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Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk (FOURIER)

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ClinicalTrials.gov Identifier: NCT01764633
Recruitment Status : Completed
First Posted : January 9, 2013
Results First Posted : February 15, 2018
Last Update Posted : August 21, 2019
Sponsor:
Information provided by (Responsible Party):
Amgen

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Dyslipidemia
Interventions Biological: Evolocumab
Drug: Placebo
Enrollment 27564
Recruitment Details Participants were enrolled at 1242 clinical centers in 49 countries in the regions of Europe (62.9%), North America (16.6%), Asia Pacific (13.9%), and Latin America (6.6%) from 08 February 2013 to 05 June 2015.
Pre-assignment Details Eligible participants were randomized in a 1:1 ratio to receive either subcutaneous (SC) evolocumab or placebo. Randomization was stratified by the final screening low-density lipoprotein cholesterol (LDL-C) level (< 85 mg/dL vs ≥ 85 mg/dL) and by geographical region.
Arm/Group Title Placebo Evolocumab
Hide Arm/Group Description Participants received placebo subcutaneous injections either once every 2 weeks (Q2W) or once a month (QM) according to their own preference. Participants received evolocumab subcutaneous injections either 140 mg Q2W or 420 mg QM according to their own preference.
Period Title: Overall Study
Started 13780 13784
Received Treatment 13756 13769
Completed 13662 13691
Not Completed 118 93
Reason Not Completed
Withdrawal by Subject             105             88
Lost to Follow-up             13             5
Arm/Group Title Placebo Evolocumab Total
Hide Arm/Group Description Participants received placebo subcutaneous injections either once every 2 weeks (Q2W) or once a month (QM) according to their own preference. Participants received evolocumab subcutaneous injections either 140 mg Q2W or 420 mg QM according to their own preference. Total of all reporting groups
Overall Number of Baseline Participants 13780 13784 27564
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 13780 participants 13784 participants 27564 participants
62.5  (8.9) 62.5  (9.1) 62.5  (9.0)
Age, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 13780 participants 13784 participants 27564 participants
< 65 years
7687
  55.8%
7623
  55.3%
15310
  55.5%
≥ 65 years
6093
  44.2%
6161
  44.7%
12254
  44.5%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 13780 participants 13784 participants 27564 participants
Female
3382
  24.5%
3387
  24.6%
6769
  24.6%
Male
10398
  75.5%
10397
  75.4%
20795
  75.4%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 13780 participants 13784 participants 27564 participants
Hispanic or Latino
1084
   7.9%
1093
   7.9%
2177
   7.9%
Not Hispanic or Latino
12694
  92.1%
12688
  92.0%
25382
  92.1%
Unknown or Not Reported
2
   0.0%
3
   0.0%
5
   0.0%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 13780 participants 13784 participants 27564 participants
American Indian or Alaska Native
80
   0.6%
60
   0.4%
140
   0.5%
Asian
1349
   9.8%
1374
  10.0%
2723
   9.9%
Black or African American
352
   2.6%
317
   2.3%
669
   2.4%
Native Hawaiian or Other Pacific Islander
11
   0.1%
15
   0.1%
26
   0.1%
White
11710
  85.0%
11748
  85.2%
23458
  85.1%
Multiple
12
   0.1%
19
   0.1%
31
   0.1%
Other
266
   1.9%
251
   1.8%
517
   1.9%
Low-density Lipoprotein Cholesterol  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 13780 participants 13784 participants 27564 participants
< 85 mg/dL
4803
  34.9%
4809
  34.9%
9612
  34.9%
≥ 85 mg/dL
8977
  65.1%
8975
  65.1%
17952
  65.1%
Geographical Region  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 13780 participants 13784 participants 27564 participants
Europe
8669
  62.9%
8667
  62.9%
17336
  62.9%
North America
2284
  16.6%
2286
  16.6%
4570
  16.6%
Latin America
910
   6.6%
913
   6.6%
1823
   6.6%
Asia Pacific
1917
  13.9%
1918
  13.9%
3835
  13.9%
1.Primary Outcome
Title Time to Cardiovascular Death, Myocardial Infarction, Hospitalization for Unstable Angina, Stroke, or Coronary Revascularization
Hide Description

All deaths and potential endpoint events were adjudicated by an independent external Clinical Events Committee (CEC) led by the Thrombolysis in Myocardial Infarction (TIMI) Study Group, using standardized definitions based on the “Standardized Definitions for Cardiovascular and Stroke End Point Events in Clinical Trials and the Third Universal Definition of Myocardial Infarction”.

Time to cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization was defined as the time from randomization to the first occurrence of any component of the composite endpoint and was analyzed using Kaplan-Meier (KM) survival analysis. KM estimates of the percentage of participants with an event are reported. Participants with no event were censored based on last non-fatal potential endpoint collection date.

