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A Study to Assess the Efficacy and Safety of Enteric-Coated Acetylsalicylic Acid in Patients at Moderate Risk of Cardiovascular Disease (ARRIVE)

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: NCT00501059
Recruitment Status : Completed
First Posted : July 13, 2007
Results First Posted : January 8, 2018
Last Update Posted : October 26, 2018
Sponsor:
Information provided by (Responsible Party):
Bayer

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Investigator, Outcomes Assessor);   Primary Purpose: Prevention
Condition Moderate Risk of CVD
Interventions Drug: Aspirin (Acetylsalicylic acid, BAYE4465)
Drug: Placebo
Enrollment 12546
Recruitment Details Overall, 15823 subjects were screened. Of these, 3277 subjects were screening failures. The remaining 12546 subjects were randomized to treatment.
Pre-assignment Details  
Arm/Group Title Acetylsalicylic Acid (Aspirin, BAYE4465) Placebo
Hide Arm/Group Description Subjects received 1 tablet of enteric-coated acetylsalicylic acid [100 milligram (mg)] orally once daily. Subjects received 1 tablets of matching placebo orally once daily.
Period Title: Overall Study
Started 6270 6276
Completed 4402 4384
Not Completed 1868 1892
Reason Not Completed
Protocol Violation             80             69
Death             140             137
Other             236             239
Missing end-of-study page             91             92
Clinical endpoint reached             110             123
Insufficient therapeutic effect             4             5
Consent withdrawn by subject             817             873
Non-compliant with study treatment             23             16
Reason not given             3             1
Adverse Event             129             122
Lost to Follow-up             210             198
Not treated             25             17
Arm/Group Title Acetylsalicylic Acid (Aspirin, BAYE4465) Placebo Total
Hide Arm/Group Description Subjects received 1 tablet of enteric-coated acetylsalicylic acid [100 milligram (mg)] orally once daily. Subjects received 1 tablets of matching placebo orally once daily. Total of all reporting groups
Overall Number of Baseline Participants 6270 6276 12546
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 6270 participants 6276 participants 12546 participants
63.9  (7.10) 63.9  (7.05) 63.9  (7.08)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6270 participants 6276 participants 12546 participants
Female
1851
  29.5%
1857
  29.6%
3708
  29.6%
Male
4419
  70.5%
4419
  70.4%
8838
  70.4%
1.Primary Outcome
Title Time to the First Occurrence of the Composite Outcome of MI (Myocardial Infarction), Stroke, Cardiovascular Death, UA (Unstable Angina) or TIA (Transient Ischemic Attack)
Hide Description The primary efficacy endpoint was a composite outcome consisting of the first occurrence of confirmed MI, stroke, cardiovascular death, UA, TIA. The time to event was defined as the number of days from the date of randomization to the date of the event confirmed by adjudication. The numbers of days for milestones when 1%, 2%, 3% and 4% of the subjects have reached endpoint events were estimated from Kaplan-Meier-Analyses.
Time Frame Until follow-up (approximate 6 years)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intention-to-treat. The intent-to-treat (ITT) group (N=12546) consists of all patients who were randomized to the assigned study drug.
Arm/Group Title Acetylsalicylic Acid (Aspirin, BAYE4465) Placebo
Hide Arm/Group Description:
Subjects received 1 tablet of enteric-coated acetylsalicylic acid [100 milligram (mg)] orally once daily.
Subjects received 1 tablets of matching placebo orally once daily.
Overall Number of Participants Analyzed 6270 6276
Overall Number of Units Analyzed
Type of Units Analyzed: Days
1630 1630
Count of Units
Unit of Measure: Days
Days until 1% subjects had an efficacy event
528
  32.4%
381
  23.4%
Days until 2% subjects had an efficacy event
889
  54.5%
796
  48.8%
Days until 3% subjects had an efficacy event
1225
  75.2%
1134
  69.6%
Days until 4% subjects had an efficacy event
1630
 100.0%
1582
  97.1%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Acetylsalicylic Acid (Aspirin, BAYE4465), Placebo
Comments Primary efficacy analysis of time to the composite endpoint was conducted via a 2-sided log-rank test stratified for treatment, country, and sex. Results would be considered statistically significant and the primary objective of the study will have been met if the 2-sided P value is ≤0.05.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.597
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
2.Secondary Outcome
Title Time to the First Occurrence of the Composite Outcome of Cardiovascular Death, MI, or Stroke (Ischemic, Hemorrhagic, or Unknown)
Hide Description The time to Composite outcome consisting of the first occurrence of cardiovascular death, MI, or stroke (ischemic, hemorrhagic, or unknown) was defined as the number of days from the date of randomization to the date of the event confirmed by adjudication. The numbers of days for milestones when 1%, 2%, 3% and 4% of the subjects have reached endpoint events were estimated from Kaplan-Meier-Analyses.
Time Frame Until follow-up (approximate 6 years)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT
Arm/Group Title Acetylsalicylic Acid (Aspirin, BAYE4465) Placebo
Hide Arm/Group Description:
Subjects received 1 tablet of enteric-coated acetylsalicylic acid [100 milligram (mg)] orally once daily.
Subjects received 1 tablets of matching placebo orally once daily.
Overall Number of Participants Analyzed 6270 6276
Overall Number of Units Analyzed
Type of Units Analyzed: Days
1949 1949
Count of Units
Unit of Measure: Days
Days until 1% subjects had an efficacy event
678
  34.8%
522
  26.8%
Days until 2% subjects had an efficacy event
1167
  59.9%
1053
  54.0%
Days until 3% subjects had an efficacy event
1599
  82.0%
1501
  77.0%
Days until 4% subjects had an efficacy event
1949
 100.0%
1930
  99.0%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Acetylsalicylic Acid (Aspirin, BAYE4465), Placebo
Comments Statistics for time to the composite endpoint was conducted via a 2-sided log-rank test stratified for treatment, country, and sex. Results would be considered statistically significant if the 2-sided P value is ≤0.05.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6125
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
3.Secondary Outcome
Title Time to the First Occurrence of the Individual Components of the Primary: Non-fatal MI, Total MI, Non-fatal Stroke, Total Stroke, Cardiovascular Death, UA and TIA
Hide Description The time to event was defined as the number of days from the date of randomization to the date of the event confirmed by adjudication. The numbers of days for milestones when 1%, 2%, 3% and 4% of the subjects have reached endpoint events were estimated from Kaplan-Meier-Analyses.
Time Frame Until follow-up (approximately 6 years)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT
Arm/Group Title Acetylsalicylic Acid (Aspirin, BAYE4465) Placebo
Hide Arm/Group Description:
Subjects received 1 tablet of enteric-coated acetylsalicylic acid [100 milligram (mg)] orally once daily.
Subjects received 1 tablets of matching placebo orally once daily.
Overall Number of Participants Analyzed 6270 6276
Overall Number of Units Analyzed
Type of Units Analyzed: Days
2128 2128
Count of Units
Unit of Measure: Days
Days until 1% subjects had non-fatal MI
1309
  61.5%
1085
  51.0%
Days until 2% subjects had non-fatal MI NA [1] 
2121
  99.7%
Days until 1% subjects had total MI
1216
  57.1%
1014
  47.7%
Days until 2% subjects had total MI
2128
 100.0%
1906
  89.6%
Days until 1% subjects had non-fatal stroke
1576
  74.1%
1650
  77.5%
Days until 2% subjects had non-fatal stroke NA [1]  NA [1] 
Days until 1% subjects had total stroke
1543
  72.5%
1627
  76.5%
Days until 2% subjects had total stroke NA [1]  NA [1] 
Days until 1% subjects had cardiovascular death NA [1]  NA [1] 
Days until 2% subjects had cardiovascular death NA [1]  NA [1] 
Days until 1% subjects had UA NA [1]  NA [1] 
Days until 2% subjects had UA NA [1]  NA [1] 
Days until 1% subjects had TIA NA [1]  NA [1] 
Days until 2% subjects had TIA NA [1]  NA [2] 
[1]
Not applicable (NA) indicates that these milestones did not occur before completion of the study.
