0.02%)  1/6452 (0.02%) 
Hepatocellular injury † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Hepatorenal syndrome † 1  2/6465 (0.03%)  0/6452 (0.00%) 
Hepatotoxicity † 1  2/6465 (0.03%)  0/6452 (0.00%) 
Hyperbilirubinaemia † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Ischaemic hepatitis † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Jaundice cholestatic † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Liver injury † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Immune system disorders     
Allergy to arthropod bite † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Anaphylactic reaction † 1  2/6465 (0.03%)  4/6452 (0.06%) 
Anaphylactic shock † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Drug hypersensitivity † 1  1/6465 (0.02%)  2/6452 (0.03%) 
Hypersensitivity † 1  4/6465 (0.06%)  2/6452 (0.03%) 
Sarcoidosis † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Infections and infestations     
Abdominal abscess † 1  1/6465 (0.02%)  1/6452 (0.02%) 
Abdominal infection † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Abscess † 1  2/6465 (0.03%)  1/6452 (0.02%) 
Abscess intestinal † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Abscess limb † 1  6/6465 (0.09%)  2/6452 (0.03%) 
Acarodermatitis † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Acute tonsillitis † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Anal abscess † 1  6/6465 (0.09%)  3/6452 (0.05%) 
Appendiceal abscess † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Appendicitis † 1  8/6465 (0.12%)  9/6452 (0.14%) 
Appendicitis perforated † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Arthritis bacterial † 1  1/6465 (0.02%)  3/6452 (0.05%) 
Arthritis infective † 1  2/6465 (0.03%)  0/6452 (0.00%) 
Bacteraemia † 1  2/6465 (0.03%)  0/6452 (0.00%) 
Bacterial prostatitis † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Bone abscess † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Bronchitis † 1  19/6465 (0.29%)  29/6452 (0.45%) 
Bronchopneumonia † 1  10/6465 (0.15%)  9/6452 (0.14%) 
Burkholderia pseudomallei infection † 1  0/6465 (0.00%)  2/6452 (0.03%) 
Bursitis infective † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Campylobacter infection † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Cellulitis † 1  24/6465 (0.37%)  27/6452 (0.42%) 
Cellulitis staphylococcal † 1  2/6465 (0.03%)  0/6452 (0.00%) 
Cholangitis suppurative † 1  1/6465 (0.02%)  1/6452 (0.02%) 
Cholecystitis infective † 1  2/6465 (0.03%)  1/6452 (0.02%) 
Chronic sinusitis † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Clostridium difficile colitis † 1  5/6465 (0.08%)  3/6452 (0.05%) 
Clostridium difficile infection † 1  7/6465 (0.11%)  2/6452 (0.03%) 
Creutzfeldt-Jakob disease † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Cystitis † 1  6/6465 (0.09%)  2/6452 (0.03%) 
Cytomegalovirus infection † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Device related infection † 1  2/6465 (0.03%)  1/6452 (0.02%) 
Device related sepsis † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Diabetic foot infection † 1  1/6465 (0.02%)  1/6452 (0.02%) 
Diabetic gangrene † 1  1/6465 (0.02%)  2/6452 (0.03%) 
Diarrhoea infectious † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Diverticulitis † 1  16/6465 (0.25%)  14/6452 (0.22%) 
Eczema infected † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Empyema † 1  2/6465 (0.03%)  0/6452 (0.00%) 
Endocarditis † 1  2/6465 (0.03%)  1/6452 (0.02%) 
Endocarditis enterococcal † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Enteritis infectious † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Enterocolitis infectious † 1  0/6465 (0.00%)  2/6452 (0.03%) 
Erysipelas † 1  4/6465 (0.06%)  6/6452 (0.09%) 
Escherichia urinary tract infection † 1  3/6465 (0.05%)  1/6452 (0.02%) 
Gallbladder abscess † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Gallbladder empyema † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Gangrene † 1  8/6465 (0.12%)  7/6452 (0.11%) 
Gastric infection † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Gastroenteritis † 1  20/6465 (0.31%)  18/6452 (0.28%) 
Gastroenteritis clostridial † 1  2/6465 (0.03%)  0/6452 (0.00%) 
Gastroenteritis norovirus † 1  2/6465 (0.03%)  0/6452 (0.00%) 
Gastroenteritis viral † 1  2/6465 (0.03%)  2/6452 (0.03%) 
Gastrointestinal infection † 1  1/6465 (0.02%)  1/6452 (0.02%) 
Graft infection † 1  1/6465 (0.02%)  1/6452 (0.02%) 
Groin abscess † 1  2/6465 (0.03%)  0/6452 (0.00%) 
Groin infection † 1  2/6465 (0.03%)  0/6452 (0.00%) 
Haematoma infection † 1  1/6465 (0.02%)  1/6452 (0.02%) 
Helicobacter infection † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Hepatitis C † 1  2/6465 (0.03%)  1/6452 (0.02%) 
Hepatitis E † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Hepatitis infectious mononucleosis † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Herpes zoster † 1  3/6465 (0.05%)  1/6452 (0.02%) 
Impetigo † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Infected dermal cyst † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Infected lymphocele † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Infected skin ulcer † 1  4/6465 (0.06%)  2/6452 (0.03%) 
Infection † 1  1/6465 (0.02%)  2/6452 (0.03%) 
Infective exacerbation of chronic obstructive airways disease † 1  2/6465 (0.03%)  1/6452 (0.02%) 
Influenza † 1  4/6465 (0.06%)  3/6452 (0.05%) 