Time Frame Events that occurred from randomization to the last confirmed survival status date; the median duration of follow-up was 26 months. KM estimates at 6, 12, 18, 24, 30 and 36 months are reported.
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants; The number of participants entered at each time point represents the number of participants at risk.
Arm/Group Title Placebo Evolocumab
Hide Arm/Group Description:
Participants received placebo subcutaneous injections either once every 2 weeks (Q2W) or once a month (QM) according to their own preference.
Participants received evolocumab subcutaneous injections either 140 mg Q2W or 420 mg QM according to their own preference.
Overall Number of Participants Analyzed 13780 13784
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
KM estimate at 6 months Number Analyzed 13276 participants 13349 participants
3.11
(2.82 to 3.40)
2.74
(2.47 to 3.01)
KM estimate at 12 months Number Analyzed 12822 participants 12937 participants
6.01
(5.61 to 6.41)
5.31
(4.93 to 5.68)
KM estimate at 18 months Number Analyzed 11837 participants 12034 participants
8.32
(7.86 to 8.78)
7.25
(6.81 to 7.68)
KM estimate at 24 months Number Analyzed 7589 participants 7743 participants
10.66
(10.12 to 11.19)
9.13
(8.63 to 9.63)
KM estimate at 30 months Number Analyzed 3589 participants 3652 participants
12.72
(12.08 to 13.35)
10.91
(10.31 to 11.50)
KM estimate at 36 months Number Analyzed 672 participants 681 participants
14.64
(13.76 to 15.50)
12.57
(11.70 to 13.42)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Evolocumab
Comments The primary endpoint was compared between treatment groups at a significance level of 0.05.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Log Rank
Comments Two-sided log-rank test stratified by randomization stratification factors (final screening LDL-C level and region).
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.85
Confidence Interval (2-Sided) 95%
0.79 to 0.92
Estimation Comments Based on a Cox model stratified by the randomization stratification factors.
2.Secondary Outcome
Title Time to Cardiovascular Death, Myocardial Infarction, or Stroke
Hide Description All deaths and potential endpoint events were adjudicated by an independent external CEC led by the TIMI Study Group, using standardized definitions based on the “Standardized Definitions for Cardiovascular and Stroke End Point Events in Clinical Trials and the Third Universal Definition of Myocardial Infarction”. Time to cardiovascular death, myocardial infarction, or stroke was defined as the time from randomization to the first occurrence of any component of the composite endpoint and was analyzed using Kaplan-Meier (KM) survival analysis. KM estimates of the percentage of participants with an event are reported. Participants with no event were censored based on last non-fatal potential endpoint collection date.
Time Frame Events that occurred from randomization to the last confirmed survival status date; the median duration of follow-up was 26 months. KM estimates at 6, 12, 18, 24, 30 and 36 months are reported.
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants; The number of participants entered at each time point represents the number of participants at risk.
Arm/Group Title Placebo Evolocumab
Hide Arm/Group Description:
Participants received placebo subcutaneous injections either once every 2 weeks (Q2W) or once a month (QM) according to their own preference.
Participants received evolocumab subcutaneous injections either 140 mg Q2W or 420 mg QM according to their own preference.
Overall Number of Participants Analyzed 13780 13784
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
KM estimate at 6 months Number Analyzed 13447 participants 13499 participants
1.86
(1.63 to 2.08)
1.65
(1.44 to 1.86)
KM estimate at 12 months Number Analyzed 13140 participants 13240 participants
3.68
(3.36 to 3.99)
3.10
(2.81 to 3.38)
KM estimate at 18 months Number Analyzed 12257 participants 12422 participants
5.18
(4.81 to 5.55)
4.29
(3.95 to 4.62)
KM estimate at 24 months Number Analyzed 7923 participants 8066 participants
6.83
(6.39 to 7.26)
5.47
(5.08 to 5.86)
KM estimate at 30 months Number Analyzed 3785 participants 3837 participants
8.31
(7.78 to 8.84)
6.66
(6.19 to 7.14)
KM estimate at 36 months Number Analyzed 717 participants 713 participants
9.93
(9.16 to 10.69)
7.90
(7.17 to 8.63)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Evolocumab
Comments If the primary endpoint reached statistical significance at the 0.05 level, the key secondary endpoint (composite of cardiovascular death, myocardial infarction, and stroke) was tested at a significance level of 0.05.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Log Rank
Comments Two-sided log-rank test stratified by randomization stratification factors (final screening LDL-C level and region).
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.80
Confidence Interval (2-Sided) 95%
0.73 to 0.88
Estimation Comments Based on a Cox model stratified by the randomization stratification factors.
3.Secondary Outcome
Title Time to Cardiovascular Death
Hide Description

All deaths and potential endpoint events were adjudicated by an independent external CEC led by the TIMI Study Group, using standardized definitions based on the “Standardized Definitions for Cardiovascular and Stroke End Point Events in Clinical Trials and the Third Universal Definition of Myocardial Infarction”.

Cardiovascular death includes death resulting from an acute myocardial infarction (MI), sudden cardiac death, death due to heart failure (HF), death due to stroke, death due to cardiovascular (CV) procedures, death due to CV hemorrhage, and death due to other CV causes.

Time to cardiovascular death was defined as the time from randomization to the date of cardiovascular death and was analyzed using Kaplan-Meier (KM) survival analysis. KM estimates of the percentage of participants with an event are reported. Participants with no event were censored based on the last confirmed survival status date.