[2]
Not applicable (NA) indicates that these milestones did not occur before completion of the study..
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Acetylsalicylic Acid (Aspirin, BAYE4465), Placebo
Comments Statistics for time to non-fatal MI was conducted via a 2-sided log-rank test stratified for treatment, country, and sex. Results would be considered statistically significant if the 2-sided P value is ≤0.05.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4505
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Acetylsalicylic Acid (Aspirin, BAYE4465), Placebo
Comments Statistics for time to total MI was conducted via a 2-sided log-rank test stratified for treatment, country, and sex. Results would be considered statistically significant if the 2-sided P value is ≤0.05.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.229
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Acetylsalicylic Acid (Aspirin, BAYE4465), Placebo
Comments Statistics for time to total non-fatal stroke was conducted via a 2-sided log-rank test stratified for treatment, country, and sex. Results would be considered statistically significant if the 2-sided P value is ≤0.05.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3947
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Acetylsalicylic Acid (Aspirin, BAYE4465), Placebo
Comments Statistics for time to total stroke was conducted via a 2-sided log-rank test stratified for treatment, country, and sex. Results would be considered statistically significant if the 2-sided P value is ≤0.05.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5125
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
4.Secondary Outcome
Title Time to All-cause Mortality, the First Occurrence of All Cancers Excluding Non-melanoma Skin Cancer (NMSC) and the First Occurrence of Colon Cancer
Hide Description The time to event was defined as the number of days from the date of randomization to the date of the event confirmed by adjudication. The numbers of days for milestones when 1%, 2%, 3% and 4% of the subjects have reached endpoint events were estimated from Kaplan-Meier-Analyses.
Time Frame Until follow-up (approximately 6 years)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT
Arm/Group Title Acetylsalicylic Acid (Aspirin, BAYE4465) Placebo
Hide Arm/Group Description:
Subjects received 1 tablet of enteric-coated acetylsalicylic acid [100 milligram (mg)] orally once daily.
Subjects received 1 tablets of matching placebo orally once daily.
Overall Number of Participants Analyzed 6270 6276
Overall Number of Units Analyzed
Type of Units Analyzed: Days
1970 1970
Count of Units
Unit of Measure: Days
Days until 1% subjects had all-cause mortality
838
  42.5%
938
  47.6%
Days until 2% subjects had all-cause mortality
1493
  75.8%
1460
  74.1%
Days until 3% subjects had all-cause mortality
1970
 100.0%
1963
  99.6%
Days until 4% subjects had all-cause mortality NA [1]  NA [1] 
Days until 1% subjects had all cancer excl. NMSC
374
  19.0%
420
  21.3%
Days until 2% subjects had all cancer excl. NMSC
849
  43.1%
805
  40.9%
Days until 3% subjects had all cancer excl. NMSC
1164
  59.1%
1276
  64.8%
Days until 4% subjects had all cancer excl. NMSC
1542
  78.3%
1751
  88.9%
Days until 1% subjects had colon cancer NA [1]  NA [1] 
Days until 2% subjects had colon cancer NA [1]  NA [2] 
Days until 3% subjects had colon cancer NA [1]  NA [1] 
Days until 4% subjects had colon cancer NA [1]  NA [2] 
[1]
Not applicable (NA) indicates that these milestones did not occur before completion of the study.
[2]
Not applicable (NA) indicates that these milestones did not occur before completion of the study..
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Acetylsalicylic Acid (Aspirin, BAYE4465), Placebo
Comments Analysis of time to all-cause mortality was conducted via a 2-sided log-rank test stratified for treatment, country, and sex. Results would be considered statistically significant if the 2-sided P value is ≤0.05.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9544
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Acetylsalicylic Acid (Aspirin, BAYE4465), Placebo
Comments Analysis of time to the first occurrence of all cancers excluding non-melanoma skin cancer was conducted via a 2-sided log-rank test stratified for treatment, country, and sex. Results would be considered statistically significant if the 2-sided P value is ≤0.05.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4422
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Acetylsalicylic Acid (Aspirin, BAYE4465), Placebo
Comments Analysis of time to the first occurence colon cancer was conducted via a 2-sided log-rank test stratified for treatment, country, and sex. Results would be considered statistically significant if the 2-sided P value is ≤0.05.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.611
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
5.Secondary Outcome
Title Incidence of All-cause Mortality, All Cancers Excluding Non-melanoma Skin Cancer and Colon Cancer
Hide Description [Not Specified]
Time Frame Until follow-up (approximately 6 years)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT
Arm/Group Title Acetylsalicylic Acid (Aspirin, BAYE4465) Placebo
Hide Arm/Group Description:
Subjects received 1 tablet of enteric-coated acetylsalicylic acid [100 milligram (mg)] orally once daily.
Subjects received 1 tablets of matching placebo orally once daily.
Overall Number of Participants Analyzed 6270 6276
Measure Type: Number
Unit of Measure: Percentage of participants
all-cause mortality 2.55 2.57
all cancers excluding non-melanoma skin cancer 4.02 3.76
colon cancer 0.48 0.41
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Acetylsalicylic Acid (Aspirin, BAYE4465), Placebo
Comments Analysis of incidence of all-cause mortality was conducted via a 2-sided log-rank test. Results would be considered statistically significant if the 2-sided P value is ≤0.05.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9459
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Cox Proportional Hazard
Estimated Value 0.99
Confidence Interval (2-Sided) 95%
0.80 to 1.24
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Incidence of Confirmed MI, Stroke, Cardiovascular Death, UA, and TIA Separately
Hide Description The percentages of subjects with the efficacy endpoints of confirmed MI, stroke, cardiovascular death, UA and TIA are reported separately. *all other CV death without fatal MI and fatal stroke
Time Frame Until follow-up (approximately 6 years)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT
Arm/Group Title Acetylsalicylic Acid (Aspirin, BAYE4465) Placebo
Hide Arm/Group Description:
Subjects received 1 tablet of enteric-coated acetylsalicylic acid [100 milligram (mg)] orally once daily.
Subjects received 1 tablets of matching placebo orally once daily.
Overall Number of Participants Analyzed 6270 6276
Measure Type: Number
Unit of Measure: Percentage of participants
MI 1.52 1.78
stroke 1.20 1.07
CV death* 0.61 0.62
UA 0.32 0.32
TIA 0.67 0.72
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Acetylsalicylic Acid (Aspirin, BAYE4465), Placebo
Comments Analysis of incidence of MI was conducted via a 2-sided log-rank test. Results would be considered statistically significant if the 2-sided P value is ≤0.05.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2325
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Cox Proportional Hazard
Estimated Value 0.85
Confidence Interval (2-Sided) 95%
0.64 to 1.11
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Acetylsalicylic Acid (Aspirin, BAYE4465), Placebo
Comments Analysis of incidence of stroke was conducted via a 2-sided log-rank test. Results would be considered statistically significant if the 2-sided P value is ≤0.05.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5072
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Cox Proportional Hazard
Estimated Value 1.12
Confidence Interval 95%
0.80 to 1.55
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Acetylsalicylic Acid (Aspirin, BAYE4465), Placebo
Comments Analysis of incidence of cardiovascular death was conducted via a 2-sided log-rank test. Results would be considered statistically significant if the 2-sided P value is ≤0.05.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9010
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Cox Proportional Hazard
Estimated Value 0.97
Confidence Interval 95%
0.62 to 1.52
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Acetylsalicylic Acid (Aspirin, BAYE4465), Placebo
Comments Analysis of incidence of UA was conducted via a 2-sided log-rank test. Results would be considered statistically significant if the 2-sided P value is ≤0.05.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9979
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Cox Proportional Hazard
Estimated Value 1.00
Confidence Interval (2-Sided) 95%
0.54 to 1.86
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Acetylsalicylic Acid (Aspirin, BAYE4465), Placebo
Comments Analysis of incidence of TIA was conducted via a 2-sided log-rank test. Results would be considered statistically significant if the 2-sided P value is ≤0.05.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7455
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Cox Proportional Hazard
Estimated Value 0.93
Confidence Interval (2-Sided) 95%
0.61 to 1.42
Estimation Comments [Not Specified]
7.Other Pre-specified Outcome
Title Number of Subjects With Adjudicated GI Bleeding by Severity
Hide Description [Not Specified]
Time Frame Until follow-up (approximate 6 years)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT
Arm/Group Title Acetylsalicylic Acid (Aspirin, BAYE4465) Placebo
Hide Arm/Group Description:
Subjects received 1 tablet of enteric-coated acetylsalicylic acid [100 milligram (mg)] orally once daily.