Klebsiella infection † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Klebsiella sepsis † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Labyrinthitis † 1  2/6465 (0.03%)  2/6452 (0.03%) 
Liver abscess † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Lobar pneumonia † 1  4/6465 (0.06%)  4/6452 (0.06%) 
Localised infection † 1  1/6465 (0.02%)  1/6452 (0.02%) 
Lower respiratory tract infection † 1  2/6465 (0.03%)  4/6452 (0.06%) 
Lung abscess † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Lung infection † 1  2/6465 (0.03%)  3/6452 (0.05%) 
Lymphangitis † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Malaria † 1  1/6465 (0.02%)  1/6452 (0.02%) 
Mastoiditis † 1  0/6465 (0.00%)  2/6452 (0.03%) 
Mediastinitis † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Meningitis tuberculous † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Necrotising fasciitis † 1  0/6465 (0.00%)  2/6452 (0.03%) 
Neuroborreliosis † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Oesophageal candidiasis † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Orchitis † 1  1/6465 (0.02%)  2/6452 (0.03%) 
Osteomyelitis † 1  2/6465 (0.03%)  7/6452 (0.11%) 
Osteomyelitis acute † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Osteomyelitis chronic † 1  1/6465 (0.02%)  2/6452 (0.03%) 
Otitis media † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Pelvic abscess † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Pericarditis tuberculous † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Peritoneal abscess † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Peritonitis † 1  2/6465 (0.03%)  0/6452 (0.00%) 
Peritonsillar abscess † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Pharyngitis † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Pneumococcal sepsis † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Pneumonia † 1  113/6465 (1.75%)  130/6452 (2.01%) 
Pneumonia bacterial † 1  2/6465 (0.03%)  1/6452 (0.02%) 
Pneumonia fungal † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Pneumonia influenzal † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Pneumonia pseudomonas aeruginosa † 1  0/6465 (0.00%)  2/6452 (0.03%) 
Pneumonia staphylococcal † 1  1/6465 (0.02%)  1/6452 (0.02%) 
Pneumonia streptococcal † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Pneumonia viral † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Post procedural infection † 1  0/6465 (0.00%)  3/6452 (0.05%) 
Post procedural pneumonia † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Post procedural sepsis † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Postoperative abscess † 1  2/6465 (0.03%)  0/6452 (0.00%) 
Postoperative wound infection † 1  4/6465 (0.06%)  6/6452 (0.09%) 
Pseudomembranous colitis † 1  2/6465 (0.03%)  1/6452 (0.02%) 
Pseudomonas infection † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Pulmonary sepsis † 1  1/6465 (0.02%)  2/6452 (0.03%) 
Pulmonary tuberculosis † 1  1/6465 (0.02%)  1/6452 (0.02%) 
Pyelonephritis † 1  5/6465 (0.08%)  3/6452 (0.05%) 
Pyelonephritis acute † 1  4/6465 (0.06%)  1/6452 (0.02%) 
Pyoderma streptococcal † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Renal abscess † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Respiratory tract infection † 1  5/6465 (0.08%)  5/6452 (0.08%) 
Respiratory tract infection viral † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Respiratory tract infection bacterial † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Salmonellosis † 1  2/6465 (0.03%)  0/6452 (0.00%) 
Scrotal abscess † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Sepsis † 1  23/6465 (0.36%)  24/6452 (0.37%) 
Septic shock † 1  9/6465 (0.14%)  6/6452 (0.09%) 
Sinusitis † 1  2/6465 (0.03%)  3/6452 (0.05%) 
Skin bacterial infection † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Skin infection † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Staphylococcal abscess † 1  0/6465 (0.00%)  2/6452 (0.03%) 
Staphylococcal bacteraemia † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Staphylococcal infection † 1  1/6465 (0.02%)  3/6452 (0.05%) 
Staphylococcal sepsis † 1  3/6465 (0.05%)  1/6452 (0.02%) 
Staphylococcal skin infection † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Streptococcal bacteraemia † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Streptococcal sepsis † 1  0/6465 (0.00%)  2/6452 (0.03%) 
Subcutaneous abscess † 1  1/6465 (0.02%)  1/6452 (0.02%) 
Superinfection † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Testicular abscess † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Tonsillitis † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Tracheitis † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Tracheobronchitis † 1  1/6465 (0.02%)  1/6452 (0.02%) 
Upper respiratory tract infection † 1  6/6465 (0.09%)  5/6452 (0.08%) 
Upper respiratory tract infection bacterial † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Urinary tract infection † 1  47/6465 (0.73%)  25/6452 (0.39%) 
Urinary tract infection bacterial † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Urinary tract infection enterococcal † 1  2/6465 (0.03%)  0/6452 (0.00%) 
Urinary tract infection pseudomonal † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Urosepsis † 1  6/6465 (0.09%)  7/6452 (0.11%) 
Vestibular neuronitis † 1  2/6465 (0.03%)  1/6452 (0.02%) 
Viral infection † 1  4/6465 (0.06%)  1/6452 (0.02%) 
Viral upper respiratory tract infection † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Wound infection † 1  5/6465 (0.08%)  5/6452 (0.08%) 