Time Frame Events that occurred from randomization to the last confirmed survival status date; the median duration of follow-up was 26 months. KM estimates at 6, 12, 18, 24, 30 and 36 months are reported.
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants; The number of participants entered at each time point represents the number of participants at risk.
Arm/Group Title Placebo Evolocumab
Hide Arm/Group Description:
Participants received placebo subcutaneous injections either once every 2 weeks (Q2W) or once a month (QM) according to their own preference.
Participants received evolocumab subcutaneous injections either 140 mg Q2W or 420 mg QM according to their own preference.
Overall Number of Participants Analyzed 13780 13784
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
KM estimate at 6 months Number Analyzed 13688 participants 13698 participants
0.40
(0.29 to 0.50)
0.39
(0.29 to 0.50)
KM estimate at 12 months Number Analyzed 13590 participants 13598 participants
0.82
(0.67 to 0.97)
0.79
(0.64 to 0.94)
KM estimate at 18 months Number Analyzed 12844 participants 12869 participants
1.19
(1.01 to 1.37)
1.20
(1.01 to 1.38)
KM estimate at 24 months Number Analyzed 8427 participants 8441 participants
1.57
(1.36 to 1.79)
1.64
(1.42 to 1.85)
KM estimate at 30 months Number Analyzed 4081 participants 4043 participants
1.99
(1.72 to 2.26)
2.11
(1.83 to 2.39)
KM estimate at 36 months Number Analyzed 783 participants 767 participants
2.39
(1.98 to 2.80)
2.49
(2.09 to 2.88)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Evolocumab
Comments If the primary and key secondary endpoints reached a statistical significance level of 0.05, then the endpoint of cardiovascular death was tested at a significance level of 0.05.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6188
Comments [Not Specified]
Method Log Rank
Comments Two-sided log-rank test stratified by randomization stratification factors (final screening LDL-C level and region).
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.05
Confidence Interval (2-Sided) 95%
0.88 to 1.25
Estimation Comments Based on a Cox model stratified by the randomization stratification factors.
4.Secondary Outcome
Title Time to All Cause Death
Hide Description Time to all-cause death was defined as the time from randomization to the date of death and was analyzed using Kaplan-Meier (KM) survival analysis. KM estimates of the percentage of participants with an event are reported. Participants with no event were censored based on the last confirmed survival status date.
Time Frame Events that occurred from randomization to the last confirmed survival status date; the median duration of follow-up was 26 months. KM estimates at 6, 12, 18, 24, 30 and 36 months are reported.
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants; The number of participants entered at each time point represents the number of participants at risk.
Arm/Group Title Placebo Evolocumab
Hide Arm/Group Description:
Participants received placebo subcutaneous injections either once every 2 weeks (Q2W) or once a month (QM) according to their own preference.
Participants received evolocumab subcutaneous injections either 140 mg Q2W or 420 mg QM according to their own preference.
Overall Number of Participants Analyzed 13780 13784
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
KM estimate at 6 months Number Analyzed 13688 participants 13698 participants
0.62
(0.49 to 0.75)
0.55
(0.43 to 0.68)
KM estimate at 12 months Number Analyzed 13590 participants 13598 participants
1.29
(1.10 to 1.47)
1.26
(1.07 to 1.44)
KM estimate at 18 months Number Analyzed 12844 participants 12869 participants
1.96
(1.73 to 2.19)
1.94
(1.71 to 2.17)
KM estimate at 24 months Number Analyzed 8427 participants 8441 participants
2.78
(2.49 to 3.06)
2.81
(2.52 to 3.10)
KM estimate at 30 months Number Analyzed 4081 participants 4043 participants
3.48
(3.12 to 3.83)
3.63
(3.27 to 3.98)
KM estimate at 36 months Number Analyzed 783 participants 767 participants
4.28
(3.74 to 4.82)
4.75
(4.16 to 5.34)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Evolocumab
Comments If the primary, key secondary, and endpoint cardiovascular death reached a statistical significance level of 0.05, then the endpoint of all-cause death was tested at a significance level of 0.04 and remaining secondary endpoints at an overall significant level of 0.01 by applying the Hochberg method.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5368
Comments [Not Specified]
Method Log Rank
Comments Two-sided log-rank test stratified by randomization stratification factors (final screening LDL-C level and region).
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.04
Confidence Interval (2-Sided) 95%
0.91 to 1.19
Estimation Comments Based on a Cox model stratified by the randomization stratification factors.
5.Secondary Outcome
Title Time to First Myocardial Infarction
Hide Description

All deaths and potential endpoint events were adjudicated by an independent external CEC led by the TIMI Study Group, using standardized definitions based on the “Standardized Definitions for Cardiovascular and Stroke End Point Events in Clinical Trials and the Third Universal Definition of Myocardial Infarction”.

The diagnosis of myocardial infarction required the combination of:

  • Evidence of myocardial necrosis (either changes in cardiac biomarkers or post-mortem pathological findings); and
  • Supporting information derived from the clinical presentation, electrocardiographic changes, or the results of myocardial or coronary artery Imaging.

Time to first myocardial infarction was defined as the time from randomization to the date of the first MI and was analyzed using Kaplan-Meier survival analysis. KM estimates of the percentage of participants with an event are reported. Participants with no event were censored based on last non-fatal potential endpoint collection date.

Time Frame Events that occurred from randomization to the last confirmed survival status date; the median duration of follow-up was 26 months. KM estimates at 6, 12, 18, 24, 30 and 36 months are reported.
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants; The number of participants entered at each time point represents the number of participants at risk.
Arm/Group Title Placebo Evolocumab
Hide Arm/Group Description:
Participants received placebo subcutaneous injections either once every 2 weeks (Q2W) or once a month (QM) according to their own preference.
Participants received evolocumab subcutaneous injections either 140 mg Q2W or 420 mg QM according to their own preference.
Overall Number of Participants Analyzed 13780 13784
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
KM estimate at 6 months Number Analyzed 13497 participants 13536 participants
1.14
(0.97 to 1.32)
1.06
(0.88 to 1.23)
KM estimate at 12 months Number Analyzed 13226 participants 13312 participants
2.39
(2.13 to 2.64)
1.90
(1.67 to 2.13)
KM estimate at 18 months Number Analyzed 12374 participants 12522 participants
3.33
(3.03 to 3.63)
2.55
(2.28 to 2.81)
KM estimate at 24 months Number Analyzed 8031 participants 8137 participants
4.30
(3.95 to 4.65)
3.21
(2.90 to 3.51)
KM estimate at 30 months Number Analyzed 3839 participants 3883 participants
5.25
(4.82 to 5.67)
3.83
(3.47 to 4.19)
KM estimate at 36 months Number Analyzed 733 participants 726 participants
6.28
(5.67 to 6.89)
4.41
(3.85 to 4.96)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Evolocumab
Comments If the primary, key secondary, and endpoint of cardiovascular death reached a statistical significance level of 0.05, then the endpoint of all-cause death was tested at a significance level of 0.04 and remaining secondary endpoints were tested at an overall significance level of 0.01 by applying the Hochberg method.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Log Rank
Comments Two-sided log-rank test stratified by randomization stratification factors (final screening LDL-C level and region).
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.73
Confidence Interval (2-Sided) 95%
0.65 to 0.82
Estimation Comments Based on a Cox model stratified by the randomization stratification factors.
6.Secondary Outcome
Title Time to First Stroke
Hide Description

All deaths and potential endpoint events were adjudicated by an independent external CEC led by the TIMI Study Group, using standardized definitions based on the “Standardized Definitions for Cardiovascular and Stroke End Point Events in Clinical Trials and the Third Universal Definition of Myocardial Infarction”.