Subjects received 1 tablets of matching placebo orally once daily.
Overall Number of Participants Analyzed 6270 6276
Measure Type: Count of Participants
Unit of Measure: Participants
Total
61
   1.0%
29
   0.5%
Mild
42
   0.7%
22
   0.4%
Moderate
15
   0.2%
5
   0.1%
Severe
4
   0.1%
2
   0.0%
8.Other Pre-specified Outcome
Title Incidence of Composite Outcomes and Non-fatal MI
Hide Description [Not Specified]
Time Frame Until follow-up (approximate 6 years)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT
Arm/Group Title Acetylsalicylic Acid (Aspirin, BAYE4465) Placebo
Hide Arm/Group Description:
Subjects received 1 tablet of enteric-coated acetylsalicylic acid [100 milligram (mg)] orally once daily.
Subjects received 1 tablets of matching placebo orally once daily.
Overall Number of Participants Analyzed 6270 6276
Measure Type: Number
Unit of Measure: Percentage of participants
MI, stroke, CV death, UA or TIA 4.29 4.48
MI, stroke or CV death 3.32 3.47
non-fatal MI 1.40 1.56
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Acetylsalicylic Acid (Aspirin, BAYE4465), Placebo
Comments Analysis of incidence of composite outcome of MI, stroke, CV death, UA or TIA was conducted via a 2-sided log-rank test. Results would be considered statistically significant if the 2-sided P value is ≤0.05.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6038
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Cox Proportional Hazard
Estimated Value 0.96
Confidence Interval (2-Sided) 95%
0.81 to 1.13
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Acetylsalicylic Acid (Aspirin, BAYE4465), Placebo
Comments Analysis of incidence of composite outcome of MI, stroke or CV death was conducted via a 2-sided log-rank test. Results would be considered statistically significant if the 2-sided P value is ≤0.05.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6190
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Cox Proportional Hazard
Estimated Value 0.95
Confidence Interval (2-Sided) 95%
0.79 to 1.15
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Acetylsalicylic Acid (Aspirin, BAYE4465), Placebo
Comments Analysis of incidence of non-fatal MI was conducted via a 2-sided log-rank test. Results would be considered statistically significant if the 2-sided P value is ≤0.05.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4562
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Cox Proportional Hazard
Estimated Value 0.90
Confidence Interval (2-Sided) 95%
0.67 to 1.20
Estimation Comments [Not Specified]
9.Other Pre-specified Outcome
Title Incidence of Composite Outcomes and Individual Outcomes in Per-protocol Population
Hide Description *all other CV death without fatal MI and fatal stroke.
Time Frame Until follow-up (approximate 6 years)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Per-protocol (PP) group (N=7702) consists of all patients who had no protocol violation.
Arm/Group Title Acetylsalicylic Acid (Aspirin, BAYE4465) Per-protocol Placebo Per-protocol
Hide Arm/Group Description:
Subjects received 1 tablet of enteric-coated acetylsalicylic acid [100 milligram (mg)] orally once daily.
Subjects received 1 tablets of matching placebo orally once daily.
Overall Number of Participants Analyzed 3790 3912
Measure Type: Number
Unit of Measure: Percentage of participants
MI, stroke, CV death, UA or TIA 3.40 4.19
MI, stroke or CV death 2.72 3.45
MI 0.98 1.84
Non-fatal MI 0.84 1.53
Stroke 1.06 0.95
CV death* 0.69 0.66
UA 0.21 0.28
TIA 0.50 0.49
All-cause mortality 2.85 2.58
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Acetylsalicylic Acid (Aspirin, BAYE4465) Per-protocol, Placebo Per-protocol
Comments Analysis of incidence of composite outcome of MI, stroke, CV death, UA or TIA was conducted via a 2-sided log-rank test. Results would be considered statistically significant if the 2-sided P value is ≤0.05.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0756
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Cox Proportional Hazard
Estimated Value 0.81
Confidence Interval (2-Sided) 95%
0.64 to 1.02
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Acetylsalicylic Acid (Aspirin, BAYE4465) Per-protocol, Placebo Per-protocol
Comments Analysis of incidence of composite outcome of MI, stroke or CV death was conducted via a 2-sided log-rank test. Results would be considered statistically significant if the 2-sided P value is ≤0.05.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0661
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Cox Proportional Hazard
Estimated Value 0.79
Confidence Interval (2-Sided) 95%
0.61 to 1.02
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Acetylsalicylic Acid (Aspirin, BAYE4465) Per-protocol, Placebo Per-protocol
Comments Analysis of incidence of MI was conducted via a 2-sided log-rank test. Results would be considered statistically significant if the 2-sided P value is ≤0.05.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0014
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Cox Proportional Hazard
Estimated Value 0.53
Confidence Interval (2-Sided) 95%
0.36 to 0.79
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Acetylsalicylic Acid (Aspirin, BAYE4465) Per-protocol, Placebo Per-protocol
Comments Analysis of incidence of non-fatal MI was conducted via a 2-sided log-rank test. Results would be considered statistically significant if the 2-sided P value is ≤0.05.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0056
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Cox Proportional Hazard
Estimated Value 0.55
Confidence Interval (2-Sided) 95%
0.36 to 0.84
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Acetylsalicylic Acid (Aspirin, BAYE4465) Per-protocol, Placebo Per-protocol
Comments Analysis of incidence of stroke was conducted via a 2-sided log-rank test. Results would be considered statistically significant if the 2-sided P value is ≤0.05.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6291
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Cox Proportional Hazard
Estimated Value 1.12
Confidence Interval 95%
0.71 to 1.75
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Acetylsalicylic Acid (Aspirin, BAYE4465) Per-protocol, Placebo Per-protocol
Comments Analysis of incidence of CV death was conducted via a 2-sided log-rank test. Results would be considered statistically significant if the 2-sided P value is ≤0.05.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9161
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Cox Proportional Hazard
Estimated Value 1.03
Confidence Interval (2-Sided) 95%
0.60 to 1.77
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Acetylsalicylic Acid (Aspirin, BAYE4465) Per-protocol, Placebo Per-protocol
Comments Analysis of incidence of UA was conducted via a 2-sided log-rank test. Results would be considered statistically significant if the 2-sided P value is ≤0.05.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5380
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Cox Proportional Hazard
Estimated Value 0.75
Confidence Interval 95%
0.30 to 1.87
Estimation Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Acetylsalicylic Acid (Aspirin, BAYE4465) Per-protocol, Placebo Per-protocol
Comments Analysis of incidence of TIA was conducted via a 2-sided log-rank test. Results would be considered statistically significant if the 2-sided P value is ≤0.05.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9181
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Cox Proportional Hazard
Estimated Value 1.03
Confidence Interval (2-Sided) 95%
0.55 to 1.95
Estimation Comments [Not Specified]
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Acetylsalicylic Acid (Aspirin, BAYE4465) Per-protocol, Placebo Per-protocol
Comments Analysis of incidence of all-cause mortality was conducted via a 2-sided log-rank test. Results would be considered statistically significant if the 2-sided P value is ≤0.05.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4796
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Cox Proportional Hazard
Estimated Value 1.10
Confidence Interval (2-Sided) 95%
0.84 to 1.45
Estimation Comments [Not Specified]
Time Frame Until follow-up (approximately 6 years)
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Placebo Acetylsalicylic Acid
Hide Arm/Group Description Subjects received 1 tablets of matching placebo orally once daily. Subjects received 1 tablet of enteric-coated acetylsalicylic acid [100 milligram (mg)] orally one daily.