Wound infection pseudomonas † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Wound infection staphylococcal † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Wound sepsis † 1  0/6465 (0.00%)  2/6452 (0.03%) 
Pneumonia legionella † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Injury, poisoning and procedural complications     
Accidental overdose † 1  3/6465 (0.05%)  2/6452 (0.03%) 
Afferent loop syndrome † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Alcohol poisoning † 1  0/6465 (0.00%)  5/6452 (0.08%) 
Anaemia postoperative † 1  1/6465 (0.02%)  3/6452 (0.05%) 
Anastomotic ulcer † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Ankle fracture † 1  4/6465 (0.06%)  6/6452 (0.09%) 
Arterial restenosis † 1  2/6465 (0.03%)  1/6452 (0.02%) 
Arthropod sting † 1  2/6465 (0.03%)  0/6452 (0.00%) 
Brain contusion † 1  4/6465 (0.06%)  0/6452 (0.00%) 
Burns second degree † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Burns third degree † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Cardiac function disturbance postoperative † 1  1/6465 (0.02%)  1/6452 (0.02%) 
Cardiac procedure complication † 1  2/6465 (0.03%)  1/6452 (0.02%) 
Carotid artery restenosis † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Cerebral hyperperfusion syndrome † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Cervical vertebral fracture † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Chest injury † 1  1/6465 (0.02%)  1/6452 (0.02%) 
Clavicle fracture † 1  3/6465 (0.05%)  1/6452 (0.02%) 
Comminuted fracture † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Compression fracture † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Concussion † 1  2/6465 (0.03%)  1/6452 (0.02%) 
Contrast media reaction † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Contusion † 1  5/6465 (0.08%)  5/6452 (0.08%) 
Coronary artery reocclusion † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Coronary artery restenosis † 1  30/6465 (0.46%)  30/6452 (0.46%) 
Craniocerebral injury † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Cystitis radiation † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Dural tear † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Electric shock † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Excoriation † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Exposure via inhalation † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Eye penetration † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Facial bones fracture † 1  3/6465 (0.05%)  1/6452 (0.02%) 
Fall † 1  6/6465 (0.09%)  3/6452 (0.05%) 
Fat embolism † 1  0/6465 (0.00%)  2/6452 (0.03%) 
Femoral neck fracture † 1  4/6465 (0.06%)  6/6452 (0.09%) 
Femur fracture † 1  10/6465 (0.15%)  7/6452 (0.11%) 
Fibula fracture † 1  2/6465 (0.03%)  1/6452 (0.02%) 
Foot fracture † 1  0/6465 (0.00%)  3/6452 (0.05%) 
Foreign body † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Fractured ischium † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Gastrointestinal disorder postoperative † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Gastrointestinal injury † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Graft thrombosis † 1  0/6465 (0.00%)  2/6452 (0.03%) 
Gun shot wound † 1  0/6465 (0.00%)  2/6452 (0.03%) 
Hand fracture † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Head injury † 1  4/6465 (0.06%)  2/6452 (0.03%) 
Heart injury † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Heat exhaustion † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Heat stroke † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Hip fracture † 1  10/6465 (0.15%)  11/6452 (0.17%) 
Humerus fracture † 1  5/6465 (0.08%)  3/6452 (0.05%) 
Incision site pain † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Incisional hernia † 1  1/6465 (0.02%)  1/6452 (0.02%) 
Injury † 1  0/6465 (0.00%)  2/6452 (0.03%) 
Intentional overdose † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Intestinal anastomosis complication † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Jaw fracture † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Joint dislocation † 1  0/6465 (0.00%)  5/6452 (0.08%) 
Joint injury † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Kidney contusion † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Laceration † 1  2/6465 (0.03%)  2/6452 (0.03%) 
Ligament rupture † 1  2/6465 (0.03%)  1/6452 (0.02%) 
Ligament sprain † 1  1/6465 (0.02%)  2/6452 (0.03%) 
Limb injury † 1  4/6465 (0.06%)  1/6452 (0.02%) 
Lower limb fracture † 1  1/6465 (0.02%)  2/6452 (0.03%) 
Lumbar vertebral fracture † 1  3/6465 (0.05%)  4/6452 (0.06%) 
Meniscus injury † 1  1/6465 (0.02%)  4/6452 (0.06%) 
Mountain sickness acute † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Multiple fractures † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Multiple injuries † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Muscle rupture † 1  3/6465 (0.05%)  0/6452 (0.00%) 
Muscle strain † 1  1/6465 (0.02%)  1/6452 (0.02%) 
Overdose † 1  4/6465 (0.06%)  4/6452 (0.06%) 
Pelvic fracture † 1  3/6465 (0.05%)  1/6452 (0.02%) 
Peroneal nerve injury † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Pneumoconiosis † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Post procedural complication † 1  4/6465 (0.06%)  2/6452 (0.03%) 
Post procedural contusion † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Post procedural fistula † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Post procedural haemorrhage † 1  2/6465 (0.03%)  1/6452 (0.02%) 