Stroke was defined as an acute episode of focal or global neurological dysfunction caused by brain, spinal cord, or retinal vascular injury as a result of hemorrhage or infarction.

Time to first stroke was defined as the time from randomization to the date of the stroke and was analyzed using Kaplan-Meier (KM) survival analysis. KM estimates of the percentage of participants with an event are reported. Participants with no event were censored based on last non-fatal potential endpoint collection date.

Time Frame Events that occurred from randomization to the last confirmed survival status date; the median duration of follow-up was 26 months. KM estimates at 6, 12, 18, 24, 30 and 36 months are reported.
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants; The number of participants entered at each time point represents the number of participants at risk.
Arm/Group Title Placebo Evolocumab
Hide Arm/Group Description:
Participants received placebo subcutaneous injections either once every 2 weeks (Q2W) or once a month (QM) according to their own preference.
Participants received evolocumab subcutaneous injections either 140 mg Q2W or 420 mg QM according to their own preference.
Overall Number of Participants Analyzed 13780 13784
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
KM estimate at 6 months Number Analyzed 13587 participants 13631 participants
0.50
(0.38 to 0.61)
0.31
(0.22 to 0.41)
KM estimate at 12 months Number Analyzed 13428 participants 13470 participants
0.85
(0.69 to 1.00)
0.70
(0.56 to 0.84)
KM estimate at 18 months Number Analyzed 12626 participants 12703 participants
1.30
(1.11 to 1.50)
1.05
(0.88 to 1.22)
KM estimate at 24 months Number Analyzed 8240 participants 8304 participants
1.80
(1.57 to 2.04)
1.36
(1.16 to 1.56)
KM estimate at 30 months Number Analyzed 3977 participants 3967 participants
2.15
(1.88 to 2.43)
1.71
(1.46 to 1.96)
KM estimate at 36 months Number Analyzed 757 participants 741 participants
2.60
(2.20 to 3.00)
2.18
(1.76 to 2.59)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Evolocumab
Comments If the primary, key secondary, and endpoint of cardiovascular death reached a statistical significance level of 0.05, then the endpoint of all-cause death was tested at a significance level of 0.04 and remaining secondary endpoints were tested at an overall significance level of 0.01 by applying the Hochberg method.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0101
Comments [Not Specified]
Method Log Rank
Comments Two-sided log-rank test stratified by randomization stratification factors (final screening LDL-C level and region).
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.79
Confidence Interval (2-Sided) 95%
0.66 to 0.95
Estimation Comments Based on a Cox model stratified by the randomization stratification factors.
7.Secondary Outcome
Title Time to First Coronary Revascularization
Hide Description

All deaths and potential endpoint events were adjudicated by an independent external CEC led by the TIMI Study Group, using standardized definitions based on the “Standardized Definitions for Cardiovascular and Stroke End Point Events in Clinical Trials and the Third Universal Definition of Myocardial Infarction”.

Time to first coronary revascularization was defined as the time from randomization to the date of the coronary revascularization and was analyzed using Kaplan-Meier (KM) survival analysis. KM estimates of the percentage of participants with an event are reported. Participants with no event were censored based on last non-fatal potential endpoint collection date.

Time Frame Events that occurred from randomization to the last confirmed survival status date; the median duration of follow-up was 26 months. KM estimates at 6, 12, 18, 24, 30 and 36 months are reported.
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants; the number of participants entered at each time point represents the number of participants at risk.
Arm/Group Title Placebo Evolocumab
Hide Arm/Group Description:
Participants received placebo subcutaneous injections either once every 2 weeks (Q2W) or once a month (QM) according to their own preference.
Participants received evolocumab subcutaneous injections either 140 mg Q2W or 420 mg QM according to their own preference.
Overall Number of Participants Analyzed 13780 13784
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
KM estimate at 6 months Number Analyzed 13390 participants 13454 participants
1.87
(1.65 to 2.10)
1.60
(1.39 to 1.81)
KM estimate at 12 months Number Analyzed 13029 participants 13130 participants
3.71
(3.39 to 4.02)
3.13
(2.84 to 3.42)
KM estimate at 18 months Number Analyzed 12097 participants 12283 participants
5.20
(4.82 to 5.57)
4.16
(3.83 to 4.50)
KM estimate at 24 months Number Analyzed 7812 participants 7952 participants
6.57
(6.14 to 7.00)
5.22
(4.84 to 5.61)
KM estimate at 30 months Number Analyzed 3718 participants 3768 participants
7.91
(7.39 to 8.42)
6.13
(5.68 to 6.58)
KM estimate at 36 months Number Analyzed 704 participants 710 participants
9.17
(8.46 to 9.87)
7.01
(6.36 to 7.65)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Evolocumab
Comments If the primary, key secondary, and endpoint of cardiovascular death reached a statistical significance level of 0.05, then the endpoint of all-cause death was tested at a significance level of 0.04 and remaining secondary endpoints were tested at an overall significance level of 0.01 by applying the Hochberg method.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Log Rank
Comments Two-sided log-rank test stratified by randomization stratification factors (final screening LDL-C level and region).
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.78
Confidence Interval (2-Sided) 95%
0.71 to 0.86
Estimation Comments Based on a Cox model stratified by the randomization stratification factors.
8.Secondary Outcome
Title Time to Cardiovascular Death or First Hospitalization for Worsening Heart Failure
Hide Description

All events were adjudicated by an independent external CEC led by the TIMI Study Group, using standardized definitions.