All-Cause Mortality
Placebo Acetylsalicylic Acid
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Placebo Acetylsalicylic Acid
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1311/6276 (20.89%)      1266/6270 (20.19%)    
Blood and lymphatic system disorders     
Abdominal lymphadenopathy * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Anaemia * 1  4/6276 (0.06%)  4 6/6270 (0.10%)  6
Febrile neutropenia * 1  1/6276 (0.02%)  2 0/6270 (0.00%)  0
Haemorrhagic anaemia * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Hypochromic anaemia * 1  1/6276 (0.02%)  1 1/6270 (0.02%)  1
Iron deficiency anaemia * 1  3/6276 (0.05%)  3 3/6270 (0.05%)  3
Leukocytosis * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Lymphadenitis * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Lymphadenopathy * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Neutropenia * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Thrombocytopenia * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Cardiac disorders     
Acute coronary syndrome * 1  12/6276 (0.19%)  12 10/6270 (0.16%)  10
Acute left ventricular failure * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Acute myocardial infarction * 1  58/6276 (0.92%)  58 43/6270 (0.69%)  44
Angina pectoris * 1  14/6276 (0.22%)  15 20/6270 (0.32%)  20
Angina unstable * 1  19/6276 (0.30%)  20 15/6270 (0.24%)  17
Aortic valve calcification * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Aortic valve disease * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Aortic valve disease mixed * 1  2/6276 (0.03%)  2 0/6270 (0.00%)  0
Aortic valve incompetence * 1  4/6276 (0.06%)  4 1/6270 (0.02%)  1
Aortic valve stenosis * 1  5/6276 (0.08%)  5 3/6270 (0.05%)  3
Arteriosclerosis coronary artery * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Arteriospasm coronary * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Atrial fibrillation * 1  40/6276 (0.64%)  41 37/6270 (0.59%)  39
Atrial flutter * 1  3/6276 (0.05%)  3 2/6270 (0.03%)  2
Atrial thrombosis * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Atrioventricular block * 1  0/6276 (0.00%)  0 2/6270 (0.03%)  2
Atrioventricular block complete * 1  4/6276 (0.06%)  4 2/6270 (0.03%)  2
Atrioventricular block first degree * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Atrioventricular block second degree * 1  8/6276 (0.13%)  8 0/6270 (0.00%)  0
Bradycardia * 1  4/6276 (0.06%)  4 0/6270 (0.00%)  0
Bundle branch block right * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Cardiac arrest * 1  9/6276 (0.14%)  9 4/6270 (0.06%)  4
Cardiac disorder * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Cardiac failure * 1  3/6276 (0.05%)  3 7/6270 (0.11%)  7
Cardiac failure acute * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Cardiac failure chronic * 1  4/6276 (0.06%)  4 0/6270 (0.00%)  0
Cardiac failure congestive * 1  3/6276 (0.05%)  3 1/6270 (0.02%)  1
Cardiac ventricular thrombosis * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Cardiogenic shock * 1  3/6276 (0.05%)  3 3/6270 (0.05%)  3
Cardiopulmonary failure * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Congestive cardiomyopathy * 1  0/6276 (0.00%)  0 2/6270 (0.03%)  2
Coronary artery disease * 1  61/6276 (0.97%)  63 46/6270 (0.73%)  46
Coronary artery occlusion * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Coronary artery stenosis * 1  3/6276 (0.05%)  3 1/6270 (0.02%)  1
Coronary artery thrombosis * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Coronary ostial stenosis * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Dressler's syndrome * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Extrasystoles * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Left ventricular dysfunction * 1  1/6276 (0.02%)  1 1/6270 (0.02%)  1
Left ventricular failure * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  2
Left ventricular hypertrophy * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Mitral valve incompetence * 1  4/6276 (0.06%)  4 1/6270 (0.02%)  1
Mitral valve prolapse * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Myocardial fibrosis * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Myocardial infarction * 1  38/6276 (0.61%)  38 29/6270 (0.46%)  29
Myocardial ischaemia * 1  10/6276 (0.16%)  10 7/6270 (0.11%)  7
Palpitations * 1  1/6276 (0.02%)  1 1/6270 (0.02%)  1
Pericarditis * 1  0/6276 (0.00%)  0 2/6270 (0.03%)  2
Pleuropericarditis * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Prinzmetal angina * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Right ventricular failure * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Silent myocardial infarction * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Sinoatrial block * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Sinus bradycardia * 1  1/6276 (0.02%)  1 1/6270 (0.02%)  1
Sinus node dysfunction * 1  2/6276 (0.03%)  2 2/6270 (0.03%)  2
Sinus tachycardia * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Supraventricular tachycardia * 1  1/6276 (0.02%)  1 1/6270 (0.02%)  1
Tachyarrhythmia * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Tachycardia paroxysmal * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Torsade de pointes * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Tricuspid valve incompetence * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Ventricular arrhythmia * 1  0/6276 (0.00%)  0 2/6270 (0.03%)  2
Ventricular extrasystoles * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Ventricular fibrillation * 1  4/6276 (0.06%)  4 2/6270 (0.03%)  2
Ventricular tachycardia * 1  2/6276 (0.03%)  2 0/6270 (0.00%)  0
Congenital, familial and genetic disorders     
Congenital cystic kidney disease * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Congenital urinary tract obstruction * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Familial tremor * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Haemophilia * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Hydrocele * 1  2/6276 (0.03%)  3 1/6270 (0.02%)  1
Myocardial bridging * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Odontogenic cyst * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Type IIa hyperlipidaemia * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Ear and labyrinth disorders     
Deafness unilateral * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Hypoacusis * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Inner ear disorder * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Meniere's disease * 1  1/6276 (0.02%)  1 1/6270 (0.02%)  1
Tinnitus * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Tympanic membrane perforation * 1  0/6276 (0.00%)  0 2/6270 (0.03%)  2
Vertigo * 1  2/6276 (0.03%)  2 2/6270 (0.03%)  2
Vertigo positional * 1  2/6276 (0.03%)  2 1/6270 (0.02%)  1
Endocrine disorders     
Goitre * 1  4/6276 (0.06%)  4 6/6270 (0.10%)  6
Hyperparathyroidism * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Hyperthyroidism * 1  2/6276 (0.03%)  2 0/6270 (0.00%)  0
Thyroid cyst * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Toxic nodular goitre * 1  1/6276 (0.02%)  1 3/6270 (0.05%)  3
Eye disorders     
Amaurosis fugax * 1  1/6276 (0.02%)  1 2/6270 (0.03%)  2
Cataract * 1  5/6276 (0.08%)  5 8/6270 (0.13%)  10
Chalazion * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Conjunctival haemorrhage * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Corneal degeneration * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Corneal disorder * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Endocrine ophthalmopathy * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Eye disorder * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Eye haemorrhage * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Eyelid dermatochalasis * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Eyelid ptosis * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Glaucoma * 1  3/6276 (0.05%)  3 4/6270 (0.06%)  4
Lacrimation increased * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Macular fibrosis * 1  1/6276 (0.02%)  1 1/6270 (0.02%)  1
Macular hole * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Optic ischaemic neuropathy * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Polypoidal choroidal vasculopathy * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Retinal artery embolism * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Retinal artery occlusion * 1  2/6276 (0.03%)  2 0/6270 (0.00%)  0
Retinal detachment * 1  3/6276 (0.05%)  4 3/6270 (0.05%)  3