Post procedural myocardial infarction † 1  6/6465 (0.09%)  3/6452 (0.05%) 
Post-traumatic pain † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Postoperative ileus † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Postoperative wound complication † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Postpericardiotomy syndrome † 1  1/6465 (0.02%)  2/6452 (0.03%) 
Procedural complication † 1  1/6465 (0.02%)  1/6452 (0.02%) 
Procedural haemorrhage † 1  1/6465 (0.02%)  1/6452 (0.02%) 
Procedural headache † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Procedural pain † 1  2/6465 (0.03%)  0/6452 (0.00%) 
Pseudomeningocele † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Pubis fracture † 1  3/6465 (0.05%)  1/6452 (0.02%) 
Pulmonary contusion † 1  2/6465 (0.03%)  1/6452 (0.02%) 
Radius fracture † 1  2/6465 (0.03%)  4/6452 (0.06%) 
Renal haematoma † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Rib fracture † 1  9/6465 (0.14%)  7/6452 (0.11%) 
Road traffic accident † 1  5/6465 (0.08%)  3/6452 (0.05%) 
Scapula fracture † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Scrotal haematoma † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Seroma † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Shunt stenosis † 1  2/6465 (0.03%)  0/6452 (0.00%) 
Shunt thrombosis † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Skull fracture † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Skull fractured base † 1  1/6465 (0.02%)  1/6452 (0.02%) 
Spinal column injury † 1  0/6465 (0.00%)  2/6452 (0.03%) 
Spinal compression fracture † 1  2/6465 (0.03%)  0/6452 (0.00%) 
Spinal fracture † 1  1/6465 (0.02%)  3/6452 (0.05%) 
Splenic injury † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Sternal fracture † 1  2/6465 (0.03%)  0/6452 (0.00%) 
Subcutaneous haematoma † 1  1/6465 (0.02%)  1/6452 (0.02%) 
Subdural haematoma † 1  6/6465 (0.09%)  5/6452 (0.08%) 
Subdural haemorrhage † 1  1/6465 (0.02%)  2/6452 (0.03%) 
Tendon injury † 1  0/6465 (0.00%)  2/6452 (0.03%) 
Tendon rupture † 1  1/6465 (0.02%)  4/6452 (0.06%) 
Thoracic vertebral fracture † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Tibia fracture † 1  3/6465 (0.05%)  1/6452 (0.02%) 
Toxicity to various agents † 1  4/6465 (0.06%)  5/6452 (0.08%) 
Traumatic intracranial haemorrhage † 1  0/6465 (0.00%)  2/6452 (0.03%) 
Traumatic shock † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Traumatic ulcer † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Upper limb fracture † 1  1/6465 (0.02%)  1/6452 (0.02%) 
Vascular graft complication † 1  1/6465 (0.02%)  2/6452 (0.03%) 
Vascular graft occlusion † 1  3/6465 (0.05%)  0/6452 (0.00%) 
Vascular graft thrombosis0 † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Vascular procedure complication † 1  0/6465 (0.00%)  2/6452 (0.03%) 
Vascular pseudoaneurysm † 1  8/6465 (0.12%)  2/6452 (0.03%) 
Wound † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Wound dehiscence † 1  2/6465 (0.03%)  1/6452 (0.02%) 
Wound necrosis † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Wrist fracture † 1  1/6465 (0.02%)  1/6452 (0.02%) 
Investigations     
Alanine aminotransferase increased † 1  4/6465 (0.06%)  6/6452 (0.09%) 
Ammonia increased † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Aspartate aminotransferase increased † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Blood bilirubin increased † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Blood creatinine increased † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Blood glucose increased † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Blood potassium decreased † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Blood potassium increased † 1  1/6465 (0.02%)  1/6452 (0.02%) 
C-reactive protein increased † 1  1/6465 (0.02%)  2/6452 (0.03%) 
Cardiac enzymes increased † 1  1/6465 (0.02%)  1/6452 (0.02%) 
Cardiac output decreased † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Cardiac stress test abnormal † 1  1/6465 (0.02%)  2/6452 (0.03%) 
Clostridium test positive † 1  1/6465 (0.02%)  0/6452 (0.00%) 
ECG signs of myocardial ischaemia † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Ejection fraction decreased † 1  1/6465 (0.02%)  2/6452 (0.03%) 
Electrocardiogram QT prolonged † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Electrocardiogram ST segment depression † 1  0/6465 (0.00%)  2/6452 (0.03%) 
Electrocardiogram ST segment elevation † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Exercise test abnormal † 1  3/6465 (0.05%)  0/6452 (0.00%) 
Fibrin D dimer increased † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Haemoglobin decreased † 1  1/6465 (0.02%)  1/6452 (0.02%) 
Heart rate increased † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Hepatic enzyme abnormal † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Hepatic enzyme increased † 1  8/6465 (0.12%)  9/6452 (0.14%) 
International normalised ratio increased † 1  0/6465 (0.00%)  2/6452 (0.03%) 
Laboratory test abnormal † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Liver function test abnormal † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Platelet count increased † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Pulmonary function test decreased † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Transaminases increased † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Troponin I increased † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Troponin T increased † 1  1/6465 (0.02%)  3/6452 (0.05%) 