HF hospitalization was defined as an event that met all of the following criteria:

  1. Admitted to hospital with a primary diagnosis of HF
  2. In hospital for at least 24 hours
  3. Documented new or worsening symptoms due to HF, including at least 1 of the following:

    • Dyspnea
    • Decreased exercise tolerance
    • Fatigue
    • Other symptoms of worsened end-organ perfusion or volume overload
  4. Evidence of new or worsening HF consisting of at least 2 physical exam findings or 1 physical exam finding and at least 1 laboratory criterion
  5. Received new or increased treatment for HF. Time to CV death or first hospitalization for worsening HF was defined as the time from randomization to the first occurrence of any component of the endpoint analyzed using KM survival analysis. Participants with no event were censored based on last non-fatal potential endpoint collection date.
Time Frame Events that occurred from randomization to the last confirmed survival status date; the median duration of follow-up was 26 months. KM estimates at 6, 12, 18, 24, 30 and 36 months are reported.
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Hide Analysis Population Description
All randomized participants; the number of participants entered at each time point represents the number of participants at risk.
Arm/Group Title Placebo Evolocumab
Hide Arm/Group Description:
Participants received placebo subcutaneous injections either once every 2 weeks (Q2W) or once a month (QM) according to their own preference.
Participants received evolocumab subcutaneous injections either 140 mg Q2W or 420 mg QM according to their own preference.
Overall Number of Participants Analyzed 13780 13784
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
KM estimate at 6 months Number Analyzed 13592 participants 13635 participants
0.79
(0.64 to 0.93)
0.64
(0.51 to 0.77)
KM estimate at 12 months Number Analyzed 13455 participants 13481 participants
1.35
(1.16 to 1.54)
1.29
(1.10 to 1.48)
KM estimate at 18 months Number Analyzed 12664 participants 12710 participants
1.99
(1.75 to 2.22)
1.99
(1.76 to 2.22)
KM estimate at 24 months Number Analyzed 8265 participants 8304 participants
2.70
(2.41 to 2.98)
2.64
(2.36 to 2.92)
KM estimate at 30 months Number Analyzed 3983 participants 3967 participants
3.45
(3.09 to 3.81)
3.31
(2.97 to 3.65)
KM estimate at 36 months Number Analyzed 761 participants 737 participants
4.03
(3.50 to 4.55)
4.13
(3.57 to 4.68)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Evolocumab
Comments If the primary, key secondary, and endpoint of cardiovascular death reached a statistical significance level of 0.05, then the endpoint of all-cause death was tested at a significance level of 0.04 and remaining secondary endpoints were tested at an overall significance level of 0.01 by applying the Hochberg method.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8179
Comments [Not Specified]
Method Log Rank
Comments Two-sided log-rank test stratified by randomization stratification factors (final screening LDL-C level and region).
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.98
Confidence Interval (2-Sided) 95%
0.86 to 1.13
Estimation Comments Based on a Cox model stratified by the randomization stratification factors.
9.Secondary Outcome
Title Time to First Ischemic Fatal or Non-Fatal Stroke or Transient Ischemic Attack
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All deaths and potential endpoint events were adjudicated by an independent external CEC led by the TIMI Study Group, using standardized definitions.

Ischemic stroke was defined as an acute episode of focal cerebral, spinal, or retinal dysfunction caused by infarction of central nervous system tissue. Transient ischemic attack (TIA) was defined as a transient episode of focal neurological dysfunction caused by brain, spinal cord, or retinal ischemia, without acute infarction.

Time to first ischemic fatal or non-fatal stroke or TIA was defined as the time from randomization to the first occurrence of any component of the composite endpoint and was analyzed using KM analysis. KM estimates of the percentage of participants with an event are reported. Participants with no event were censored based on last non-fatal potential endpoint collection date.

Time Frame Events that occurred from randomization to the last confirmed survival status date; the median duration of follow-up was 26 months. KM estimates at 6, 12, 18, 24, 30 and 36 months are reported.
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants; the number of participants entered at each time point represents the number of participants at risk.
Arm/Group Title Placebo Evolocumab
Hide Arm/Group Description:
Participants received placebo subcutaneous injections either once every 2 weeks (Q2W) or once a month (QM) according to their own preference.
Participants received evolocumab subcutaneous injections either 140 mg Q2W or 420 mg QM according to their own preference.
Overall Number of Participants Analyzed 13780 13784
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
KM estimate at 6 months Number Analyzed 13569 participants 13614 participants
0.61
(0.48 to 0.73)
0.42
(0.31 to 0.53)
KM estimate at 12 months Number Analyzed 13394 participants 13445 participants
1.05
(0.88 to 1.22)
0.83
(0.67 to 0.98)
KM estimate at 18 months Number Analyzed 12588 participants 12671 participants
1.52
(1.32 to 1.73)
1.18
(1.00 to 1.37)
KM estimate at 24 months Number Analyzed 8209 participants 8279 participants
2.05
(1.81 to 2.30)
1.46
(1.25 to 1.66)
KM estimate at 30 months Number Analyzed 3958 participants 3954 participants
2.40
(2.11 to 2.68)
1.92
(1.65 to 2.19)
KM estimate at 36 months Number Analyzed 756 participants 738 participants
2.81
(2.41 to 3.21)
2.48
(2.01 to 2.95)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Evolocumab
Comments If the primary, key secondary, and endpoint of cardiovascular death reached a statistical significance level of 0.05, then the endpoint of all-cause death was tested at a significance level of 0.04 and remaining secondary endpoints were tested at an overall significance level of 0.01 by applying the Hochberg method.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0035
Comments [Not Specified]
Method Log Rank
Comments Two-sided log-rank test stratified by randomization stratification factors (final screening LDL-C level and region).
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.77
Confidence Interval (2-Sided) 95%
0.65 to 0.92
Estimation Comments Based on a Cox model stratified by the randomization stratification factors.
Time Frame From the first dose of study drug to the end of study. The median duration of follow-up was 26 months.
Adverse Event Reporting Description Deaths by any cause were adjudicated efficacy endpoints in this study and were summarized as a secondary endpoint. Events that were negatively adjudicated (did not meet the definitions of an endpoint), were reclassified as an adverse event or serious adverse event Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
 