Retinal haemorrhage * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Retinal tear * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Retinal vein occlusion * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Retinal vein thrombosis * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Strabismus * 1  1/6276 (0.02%)  1 1/6270 (0.02%)  1
Vision blurred * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Vitreous haemorrhage * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Gastrointestinal disorders     
Abdominal discomfort * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Abdominal distension * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Abdominal hernia * 1  3/6276 (0.05%)  3 1/6270 (0.02%)  1
Abdominal pain * 1  10/6276 (0.16%)  11 11/6270 (0.18%)  11
Abdominal pain lower * 1  2/6276 (0.03%)  2 0/6270 (0.00%)  0
Abdominal pain upper * 1  2/6276 (0.03%)  2 1/6270 (0.02%)  1
Anal fistula * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Anal haemorrhage * 1  1/6276 (0.02%)  1 1/6270 (0.02%)  1
Ascites * 1  0/6276 (0.00%)  0 2/6270 (0.03%)  2
Barrett's oesophagus * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Change of bowel habit * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Chronic gastritis * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Colitis * 1  1/6276 (0.02%)  1 2/6270 (0.03%)  2
Colitis ischaemic * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Colitis ulcerative * 1  1/6276 (0.02%)  1 1/6270 (0.02%)  1
Colon dysplasia * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Constipation * 1  2/6276 (0.03%)  2 3/6270 (0.05%)  3
Diarrhoea * 1  1/6276 (0.02%)  1 3/6270 (0.05%)  3
Diverticulum * 1  0/6276 (0.00%)  0 4/6270 (0.06%)  4
Diverticulum intestinal * 1  0/6276 (0.00%)  0 2/6270 (0.03%)  2
Duodenal stenosis * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Duodenal ulcer * 1  3/6276 (0.05%)  3 1/6270 (0.02%)  1
Duodenal ulcer haemorrhage * 1  2/6276 (0.03%)  2 2/6270 (0.03%)  2
Duodenal ulcer perforation * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Duodenitis * 1  2/6276 (0.03%)  2 0/6270 (0.00%)  0
Dyspepsia * 1  1/6276 (0.02%)  1 1/6270 (0.02%)  1
Dysphagia * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Enterovesical fistula * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Faecaloma * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Faeces discoloured * 1  1/6276 (0.02%)  1 1/6270 (0.02%)  1
Femoral hernia * 1  3/6276 (0.05%)  3 0/6270 (0.00%)  0
Food poisoning * 1  3/6276 (0.05%)  3 0/6270 (0.00%)  0
Gastric haemorrhage * 1  2/6276 (0.03%)  2 0/6270 (0.00%)  0
Gastric polyps * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Gastric ulcer * 1  1/6276 (0.02%)  1 4/6270 (0.06%)  4
Gastric ulcer haemorrhage * 1  1/6276 (0.02%)  1 3/6270 (0.05%)  3
Gastric ulcer perforation * 1  0/6276 (0.00%)  0 2/6270 (0.03%)  2
Gastritis * 1  2/6276 (0.03%)  2 2/6270 (0.03%)  2
Gastritis erosive * 1  3/6276 (0.05%)  3 2/6270 (0.03%)  2
Gastrointestinal angiodysplasia * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Gastrointestinal disorder * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Gastrointestinal haemorrhage * 1  2/6276 (0.03%)  2 13/6270 (0.21%)  13
Gastrointestinal obstruction * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Gastrooesophageal reflux disease * 1  1/6276 (0.02%)  1 2/6270 (0.03%)  2
Haematemesis * 1  1/6276 (0.02%)  1 3/6270 (0.05%)  3
Haematochezia * 1  2/6276 (0.03%)  2 0/6270 (0.00%)  0
Haemorrhagic erosive gastritis * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Haemorrhoidal haemorrhage * 1  1/6276 (0.02%)  1 1/6270 (0.02%)  1
Haemorrhoids * 1  2/6276 (0.03%)  2 4/6270 (0.06%)  4
Haemorrhoids thrombosed * 1  3/6276 (0.05%)  3 0/6270 (0.00%)  0
Hiatus hernia * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Ileus * 1  2/6276 (0.03%)  2 0/6270 (0.00%)  0
Ileus paralytic * 1  1/6276 (0.02%)  1 1/6270 (0.02%)  1
Incarcerated inguinal hernia * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Inflammatory bowel disease * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Inguinal hernia * 1  31/6276 (0.49%)  32 35/6270 (0.56%)  35
Inguinal hernia strangulated * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Intestinal fibrosis * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Intestinal haemorrhage * 1  0/6276 (0.00%)  0 2/6270 (0.03%)  2
Intestinal ischaemia * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Intestinal obstruction * 1  1/6276 (0.02%)  1 3/6270 (0.05%)  4
Intestinal perforation * 1  1/6276 (0.02%)  1 1/6270 (0.02%)  1
Intestinal polyp * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Irritable bowel syndrome * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Large intestinal haemorrhage * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Large intestine perforation * 1  0/6276 (0.00%)  0 3/6270 (0.05%)  3
Large intestine polyp * 1  2/6276 (0.03%)  2 4/6270 (0.06%)  6
Leukoplakia oral * 1  0/6276 (0.00%)  0 3/6270 (0.05%)  3
Lower gastrointestinal haemorrhage * 1  0/6276 (0.00%)  0 3/6270 (0.05%)  4
Mallory-Weiss syndrome * 1  0/6276 (0.00%)  0 2/6270 (0.03%)  2
Mechanical ileus * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Melaena * 1  2/6276 (0.03%)  2 2/6270 (0.03%)  2
Mesenteric vein thrombosis * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Nausea * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Oesophageal achalasia * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Oesophageal obstruction * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Oesophageal stenosis * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Oesophageal ulcer * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Oesophageal ulcer haemorrhage * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Oesophageal varices haemorrhage * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Oesophagitis ulcerative * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Oral mucosal hypertrophy * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Pancreatic pseudocyst * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Pancreatitis * 1  1/6276 (0.02%)  1 3/6270 (0.05%)  3
Pancreatitis acute * 1  3/6276 (0.05%)  3 5/6270 (0.08%)  5
Pancreatitis necrotising * 1  1/6276 (0.02%)  1 1/6270 (0.02%)  1
Rectal fissure * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Rectal haemorrhage * 1  3/6276 (0.05%)  3 6/6270 (0.10%)  6
Retroperitoneal haemorrhage * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Small intestinal obstruction * 1  3/6276 (0.05%)  3 2/6270 (0.03%)  2
Subileus * 1  0/6276 (0.00%)  0 3/6270 (0.05%)  3
Thrombosis mesenteric vessel * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Umbilical hernia * 1  4/6276 (0.06%)  4 5/6270 (0.08%)  5
Upper gastrointestinal haemorrhage * 1  4/6276 (0.06%)  4 1/6270 (0.02%)  1
Vomiting * 1  1/6276 (0.02%)  1 2/6270 (0.03%)  2
General disorders     
Chest discomfort * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Chest pain * 1  19/6276 (0.30%)  19 23/6270 (0.37%)  24
Death * 1  3/6276 (0.05%)  3 3/6270 (0.05%)  3
Feeling abnormal * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Hernia * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Impaired healing * 1  2/6276 (0.03%)  2 1/6270 (0.02%)  1
Injection site injury * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Malaise * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Medical device pain * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Multiple organ dysfunction syndrome * 1  3/6276 (0.05%)  3 2/6270 (0.03%)  2
Non-cardiac chest pain * 1  2/6276 (0.03%)  2 2/6270 (0.03%)  2
Oedema * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Oedema peripheral * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Organ failure * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Performance status decreased * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Peripheral swelling * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Pyrexia * 1  1/6276 (0.02%)  1 2/6270 (0.03%)  2
Sudden cardiac death * 1  1/6276 (0.02%)  1 2/6270 (0.03%)  2
Sudden death * 1  1/6276 (0.02%)  1 1/6270 (0.02%)  1
Systemic inflammatory response syndrome * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Unevaluable event * 1  1/6276 (0.02%)  1 2/6270 (0.03%)  2
Vascular stent occlusion * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Vascular stent thrombosis * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Hepatobiliary disorders     
Alcoholic liver disease * 1  1/6276 (0.02%)  1 1/6270 (0.02%)  1
Bile duct stone * 1  1/6276 (0.02%)  1 4/6270 (0.06%)  4