Troponin increased † 1  16/6465 (0.25%)  7/6452 (0.11%) 
Weight decreased † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Metabolism and nutrition disorders     
Decreased appetite † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Dehydration † 1  18/6465 (0.28%)  19/6452 (0.29%) 
Diabetes mellitus inadequate control † 1  19/6465 (0.29%)  17/6452 (0.26%) 
Diabetic ketoacidosis † 1  3/6465 (0.05%)  4/6452 (0.06%) 
Electrolyte imbalance † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Failure to thrive † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Fluid retention † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Gout † 1  3/6465 (0.05%)  1/6452 (0.02%) 
Hydraemia † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Hypercalcaemia † 1  0/6465 (0.00%)  3/6452 (0.05%) 
Hyperglycaemia † 1  5/6465 (0.08%)  5/6452 (0.08%) 
Hyperkalaemia † 1  4/6465 (0.06%)  6/6452 (0.09%) 
Hyperlipidaemia † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Hypoglycaemia † 1  11/6465 (0.17%)  13/6452 (0.20%) 
Hypokalaemia † 1  7/6465 (0.11%)  5/6452 (0.08%) 
Hypomagnesaemia † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Hyponatraemia † 1  10/6465 (0.15%)  6/6452 (0.09%) 
Hypophagia † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Hypovolaemia † 1  2/6465 (0.03%)  3/6452 (0.05%) 
Insulin-requiring type 2 diabetes mellitus † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Malnutrition † 1  2/6465 (0.03%)  2/6452 (0.03%) 
Metabolic acidosis † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Type 2 diabetes mellitus † 1  21/6465 (0.32%)  21/6452 (0.33%) 
Abdominal wall abscess † 1  3/6465 (0.05%)  0/6452 (0.00%) 
Musculoskeletal and connective tissue disorders     
Ankylosing spondylitis † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Arthralgia † 1  2/6465 (0.03%)  2/6452 (0.03%) 
Arthritis † 1  6/6465 (0.09%)  7/6452 (0.11%) 
Arthropathy † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Back pain † 1  10/6465 (0.15%)  8/6452 (0.12%) 
Bursitis † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Cervical spinal stenosis † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Compartment syndrome † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Costochondritis † 1  2/6465 (0.03%)  1/6452 (0.02%) 
Fistula † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Flank pain † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Foot deformity † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Fracture malunion † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Fracture nonunion † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Gouty arthritis † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Intervertebral disc degeneration † 1  2/6465 (0.03%)  1/6452 (0.02%) 
Intervertebral disc disorder † 1  2/6465 (0.03%)  0/6452 (0.00%) 
Intervertebral disc protrusion † 1  11/6465 (0.17%)  9/6452 (0.14%) 
Joint instability † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Limb discomfort † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Lumbar spinal stenosis † 1  1/6465 (0.02%)  4/6452 (0.06%) 
Muscle disorder † 1  1/6465 (0.02%)  1/6452 (0.02%) 
Muscle haemorrhage † 1  1/6465 (0.02%)  1/6452 (0.02%) 
Muscle spasms † 1  2/6465 (0.03%)  0/6452 (0.00%) 
Muscular weakness † 1  1/6465 (0.02%)  2/6452 (0.03%) 
Musculoskeletal chest pain † 1  21/6465 (0.32%)  9/6452 (0.14%) 
Musculoskeletal pain † 1  6/6465 (0.09%)  4/6452 (0.06%) 
Myalgia † 1  3/6465 (0.05%)  3/6452 (0.05%) 
Myositis † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Neck pain † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Osteoarthritis † 1  40/6465 (0.62%)  29/6452 (0.45%) 
Osteochondritis † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Osteochondrosis † 1  1/6465 (0.02%)  1/6452 (0.02%) 
Osteonecrosis † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Osteoporosis † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Pain in extremity † 1  3/6465 (0.05%)  6/6452 (0.09%) 
Pain in jaw † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Plantar fascial fibromatosis † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Polyarthritis † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Polymyalgia rheumatica † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Polymyositis † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Psoriatic arthropathy † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Rhabdomyolysis † 1  3/6465 (0.05%)  7/6452 (0.11%) 
Rheumatoid arthritis † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Rotator cuff syndrome † 1  2/6465 (0.03%)  2/6452 (0.03%) 
Sensation of heaviness † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Sjogren's syndrome † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Spinal column stenosis † 1  2/6465 (0.03%)  6/6452 (0.09%) 
Spinal osteoarthritis † 1  1/6465 (0.02%)  9/6452 (0.14%) 
Spinal pain † 1  2/6465 (0.03%)  4/6452 (0.06%) 
Spondyloarthropathy † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Spondylolisthesis † 1  3/6465 (0.05%)  1/6452 (0.02%) 
Spondylolysis † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Sympathetic posterior cervical syndrome † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Synovial cyst † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Synovitis † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Tendonitis † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Acute leukaemia † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Acute myeloid leukaemia † 1  2/6465 (0.03%)  1/6452 (0.02%) 