Arm/Group Title Placebo Evolocumab
Hide Arm/Group Description Participants received placebo subcutaneous injections either once every 2 weeks (Q2W) or once a month (QM) according to their own preference. Participants received evolocumab subcutaneous injections either 140 mg Q2W or 420 mg QM according to their own preference.
All-Cause Mortality
Placebo Evolocumab
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Placebo Evolocumab
Affected / at Risk (%) Affected / at Risk (%)
Total   3404/13756 (24.75%)   3410/13769 (24.77%) 
Blood and lymphatic system disorders     
Anaemia  1  27/13756 (0.20%)  27/13769 (0.20%) 
Anaemia of chronic disease  1  1/13756 (0.01%)  0/13769 (0.00%) 
Autoimmune haemolytic anaemia  1  1/13756 (0.01%)  0/13769 (0.00%) 
Coagulopathy  1  2/13756 (0.01%)  2/13769 (0.01%) 
Febrile neutropenia  1  2/13756 (0.01%)  3/13769 (0.02%) 
Haemorrhagic anaemia  1  5/13756 (0.04%)  2/13769 (0.01%) 
Haemorrhagic disorder  1  1/13756 (0.01%)  0/13769 (0.00%) 
Hypochromic anaemia  1  1/13756 (0.01%)  2/13769 (0.01%) 
Immune thrombocytopenic purpura  1  1/13756 (0.01%)  2/13769 (0.01%) 
Iron deficiency anaemia  1  6/13756 (0.04%)  9/13769 (0.07%) 
Leukocytosis  1  4/13756 (0.03%)  2/13769 (0.01%) 
Lymphadenitis  1  1/13756 (0.01%)  0/13769 (0.00%) 
Lymphadenopathy  1  3/13756 (0.02%)  2/13769 (0.01%) 
Lymphadenopathy mediastinal  1  2/13756 (0.01%)  0/13769 (0.00%) 
Microcytic anaemia  1  1/13756 (0.01%)  0/13769 (0.00%) 
Neutropenia  1  0/13756 (0.00%)  1/13769 (0.01%) 
Normochromic normocytic anaemia  1  0/13756 (0.00%)  4/13769 (0.03%) 
Pancytopenia  1  0/13756 (0.00%)  1/13769 (0.01%) 
Pernicious anaemia  1  0/13756 (0.00%)  1/13769 (0.01%) 
Polycythaemia  1  0/13756 (0.00%)  2/13769 (0.01%) 
Spleen disorder  1  1/13756 (0.01%)  0/13769 (0.00%) 
Thrombocytopenia  1  1/13756 (0.01%)  0/13769 (0.00%) 
Cardiac disorders     
Acute coronary syndrome  1  11/13756 (0.08%)  6/13769 (0.04%) 
Acute left ventricular failure  1  2/13756 (0.01%)  0/13769 (0.00%) 
Acute myocardial infarction  1  23/13756 (0.17%)  11/13769 (0.08%) 
Angina pectoris  1  221/13756 (1.61%)  208/13769 (1.51%) 
Angina unstable  1  278/13756 (2.02%)  233/13769 (1.69%) 
Aortic valve disease  1  1/13756 (0.01%)  2/13769 (0.01%) 
Aortic valve incompetence  1  2/13756 (0.01%)  2/13769 (0.01%) 
Aortic valve stenosis  1  8/13756 (0.06%)  10/13769 (0.07%) 
Arrhythmia  1  4/13756 (0.03%)  1/13769 (0.01%) 
Arrhythmia supraventricular  1  1/13756 (0.01%)  3/13769 (0.02%) 
Arteriosclerosis coronary artery  1  1/13756 (0.01%)  3/13769 (0.02%) 
Arteritis coronary  1  1/13756 (0.01%)  0/13769 (0.00%) 
Atrial fibrillation  1  132/13756 (0.96%)  119/13769 (0.86%) 
Atrial flutter  1  17/13756 (0.12%)  25/13769 (0.18%) 
Atrial tachycardia  1  2/13756 (0.01%)  2/13769 (0.01%) 
Atrial thrombosis  1  0/13756 (0.00%)  1/13769 (0.01%) 
Atrioventricular block  1  5/13756 (0.04%)  4/13769 (0.03%) 
Atrioventricular block complete  1  13/13756 (0.09%)  16/13769 (0.12%) 
Atrioventricular block first degree  1  3/13756 (0.02%)  1/13769 (0.01%) 
Atrioventricular block second degree  1  7/13756 (0.05%)  7/13769 (0.05%) 
Bifascicular block  1  1/13756 (0.01%)  0/13769 (0.00%) 
Bradyarrhythmia  1  2/13756 (0.01%)  2/13769 (0.01%) 
Bradycardia  1  13/13756 (0.09%)  10/13769 (0.07%) 
Bundle branch block bilateral  1  1/13756 (0.01%)  0/13769 (0.00%) 
Bundle branch block left  1  0/13756 (0.00%)  3/13769 (0.02%) 
Bundle branch block right  1  0/13756 (0.00%)  1/13769 (0.01%) 
Cardiac aneurysm  1  1/13756 (0.01%)  0/13769 (0.00%) 
Cardiac arrest  1  5/13756 (0.04%)  3/13769 (0.02%) 
Cardiac asthma  1  0/13756 (0.00%)  1/13769 (0.01%) 
Cardiac disorder  1  1/13756 (0.01%)  0/13769 (0.00%) 
Cardiac failure  1  66/13756 (0.48%)  66/13769 (0.48%) 
Cardiac failure acute  1  10/13756 (0.07%)  13/13769 (0.09%) 
Cardiac failure chronic  1  47/13756 (0.34%)  50/13769 (0.36%) 