Biliary cirrhosis primary * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Biliary colic * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Biliary cyst * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Biliary dilatation * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Biliary fistula * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Cholecystitis * 1  8/6276 (0.13%)  9 13/6270 (0.21%)  13
Cholecystitis acute * 1  8/6276 (0.13%)  8 7/6270 (0.11%)  7
Cholecystitis chronic * 1  1/6276 (0.02%)  1 1/6270 (0.02%)  1
Cholelithiasis * 1  17/6276 (0.27%)  17 24/6270 (0.38%)  24
Cholestasis * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Gallbladder enlargement * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Gallbladder perforation * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Gallbladder polyp * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Hepatic cirrhosis * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Hepatic pain * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Hepatitis * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Hepatitis acute * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Hepatotoxicity * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Jaundice * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Liver disorder * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Liver injury * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Immune system disorders     
Allergy to arthropod sting * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  2
Anaphylactic reaction * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Drug hypersensitivity * 1  1/6276 (0.02%)  1 1/6270 (0.02%)  1
Infections and infestations     
Abdominal sepsis * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Abdominal wall abscess * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Acute sinusitis * 1  0/6276 (0.00%)  0 2/6270 (0.03%)  3
Anal abscess * 1  1/6276 (0.02%)  1 1/6270 (0.02%)  1
Anal fistula infection * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Appendicitis * 1  9/6276 (0.14%)  10 9/6270 (0.14%)  9
Appendicitis perforated * 1  3/6276 (0.05%)  3 1/6270 (0.02%)  1
Arthritis bacterial * 1  2/6276 (0.03%)  2 0/6270 (0.00%)  0
Arthritis infective * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Atypical pneumonia * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Bacteraemia * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Bone tuberculosis * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Bronchitis * 1  1/6276 (0.02%)  1 2/6270 (0.03%)  2
Campylobacter gastroenteritis * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Cellulitis * 1  8/6276 (0.13%)  8 6/6270 (0.10%)  6
Cellulitis orbital * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Chlamydial infection * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Cholecystitis infective * 1  1/6276 (0.02%)  1 1/6270 (0.02%)  1
Chronic sinusitis * 1  0/6276 (0.00%)  0 2/6270 (0.03%)  2
Colonic abscess * 1  0/6276 (0.00%)  0 2/6270 (0.03%)  2
Cystitis * 1  1/6276 (0.02%)  1 2/6270 (0.03%)  2
Device related infection * 1  0/6276 (0.00%)  0 2/6270 (0.03%)  2
Diverticulitis * 1  7/6276 (0.11%)  8 5/6270 (0.08%)  5
Diverticulitis intestinal haemorrhagic * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Dural abscess * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Ear infection * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Encephalitis * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Endocarditis * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Endocarditis bacterial * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Epididymitis * 1  1/6276 (0.02%)  1 1/6270 (0.02%)  1
Erysipelas * 1  1/6276 (0.02%)  2 2/6270 (0.03%)  3
Extradural abscess * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Gangrene * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Gastroenteritis * 1  4/6276 (0.06%)  4 6/6270 (0.10%)  6
Gastroenteritis norovirus * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Gastroenteritis salmonella * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Gastroenteritis viral * 1  1/6276 (0.02%)  1 1/6270 (0.02%)  1
Helicobacter gastritis * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Herpes zoster infection neurological * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Herpes zoster meningoencephalitis * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Infection * 1  2/6276 (0.03%)  2 0/6270 (0.00%)  0
Infectious pleural effusion * 1  1/6276 (0.02%)  1 1/6270 (0.02%)  1
Infective exacerbation of chronic obstructive airways disease * 1  4/6276 (0.06%)  5 7/6270 (0.11%)  11
Kidney infection * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Labyrinthitis * 1  1/6276 (0.02%)  1 3/6270 (0.05%)  3
Lower respiratory tract infection * 1  4/6276 (0.06%)  4 3/6270 (0.05%)  3
Lower respiratory tract infection viral * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Meningitis meningococcal * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Meningitis viral * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Muscle abscess * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Neutropenic sepsis * 1  1/6276 (0.02%)  1 2/6270 (0.03%)  2
Ophthalmic herpes zoster * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Orchitis * 1  3/6276 (0.05%)  3 0/6270 (0.00%)  0
Osteomyelitis * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Otitis externa * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Otitis media chronic * 1  1/6276 (0.02%)  2 0/6270 (0.00%)  0
Pancreas infection * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Paronychia * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Perihepatic abscess * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Perineal abscess * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Peritonitis * 1  0/6276 (0.00%)  0 4/6270 (0.06%)  4
Peritonsillar abscess * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Peritonsillitis * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Pharyngitis * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Pilonidal cyst * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Pleural infection * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Pneumonia * 1  19/6276 (0.30%)  19 26/6270 (0.41%)  28
Pneumonia bacterial * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Pneumonia influenzal * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Pneumonia legionella * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Postoperative wound infection * 1  1/6276 (0.02%)  1 2/6270 (0.03%)  2
Pseudomembranous colitis * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Pseudomonal sepsis * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Pulmonary sepsis * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Pulmonary tuberculosis * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Pyelocystitis * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Pyelonephritis * 1  1/6276 (0.02%)  1 2/6270 (0.03%)  2
Pyelonephritis acute * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Respiratory tract infection * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Rhinitis * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Scrotal abscess * 1  1/6276 (0.02%)  2 1/6270 (0.02%)  1
Sepsis * 1  6/6276 (0.10%)  6 4/6270 (0.06%)  5
Septic shock * 1  3/6276 (0.05%)  3 0/6270 (0.00%)  0
Sinusitis * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Subcutaneous abscess * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  2
Subdiaphragmatic abscess * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Upper respiratory tract infection * 1  2/6276 (0.03%)  2 0/6270 (0.00%)  0
Urinary tract infection * 1  7/6276 (0.11%)  7 9/6270 (0.14%)  9
Urosepsis * 1  4/6276 (0.06%)  4 2/6270 (0.03%)  2
Vestibular neuronitis * 1  1/6276 (0.02%)  1 1/6270 (0.02%)  1
Viral infection * 1  1/6276 (0.02%)  1 1/6270 (0.02%)  1
Wound infection * 1  1/6276 (0.02%)  1 1/6270 (0.02%)  1
Yersinia infection * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Injury, poisoning and procedural complications     
Accident at work * 1  1/6276 (0.02%)  1 1/6270 (0.02%)  1
Acetabulum fracture * 1  1/6276 (0.02%)  1 1/6270 (0.02%)  2
Alcohol poisoning * 1  1/6276 (0.02%)  1 1/6270 (0.02%)  1
Anaemia postoperative * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Ankle fracture * 1  9/6276 (0.14%)  9 13/6270 (0.21%)  13