Acute promyelocytic leukaemia † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Adenocarcinoma † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Adenocarcinoma gastric † 1  1/6465 (0.02%)  1/6452 (0.02%) 
Adenocarcinoma of colon † 1  7/6465 (0.11%)  0/6452 (0.00%) 
Adenocarcinoma pancreas † 1  1/6465 (0.02%)  1/6452 (0.02%) 
Adenoma benign † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Adenosquamous cell lung cancer † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Anal cancer † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Angiocentric lymphoma † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Angiosarcoma metastatic † 1  0/6465 (0.00%)  1/6452 (0.02%) 
B-cell lymphoma † 1  0/6465 (0.00%)  1/6452 (0.02%) 
B-cell lymphoma recurrent † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Basal cell carcinoma † 1  4/6465 (0.06%)  2/6452 (0.03%) 
Benign anorectal neoplasm † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Benign breast neoplasm † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Benign gastric neoplasm † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Benign gastrointestinal neoplasm † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Benign laryngeal neoplasm † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Benign lung neoplasm † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Benign neoplasm † 1  1/6465 (0.02%)  1/6452 (0.02%) 
Benign neoplasm of adrenal gland † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Benign neoplasm of bladder † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Benign neoplasm of prostate † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Bile duct cancer † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Bladder cancer † 1  15/6465 (0.23%)  10/6452 (0.15%) 
Bladder cancer recurrent † 1  5/6465 (0.08%)  2/6452 (0.03%) 
Bladder cancer stage 0, with cancer in situ † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Bladder neoplasm † 1  4/6465 (0.06%)  1/6452 (0.02%) 
Bladder papilloma † 1  1/6465 (0.02%)  1/6452 (0.02%) 
Bladder transitional cell carcinoma † 1  1/6465 (0.02%)  1/6452 (0.02%) 
Bone giant cell tumour benign † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Borderline ovarian tumour † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Brain neoplasm malignant † 1  1/6465 (0.02%)  1/6452 (0.02%) 
Breast cancer † 1  8/6465 (0.12%)  10/6452 (0.15%) 
Breast cancer metastatic † 1  1/6465 (0.02%)  5/6452 (0.08%) 
Bronchial carcinoma † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Central nervous system neoplasm † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Cerebellar tumour † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Cervix carcinoma † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Cholangiocarcinoma † 1  1/6465 (0.02%)  1/6452 (0.02%) 
Choroid melanoma † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Chronic lymphocytic leukaemia † 1  0/6465 (0.00%)  2/6452 (0.03%) 
Chronic myeloid leukaemia † 1  1/6465 (0.02%)  3/6452 (0.05%) 
Clear cell renal cell carcinoma † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Colon adenoma † 1  4/6465 (0.06%)  2/6452 (0.03%) 
Colon cancer † 1  9/6465 (0.14%)  12/6452 (0.19%) 
Colon cancer metastatic † 1  1/6465 (0.02%)  2/6452 (0.03%) 
Colorectal adenocarcinoma † 1  1/6465 (0.02%)  1/6452 (0.02%) 
Cystadenocarcinoma ovary † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Desmoplastic melanoma † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Diffuse large B-cell lymphoma † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Endometrial cancer † 1  1/6465 (0.02%)  1/6452 (0.02%) 
Essential thrombocythaemia † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Fibroma † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Gastric cancer † 1  6/6465 (0.09%)  6/6452 (0.09%) 
Gastric cancer stage I † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Gastric neoplasm † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Gastrointestinal cancer metastatic † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Gastrointestinal carcinoma † 1  1/6465 (0.02%)  2/6452 (0.03%) 
Gastrointestinal stromal cancer † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Gastrointestinal stromal tumour † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Gastrointestinal tract adenoma † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Glioblastoma multiforme † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Glottis carcinoma † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Haemangioma † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Haemangioma of liver † 1  2/6465 (0.03%)  0/6452 (0.00%) 
Hepatic cancer metastatic † 1  2/6465 (0.03%)  1/6452 (0.02%) 
Hepatocellular carcinoma † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Invasive ductal breast carcinoma † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Large cell lung cancer stage IV † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Large intestine benign neoplasm † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Laryngeal cancer † 1  1/6465 (0.02%)  3/6452 (0.05%) 