Cardiac failure congestive  1  37/13756 (0.27%)  46/13769 (0.33%) 
Cardiac flutter  1  0/13756 (0.00%)  1/13769 (0.01%) 
Cardiac tamponade  1  1/13756 (0.01%)  0/13769 (0.00%) 
Cardiac ventricular thrombosis  1  1/13756 (0.01%)  0/13769 (0.00%) 
Cardio-respiratory arrest  1  1/13756 (0.01%)  2/13769 (0.01%) 
Cardiogenic shock  1  3/13756 (0.02%)  2/13769 (0.01%) 
Cardiomyopathy  1  4/13756 (0.03%)  2/13769 (0.01%) 
Cardiopulmonary failure  1  0/13756 (0.00%)  1/13769 (0.01%) 
Cardiorenal syndrome  1  1/13756 (0.01%)  0/13769 (0.00%) 
Cardiotoxicity  1  1/13756 (0.01%)  0/13769 (0.00%) 
Cardiovascular disorder  1  0/13756 (0.00%)  1/13769 (0.01%) 
Congestive cardiomyopathy  1  2/13756 (0.01%)  1/13769 (0.01%) 
Coronary artery disease  1  46/13756 (0.33%)  32/13769 (0.23%) 
Coronary artery occlusion  1  4/13756 (0.03%)  1/13769 (0.01%) 
Coronary artery stenosis  1  4/13756 (0.03%)  5/13769 (0.04%) 
Coronary artery thrombosis  1  0/13756 (0.00%)  1/13769 (0.01%) 
Diastolic dysfunction  1  1/13756 (0.01%)  0/13769 (0.00%) 
Dressler's syndrome  1  1/13756 (0.01%)  1/13769 (0.01%) 
Extrasystoles  1  0/13756 (0.00%)  1/13769 (0.01%) 
Heart alternation  1  1/13756 (0.01%)  0/13769 (0.00%) 
Heart valve incompetence  1  1/13756 (0.01%)  0/13769 (0.00%) 
Hypertensive cardiomyopathy  1  0/13756 (0.00%)  1/13769 (0.01%) 
Hypertensive heart disease  1  1/13756 (0.01%)  1/13769 (0.01%) 
Intracardiac thrombus  1  0/13756 (0.00%)  2/13769 (0.01%) 
Ischaemic cardiomyopathy  1  6/13756 (0.04%)  7/13769 (0.05%) 
Left ventricular dysfunction  1  7/13756 (0.05%)  1/13769 (0.01%) 
Left ventricular failure  1  2/13756 (0.01%)  1/13769 (0.01%) 
Microvascular coronary artery disease  1  1/13756 (0.01%)  1/13769 (0.01%) 
Mitral valve incompetence  1  3/13756 (0.02%)  11/13769 (0.08%) 
Mitral valve stenosis  1  0/13756 (0.00%)  1/13769 (0.01%) 
Myocardial infarction  1  31/13756 (0.23%)  31/13769 (0.23%) 
Myocardial ischaemia  1  21/13756 (0.15%)  26/13769 (0.19%) 
Myocardial necrosis  1  0/13756 (0.00%)  1/13769 (0.01%) 
Myocarditis  1  2/13756 (0.01%)  1/13769 (0.01%) 
Palpitations  1  8/13756 (0.06%)  7/13769 (0.05%) 
Pericardial effusion  1  2/13756 (0.01%)  3/13769 (0.02%) 
Pericarditis  1  2/13756 (0.01%)  4/13769 (0.03%) 
Prinzmetal angina  1  3/13756 (0.02%)  0/13769 (0.00%) 
Pulseless electrical activity  1  0/13756 (0.00%)  1/13769 (0.01%) 
Rhythm idioventricular  1  0/13756 (0.00%)  1/13769 (0.01%) 
Silent myocardial infarction  1  2/13756 (0.01%)  1/13769 (0.01%) 
Sinus arrest  1  1/13756 (0.01%)  1/13769 (0.01%) 
Sinus bradycardia  1  4/13756 (0.03%)  4/13769 (0.03%) 
Sinus node dysfunction  1  18/13756 (0.13%)  17/13769 (0.12%) 
Sinus tachycardia  1  0/13756 (0.00%)  1/13769 (0.01%) 
Stress cardiomyopathy  1  0/13756 (0.00%)  1/13769 (0.01%) 
Supraventricular tachycardia  1  9/13756 (0.07%)  9/13769 (0.07%) 
Tachycardia  1  4/13756 (0.03%)  3/13769 (0.02%) 
Torsade de pointes  1  1/13756 (0.01%)  1/13769 (0.01%) 
Ventricular arrhythmia  1  6/13756 (0.04%)  4/13769 (0.03%) 
Ventricular extrasystoles  1  5/13756 (0.04%)  7/13769 (0.05%) 
Ventricular fibrillation  1  8/13756 (0.06%)  12/13769 (0.09%) 
Ventricular hypertrophy  1  0/13756 (0.00%)  1/13769 (0.01%) 
Ventricular tachyarrhythmia  1  0/13756 (0.00%)  2/13769 (0.01%) 
Ventricular tachycardia  1  27/13756 (0.20%)  23/13769 (0.17%) 
Congenital, familial and genetic disorders     
Adenomatous polyposis coli  1  1/13756 (0.01%)  2/13769 (0.01%) 
Arteriovenous malformation  1  0/13756 (0.00%)  1/13769 (0.01%) 
Atrial septal defect  1  2/13756 (0.01%)  0/13769 (0.00%) 
Carbohydrate metabolism disorder  1  2/13756 (0.01%)  0/13769 (0.00%) 
Corneal dystrophy  1  1/13756 (0.01%)  1/13769 (0.01%) 
Exomphalos  1  0/13756 (0.00%)  1/13769 (0.01%) 
Gastrointestinal arteriovenous malformation  1  1/13756 (0.01%)  0/13769 (0.00%) 