Arterial bypass occlusion * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Bone contusion * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Carbon monoxide poisoning * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Cervical vertebral fracture * 1  2/6276 (0.03%)  2 2/6270 (0.03%)  2
Chest injury * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Clavicle fracture * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Concussion * 1  3/6276 (0.05%)  4 1/6270 (0.02%)  1
Contusion * 1  2/6276 (0.03%)  4 0/6270 (0.00%)  0
Craniocerebral injury * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Epicondylitis * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Extradural haematoma * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Eyelid injury * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Facial bones fracture * 1  3/6276 (0.05%)  4 0/6270 (0.00%)  0
Fall * 1  7/6276 (0.11%)  8 4/6270 (0.06%)  4
Femoral neck fracture * 1  9/6276 (0.14%)  10 3/6270 (0.05%)  3
Femur fracture * 1  6/6276 (0.10%)  6 4/6270 (0.06%)  4
Foot fracture * 1  2/6276 (0.03%)  2 3/6270 (0.05%)  3
Forearm fracture * 1  1/6276 (0.02%)  1 1/6270 (0.02%)  1
Foreign body * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Fractured ischium * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Gas poisoning * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Gastrointestinal anastomotic leak * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Hand fracture * 1  2/6276 (0.03%)  3 2/6270 (0.03%)  2
Head injury * 1  3/6276 (0.05%)  3 5/6270 (0.08%)  5
Hip fracture * 1  2/6276 (0.03%)  2 0/6270 (0.00%)  0
Humerus fracture * 1  11/6276 (0.18%)  12 2/6270 (0.03%)  2
Ilium fracture * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Incision site ulcer * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Incisional hernia * 1  2/6276 (0.03%)  2 3/6270 (0.05%)  3
Injury * 1  2/6276 (0.03%)  2 1/6270 (0.02%)  1
Intentional overdose * 1  1/6276 (0.02%)  1 1/6270 (0.02%)  1
Joint dislocation * 1  2/6276 (0.03%)  2 0/6270 (0.00%)  0
Joint injury * 1  0/6276 (0.00%)  0 2/6270 (0.03%)  2
Kidney contusion * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Laceration * 1  3/6276 (0.05%)  3 2/6270 (0.03%)  2
Ligament rupture * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Ligament sprain * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Limb injury * 1  1/6276 (0.02%)  1 1/6270 (0.02%)  1
Lower limb fracture * 1  2/6276 (0.03%)  3 1/6270 (0.02%)  1
Lumbar vertebral fracture * 1  3/6276 (0.05%)  4 3/6270 (0.05%)  3
Meniscus injury * 1  11/6276 (0.18%)  11 10/6270 (0.16%)  10
Multiple fractures * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Multiple injuries * 1  1/6276 (0.02%)  1 1/6270 (0.02%)  1
Muscle rupture * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Patella fracture * 1  2/6276 (0.03%)  2 1/6270 (0.02%)  1
Pelvic fracture * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Periprosthetic fracture * 1  1/6276 (0.02%)  1 1/6270 (0.02%)  1
Post concussion syndrome * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Post procedural discharge * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Post procedural haemorrhage * 1  1/6276 (0.02%)  1 2/6270 (0.03%)  2
Post procedural inflammation * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Post procedural myocardial infarction * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Procedural haemorrhage * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Procedural pain * 1  3/6276 (0.05%)  3 0/6270 (0.00%)  0
Radius fracture * 1  7/6276 (0.11%)  7 2/6270 (0.03%)  2
Rib fracture * 1  2/6276 (0.03%)  2 3/6270 (0.05%)  3
Road traffic accident * 1  4/6276 (0.06%)  4 0/6270 (0.00%)  0
Scapula fracture * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Skull fracture * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Skull fractured base * 1  1/6276 (0.02%)  1 1/6270 (0.02%)  1
Spinal compression fracture * 1  1/6276 (0.02%)  1 3/6270 (0.05%)  3
Spinal fracture * 1  4/6276 (0.06%)  4 0/6270 (0.00%)  0
Splenic rupture * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Stab wound * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Sternal fracture * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Stomal hernia * 1  1/6276 (0.02%)  1 1/6270 (0.02%)  1
Subarachnoid haemorrhage * 1  3/6276 (0.05%)  3 6/6270 (0.10%)  6
Subcutaneous haematoma * 1  0/6276 (0.00%)  0 2/6270 (0.03%)  2
Subdural haematoma * 1  3/6276 (0.05%)  3 2/6270 (0.03%)  2
Subdural haemorrhage * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Synovial rupture * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Tendon injury * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Tendon rupture * 1  5/6276 (0.08%)  5 4/6270 (0.06%)  4
Thermal burn * 1  1/6276 (0.02%)  2 1/6270 (0.02%)  2
Thoracic vertebral fracture * 1  2/6276 (0.03%)  2 4/6270 (0.06%)  4
Tibia fracture * 1  2/6276 (0.03%)  2 3/6270 (0.05%)  3
Traumatic haemothorax * 1  1/6276 (0.02%)  1 1/6270 (0.02%)  1
Traumatic intracranial haemorrhage * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Ulna fracture * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Upper limb fracture * 1  3/6276 (0.05%)  3 1/6270 (0.02%)  1
Urinary retention postoperative * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Uveitis-glaucoma-hyphaema syndrome * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Vascular graft occlusion * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Wound complication * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Wrist fracture * 1  1/6276 (0.02%)  1 2/6270 (0.03%)  2
Investigations     
Arteriogram coronary * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Biopsy prostate * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Blood pressure increased * 1  0/6276 (0.00%)  0 2/6270 (0.03%)  2
Electrocardiogram abnormal * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Haemoglobin decreased * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Liver function test abnormal * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Prostatic specific antigen increased * 1  0/6276 (0.00%)  0 2/6270 (0.03%)  2
Serum ferritin increased * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Weight decreased * 1  3/6276 (0.05%)  3 1/6270 (0.02%)  1
White blood cell count increased * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Metabolism and nutrition disorders     
Dehydration * 1  1/6276 (0.02%)  1 4/6270 (0.06%)  4
Diabetes mellitus * 1  1/6276 (0.02%)  2 2/6270 (0.03%)  2
Fluid retention * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Gout * 1  0/6276 (0.00%)  0 2/6270 (0.03%)  2
Hyperkalaemia * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Hypoglycaemia * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Hypokalaemia * 1  0/6276 (0.00%)  0 2/6270 (0.03%)  2
Hyponatraemia * 1  2/6276 (0.03%)  2 1/6270 (0.02%)  1
Lactic acidosis * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Metabolic acidosis * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Obesity * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Type 2 diabetes mellitus * 1  5/6276 (0.08%)  7 8/6270 (0.13%)  8
Musculoskeletal and connective tissue disorders     
Arthralgia * 1  10/6276 (0.16%)  10 3/6270 (0.05%)  3
Arthritis * 1  6/6276 (0.10%)  6 6/6270 (0.10%)  7
Arthropathy * 1  2/6276 (0.03%)  2 2/6270 (0.03%)  2
Back pain * 1  8/6276 (0.13%)  9 6/6270 (0.10%)  6
Bone pain * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Bursitis * 1  3/6276 (0.05%)  3 4/6270 (0.06%)  4
Cervical spinal stenosis * 1  2/6276 (0.03%)  2 1/6270 (0.02%)  1
Dupuytren's contracture * 1  5/6276 (0.08%)  5 3/6270 (0.05%)  3
Exostosis * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Facet joint syndrome * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Foot deformity * 1  2/6276 (0.03%)  4 3/6270 (0.05%)  4
Fracture nonunion * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Gouty arthritis * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Groin pain * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Intervertebral disc compression * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Intervertebral disc degeneration * 1  2/6276 (0.03%)  2 0/6270 (0.00%)  0
Intervertebral disc disorder * 1  1/6276 (0.02%)  1 3/6270 (0.05%)  3
Intervertebral disc protrusion * 1  8/6276 (0.13%)  8 6/6270 (0.10%)  8
Lumbar spinal stenosis * 1  4/6276 (0.06%)  4 3/6270 (0.05%)  4
Meniscal degeneration * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Mixed connective tissue disease * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Muscle haemorrhage * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Musculoskeletal chest pain * 1  1/6276 (0.02%)  1 1/6270 (0.02%)  1