Laryngeal squamous cell carcinoma † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Leiomyosarcoma metastatic † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Leukaemia † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Lip neoplasm malignant stage unspecified † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Lip squamous cell carcinoma † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Lipoma † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Lung adenocarcinoma † 1  1/6465 (0.02%)  2/6452 (0.03%) 
Lung cancer metastatic † 1  9/6465 (0.14%)  12/6452 (0.19%) 
Lung carcinoma cell type unspecified recurrent † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Lung neoplasm † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Lung neoplasm malignant † 1  14/6465 (0.22%)  11/6452 (0.17%) 
Lung squamous cell carcinoma metastatic † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Lung squamous cell carcinoma stage I † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Lymphoma † 1  4/6465 (0.06%)  1/6452 (0.02%) 
Malignant melanoma † 1  6/6465 (0.09%)  9/6452 (0.14%) 
Malignant neoplasm of ampulla of Vater † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Malignant neoplasm of unknown primary site † 1  1/6465 (0.02%)  1/6452 (0.02%) 
Malignant neoplasm progression † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Melanoma recurrent † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Meningioma † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Meningioma benign † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Mesothelioma malignant † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Metastases to bone † 1  3/6465 (0.05%)  3/6452 (0.05%) 
Metastases to central nervous system † 1  2/6465 (0.03%)  2/6452 (0.03%) 
Metastases to liver † 1  7/6465 (0.11%)  3/6452 (0.05%) 
Metastases to lung † 1  1/6465 (0.02%)  2/6452 (0.03%) 
Metastases to lymph nodes † 1  3/6465 (0.05%)  1/6452 (0.02%) 
Metastases to peritoneum † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Metastases to pleura † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Metastases to spine † 1  0/6465 (0.00%)  3/6452 (0.05%) 
Metastatic bronchial carcinoma † 1  1/6465 (0.02%)  1/6452 (0.02%) 
Metastatic gastric cancer † 1  2/6465 (0.03%)  1/6452 (0.02%) 
Metastatic lymphoma † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Metastatic malignant melanoma † 1  3/6465 (0.05%)  1/6452 (0.02%) 
Metastatic neoplasm † 1  0/6465 (0.00%)  3/6452 (0.05%) 
Metastatic renal cell carcinoma † 1  0/6465 (0.00%)  2/6452 (0.03%) 
Metastatic squamous cell carcinoma † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Metastatic uterine cancer † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Myelodysplastic syndrome † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Myeloproliferative disorder † 1  0/6465 (0.00%)  2/6452 (0.03%) 
Neoplasm † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Neoplasm malignant † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Neurilemmoma benign † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Neuroendocrine carcinoma † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Neuroendocrine carcinoma of the skin † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Neuroendocrine tumour † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Non-small cell lung cancer † 1  2/6465 (0.03%)  2/6452 (0.03%) 
Non-small cell lung cancer stage IIIB † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Non-small cell lung cancer metastatic † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Non-small cell lung cancer recurrent † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Oesophageal adenocarcinoma † 1  3/6465 (0.05%)  0/6452 (0.00%) 
Oesophageal cancer metastatic † 1  1/6465 (0.02%)  1/6452 (0.02%) 
Oesophageal carcinoma † 1  4/6465 (0.06%)  2/6452 (0.03%) 
Oral cavity cancer metastatic † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Oropharyngeal cancer † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Osteosarcoma † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Ovarian cancer † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Ovarian cancer metastatic † 1  2/6465 (0.03%)  0/6452 (0.00%) 
Ovarian germ cell teratoma benign † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Pancreatic carcinoma † 1  1/6465 (0.02%)  2/6452 (0.03%) 
Pancreatic carcinoma metastatic † 1  3/6465 (0.05%)  1/6452 (0.02%) 
Paraneoplastic syndrome † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Paraproteinaemia † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Plasma cell myeloma † 1  1/6465 (0.02%)  2/6452 (0.03%) 
Plasmacytoma † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Pleomorphic adenoma † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Polycythaemia vera † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Precursor B-lymphoblastic lymphoma † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Prostate cancer † 1  21/6465 (0.32%)  25/6452 (0.39%) 
Prostate cancer metastatic † 1  2/6465 (0.03%)  7/6452 (0.11%) 
Prostate cancer recurrent † 1  1/6465 (0.02%)  1/6452 (0.02%) 
Prostatic adenoma † 1  1/6465 (0.02%)  1/6452 (0.02%) 
Rectal adenocarcinoma † 1  1/6465 (0.02%)  1/6452 (0.02%) 
Rectal cancer † 1  3/6465 (0.05%)  4/6452 (0.06%) 
Rectal cancer metastatic † 1  1/6465 (0.02%)  4/6452 (0.06%) 
Rectosigmoid cancer † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Renal cancer † 1  6/6465 (0.09%)  9/6452 (0.14%) 
Renal cancer metastatic † 1  1/6465 (0.02%)  5/6452 (0.08%) 
Renal cell carcinoma † 1  1/6465 (0.02%)  2/6452 (0.03%) 
Renal cell carcinoma stage II † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Renal oncocytoma † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Sarcoma metastatic † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Signet-ring cell carcinoma † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Skin cancer † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Small cell lung cancer † 1  1/6465 (0.02%)  3/6452 (0.05%) 
Small cell lung cancer metastatic † 1  3/6465 (0.05%)  0/6452 (0.00%) 
Small intestine adenocarcinoma † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Squamous cell carcinoma † 1  1/6465 (0.02%)  2/6452 (0.03%) 
Squamous cell carcinoma of lung † 1  3/6465 (0.05%)  3/6452 (0.05%) 
Squamous cell carcinoma of skin † 1  1/6465 (0.02%)  1/6452 (0.02%) 
Squamous cell carcinoma of the tongue † 1  1/6465 (0.02%)  0/6452 (0.00%) 
T-cell lymphoma † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Testis cancer † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Thymoma † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Thyroid cancer † 1  1/6465 (0.02%)  1/6452 (0.02%) 
Thyroid cancer metastatic † 1  2/6465 (0.03%)  0/6452 (0.00%) 
Tongue cancer metastatic † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Tongue carcinoma stage IV † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Tongue neoplasm malignant stage unspecified † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Tonsil cancer metastatic † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Tracheal neoplasm † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Transitional cell carcinoma † 1  3/6465 (0.05%)  4/6452 (0.06%) 
Transitional cell carcinoma metastatic † 1  2/6465 (0.03%)  0/6452 (0.00%) 
Uterine cancer † 1  0/6465 (0.00%)  2/6452 (0.03%) 
Uterine leiomyoma † 1  2/6465 (0.03%)  2/6452 (0.03%) 
Vaginal cancer † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Allergy to arthropod sting † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Nervous system disorders     
Aphasia † 1  2/6465 (0.03%)  1/6452 (0.02%) 
Ataxia † 1  0/6465 (0.00%)  2/6452 (0.03%) 
Basilar migraine † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Brain injury † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Brain oedema † 1  2/6465 (0.03%)  1/6452 (0.02%) 
Brain stem stroke † 1  0/6465 (0.00%)  3/6452 (0.05%) 
Carotid arteriosclerosis † 1  3/6465 (0.05%)  3/6452 (0.05%) 
Carotid artery disease † 1  1/6465 (0.02%)  5/6452 (0.08%) 
Carotid artery occlusion † 1  2/6465 (0.03%)  0/6452 (0.00%) 
Carotid artery stenosis † 1  34/6465 (0.53%)  27/6452 (0.42%) 
Carotid sinus syndrome † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Carpal tunnel syndrome † 1  3/6465 (0.05%)  0/6452 (0.00%) 
Cerebellar ataxia † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Cerebellar infarction † 1  1/6465 (0.02%)  1/6452 (0.02%) 
Cerebral arteriosclerosis † 1  2/6465 (0.03%)  0/6452 (0.00%) 
Cerebral artery embolism † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Cerebral circulatory failure † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Cerebral haemorrhage † 1  2/6465 (0.03%)  7/6452 (0.11%) 
Cerebral infarction † 1  6/6465 (0.09%)  3/6452 (0.05%) 
Cerebral ischaemia † 1  3/6465 (0.05%)  4/6452 (0.06%) 
Cerebrovascular accident † 1  16/6465 (0.25%)  19/6452 (0.29%) 
Cerebrovascular disorder † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Cerebrovascular insufficiency † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Cervical myelopathy † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Cervical neuritis † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Cervical radiculopathy † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Cervicobrachial syndrome † 1  2/6465 (0.03%)  2/6452 (0.03%) 
Cognitive disorder † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Coma † 1  3/6465 (0.05%)  1/6452 (0.02%) 
Complex regional pain syndrome † 1  0/6465 (0.00%)  3/6452 (0.05%) 
Convulsion † 1  8/6465 (0.12%)  6/6452 (0.09%) 
Dementia † 1  1/6465 (0.02%)  1/6452 (0.02%) 
Dementia Alzheimer's type † 1  0/6465 (0.00%)  2/6452 (0.03%) 
Diabetic neuropathy † 1  1/6465 (0.02%)  1/6452 (0.02%) 
Dizziness † 1  7/6465 (0.11%)  13/6452 (0.20%) 
Dysaesthesia † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Dysarthria † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Embolic stroke † 1  4/6465 (0.06%)  4/6452 (0.06%) 
Encephalopathy † 1  0/6465 (0.00%)  2/6452 (0.03%) 
Epilepsy † 1  3/6465 (0.05%)  4/6452 (0.06%) 
Frontotemporal dementia † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Grand mal convulsion † 1  0/6465 (0.00%)  2/6452 (0.03%) 
Haemorrhage intracranial † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Haemorrhagic cerebral infarction † 1  1/6465 (0.02%)  2/6452 (0.03%) 
Haemorrhagic stroke † 1  10/6465 (0.15%)  6/6452 (0.09%) 
Haemorrhagic transformation stroke † 1  3/6465 (0.05%)  1/6452 (0.02%) 
Head discomfort † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Headache † 1  4/6465 (0.06%)  4/6452 (0.06%) 
Hemiparesis † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Hemiplegia † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Hemiplegic migraine † 1  1/6465 (0.02%)  1/6452 (0.02%) 
Hyperaesthesia † 1  1/6465 (0.02%)  0/6452 (0.00%) 
Hypoaesthesia † 1  5/6465 (0.08%)  3/6452 (0.05%) 
Hypoglycaemic coma † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Hypoglycaemic seizure † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Hypotonia † 1  0/6465 (0.00%)  1/6452 (0.02%) 
Hypoxic-ischaemic encephalopathy