Musculoskeletal pain * 1  2/6276 (0.03%)  2 2/6270 (0.03%)  2
Myalgia * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Neck pain * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Osteitis * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Osteoarthritis * 1  103/6276 (1.64%)  109 104/6270 (1.66%)  114
Osteochondritis * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Osteochondrosis * 1  1/6276 (0.02%)  1 2/6270 (0.03%)  2
Osteoporotic fracture * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Pain in extremity * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Patellofemoral pain syndrome * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Pathological fracture * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Peripheral arthritis * 1  3/6276 (0.05%)  3 2/6270 (0.03%)  2
Polymyalgia rheumatica * 1  0/6276 (0.00%)  0 4/6270 (0.06%)  4
Pseudarthrosis * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Rhabdomyolysis * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Rheumatoid arthritis * 1  2/6276 (0.03%)  3 1/6270 (0.02%)  1
Rotator cuff syndrome * 1  13/6276 (0.21%)  13 6/6270 (0.10%)  6
Scoliosis * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Spinal column stenosis * 1  7/6276 (0.11%)  7 4/6270 (0.06%)  4
Spinal deformity * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Spinal disorder * 1  1/6276 (0.02%)  2 0/6270 (0.00%)  0
Spinal osteoarthritis * 1  2/6276 (0.03%)  2 0/6270 (0.00%)  0
Spinal pain * 1  0/6276 (0.00%)  0 2/6270 (0.03%)  2
Spondylolisthesis * 1  2/6276 (0.03%)  2 2/6270 (0.03%)  2
Synovial cyst * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Synovitis * 1  2/6276 (0.03%)  2 0/6270 (0.00%)  0
Systemic lupus erythematosus * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Vertebral foraminal stenosis * 1  2/6276 (0.03%)  2 0/6270 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Acoustic neuroma * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Adenocarcinoma * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Adenocarcinoma gastric * 1  2/6276 (0.03%)  2 0/6270 (0.00%)  0
Adenocarcinoma of colon * 1  6/6276 (0.10%)  6 6/6270 (0.10%)  6
Adenocarcinoma pancreas * 1  2/6276 (0.03%)  2 1/6270 (0.02%)  1
Adenolymphoma * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Adenoma benign * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Adrenal adenoma * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Adrenal gland cancer metastatic * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Adrenocortical carcinoma * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Ameloblastoma * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Atypical fibroxanthoma * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
B-cell lymphoma * 1  2/6276 (0.03%)  2 1/6270 (0.02%)  1
B-cell lymphoma stage IV * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
B-cell unclassifiable lymphoma high grade * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Basal cell carcinoma * 1  7/6276 (0.11%)  7 2/6270 (0.03%)  2
Basosquamous carcinoma of skin * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Benign anorectal neoplasm * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Benign lung neoplasm * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Benign mediastinal neoplasm * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Benign neoplasm of testis * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Benign neoplasm of thyroid gland * 1  1/6276 (0.02%)  1 1/6270 (0.02%)  1
Benign ovarian tumour * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Benign pancreatic neoplasm * 1  2/6276 (0.03%)  3 0/6270 (0.00%)  0
Benign salivary gland neoplasm * 1  0/6276 (0.00%)  0 2/6270 (0.03%)  2
Bladder cancer * 1  7/6276 (0.11%)  7 6/6270 (0.10%)  6
Bladder neoplasm * 1  1/6276 (0.02%)  1 4/6270 (0.06%)  4
Bladder papilloma * 1  0/6276 (0.00%)  0 3/6270 (0.05%)  3
Bladder transitional cell carcinoma * 1  10/6276 (0.16%)  12 9/6270 (0.14%)  10
Bladder transitional cell carcinoma metastatic * 1  0/6276 (0.00%)  0 2/6270 (0.03%)  2
Bladder transitional cell carcinoma recurrent * 1  1/6276 (0.02%)  1 3/6270 (0.05%)  3
Bladder transitional cell carcinoma stage I * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Bowen's disease * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Brain cancer metastatic * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Brain neoplasm * 1  2/6276 (0.03%)  2 1/6270 (0.02%)  1
Brain neoplasm malignant * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Breast cancer * 1  7/6276 (0.11%)  7 10/6270 (0.16%)  10
Breast cancer metastatic * 1  2/6276 (0.03%)  2 4/6270 (0.06%)  4
Breast neoplasm * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Bronchial carcinoma * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Carcinoid tumour of the caecum * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Central nervous system lymphoma * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Cervix carcinoma * 1  1/6276 (0.02%)  1 1/6270 (0.02%)  1
Chondroma * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Choroid melanoma * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Chronic lymphocytic leukaemia * 1  4/6276 (0.06%)  5 4/6270 (0.06%)  5
Clear cell renal cell carcinoma * 1  1/6276 (0.02%)  1 2/6270 (0.03%)  2
Colon adenoma * 1  5/6276 (0.08%)  6 2/6270 (0.03%)  2
Colon cancer * 1  6/6276 (0.10%)  6 14/6270 (0.22%)  14
Colon cancer metastatic * 1  1/6276 (0.02%)  1 4/6270 (0.06%)  4
Colon neoplasm * 1  1/6276 (0.02%)  1 1/6270 (0.02%)  1
Colorectal cancer * 1  1/6276 (0.02%)  1 1/6270 (0.02%)  1
Colorectal cancer metastatic * 1  2/6276 (0.03%)  2 0/6270 (0.00%)  0
Diffuse large B-cell lymphoma stage III * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Endometrial adenocarcinoma * 1  0/6276 (0.00%)  0 2/6270 (0.03%)  2
Extraskeletal myxoid chondrosarcoma * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Fibroma * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Gastric cancer * 1  1/6276 (0.02%)  2 3/6270 (0.05%)  3
Gastrointestinal cancer metastatic * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Gastrointestinal carcinoma * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Gastrointestinal neoplasm * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Gastrointestinal stromal cancer * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Gastrointestinal stromal tumour * 1  1/6276 (0.02%)  1 1/6270 (0.02%)  1
Gastrointestinal tract adenoma * 1  2/6276 (0.03%)  2 0/6270 (0.00%)  0
Glottis carcinoma * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Haemangioma * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Hepatic cancer * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Hepatic cancer metastatic * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Hepatocellular carcinoma * 1  1/6276 (0.02%)  1 1/6270 (0.02%)  1
Hodgkin's disease * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Insulinoma * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Intracranial haemangioma * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Intraocular melanoma * 1  1/6276 (0.02%)  1 1/6270 (0.02%)  1
Invasive breast carcinoma * 1  2/6276 (0.03%)  2 1/6270 (0.02%)  1
Invasive ductal breast carcinoma * 1  1/6276 (0.02%)  1 5/6270 (0.08%)  5
Laryngeal cancer * 1  1/6276 (0.02%)  1 2/6270 (0.03%)  2
Laryngeal cancer metastatic * 1  2/6276 (0.03%)  2 1/6270 (0.02%)  1
Laryngeal squamous cell carcinoma * 1  2/6276 (0.03%)  2 0/6270 (0.00%)  0
Leiomyoma * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Lentigo maligna * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Lentigo maligna recurrent * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Lip squamous cell carcinoma * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Lipoma * 1  0/6276 (0.00%)  0 2/6270 (0.03%)  2
Liposarcoma * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Lung adenocarcinoma * 1  2/6276 (0.03%)  2 2/6270 (0.03%)  2
Lung adenocarcinoma metastatic * 1  1/6276 (0.02%)  1 1/6270 (0.02%)  1
Lung adenocarcinoma stage I * 1  1/6276 (0.02%)  1 0/6270 (0.00%)  0
Lung cancer metastatic * 1  0/6276 (0.00%)  0 4/6270 (0.06%)  4
Lung carcinoma cell type unspecified recurrent * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Lung neoplasm * 1  1/6276 (0.02%)  1 1/6270 (0.02%)  1
Lung neoplasm malignant * 1  3/6276 (0.05%)  3 10/6270 (0.16%)  10
Lung squamous cell carcinoma metastatic * 1  0/6276 (0.00%)  0 1/6270 (0.02%)  1
Lymphangiosis carcinomatosa * 1  0/6276 (0.00%)  0