Hereditary motor and sensory neuropathy  1  0/13756 (0.00%)  1/13769 (0.01%) 
Hydrocele  1  1/13756 (0.01%)  2/13769 (0.01%) 
Hypertrophic cardiomyopathy  1  0/13756 (0.00%)  1/13769 (0.01%) 
Intracranial lipoma  1  1/13756 (0.01%)  0/13769 (0.00%) 
Subependymal nodular heterotopia  1  1/13756 (0.01%)  0/13769 (0.00%) 
Ear and labyrinth disorders     
Acute vestibular syndrome  1  0/13756 (0.00%)  2/13769 (0.01%) 
Deafness  1  1/13756 (0.01%)  1/13769 (0.01%) 
Deafness neurosensory  1  1/13756 (0.01%)  1/13769 (0.01%) 
Deafness unilateral  1  1/13756 (0.01%)  0/13769 (0.00%) 
Hypoacusis  1  1/13756 (0.01%)  0/13769 (0.00%) 
Inner ear inflammation  1  0/13756 (0.00%)  1/13769 (0.01%) 
Meniere's disease  1  1/13756 (0.01%)  2/13769 (0.01%) 
Otorrhoea  1  0/13756 (0.00%)  1/13769 (0.01%) 
Sudden hearing loss  1  1/13756 (0.01%)  1/13769 (0.01%) 
Tinnitus  1  0/13756 (0.00%)  1/13769 (0.01%) 
Vertigo  1  13/13756 (0.09%)  9/13769 (0.07%) 
Vertigo positional  1  1/13756 (0.01%)  7/13769 (0.05%) 
Vestibular disorder  1  1/13756 (0.01%)  0/13769 (0.00%) 
Vestibular ischaemia  1  0/13756 (0.00%)  1/13769 (0.01%) 
Endocrine disorders     
Adrenal insufficiency  1  1/13756 (0.01%)  1/13769 (0.01%) 
Adrenal mass  1  0/13756 (0.00%)  1/13769 (0.01%) 
Basedow's disease  1  1/13756 (0.01%)  0/13769 (0.00%) 
Goitre  1  3/13756 (0.02%)  3/13769 (0.02%) 
Hyperparathyroidism  1  1/13756 (0.01%)  0/13769 (0.00%) 
Hyperparathyroidism primary  1  1/13756 (0.01%)  1/13769 (0.01%) 
Hyperthyroidism  1  3/13756 (0.02%)  4/13769 (0.03%) 
Hypoaldosteronism  1  1/13756 (0.01%)  0/13769 (0.00%) 
Inappropriate antidiuretic hormone secretion  1  0/13756 (0.00%)  1/13769 (0.01%) 
Thyroid mass  1  4/13756 (0.03%)  1/13769 (0.01%) 
Eye disorders     
Angle closure glaucoma  1  0/13756 (0.00%)  1/13769 (0.01%) 
Blepharochalasis  1  1/13756 (0.01%)  0/13769 (0.00%) 
Cataract  1  22/13756 (0.16%)  15/13769 (0.11%) 
Cataract nuclear  1  1/13756 (0.01%)  0/13769 (0.00%) 
Dacryoadenitis acquired  1  1/13756 (0.01%)  0/13769 (0.00%) 
Diabetic retinopathy  1  0/13756 (0.00%)  2/13769 (0.01%) 
Ectropion  1  1/13756 (0.01%)  0/13769 (0.00%) 
Eyelid ptosis  1  2/13756 (0.01%)  1/13769 (0.01%) 
Glaucoma  1  1/13756 (0.01%)  1/13769 (0.01%) 
Iridocyclitis  1  1/13756 (0.01%)  1/13769 (0.01%) 
Macular degeneration  1  1/13756 (0.01%)  1/13769 (0.01%) 
Macular fibrosis  1  1/13756 (0.01%)  3/13769 (0.02%) 
Ocular myasthenia  1  0/13756 (0.00%)  1/13769 (0.01%) 
Ophthalmoplegia  1  0/13756 (0.00%)  1/13769 (0.01%) 
Pterygium  1  0/13756 (0.00%)  1/13769 (0.01%) 
Retinal artery occlusion  1  0/13756 (0.00%)  1/13769 (0.01%) 
Retinal artery thrombosis  1  1/13756 (0.01%)  0/13769 (0.00%) 
Retinal detachment  1  5/13756 (0.04%)  3/13769 (0.02%) 
Retinal tear  1  0/13756 (0.00%)  1/13769 (0.01%) 
Retinal vascular disorder  1  1/13756 (0.01%)  0/13769 (0.00%) 
Retinal vein thrombosis  1  1/13756 (0.01%)  0/13769 (0.00%) 
Strabismus  1  1/13756 (0.01%)  1/13769 (0.01%) 
Uveitis  1  1/13756 (0.01%)  0/13769 (0.00%) 
Visual acuity reduced  1  0/13756 (0.00%)  1/13769 (0.01%) 
Visual impairment  1  1/13756 (0.01%)  0/13769 (0.00%) 
Vitreous floaters  1  1/13756 (0.01%)  0/13769 (0.00%) 
Vitreous haemorrhage  1  1/13756 (0.01%)  2/13769 (0.01%) 
Gastrointestinal disorders     
Abdominal adhesions  1  1/13756 (0.01%)  1/13769 (0.01%) 
Abdominal discomfort  1  1/13756 (0.01%)  1/13769 (0.01%) 
Abdominal distension  1  1/13756 (0.01%)  2/13769 (0.01%) 
Abdominal hernia  1  8/13756 (0.06%)  11/13769 (0.08%) 
Abdominal pain  1  19/13756 (0.14%)  12/13769 (0.09%) 
Abdominal pain lower  1  2/13756 (0.01%)  2/13769 (0.01%) 
Abdominal pain upper  1  13/13756 (0.09%)  12/13769 (0.09%) 
Abdominal wall haematoma  1  0/13756 (0.00%)  2/13769 (0.01%) 
Alcoholic pancreatitis  1  2/13756 (0.01%)  0/13769 (0.00%) 
Anal fissure  1  1/13756 (0.01%)  2/13769 (0.01%) 
Anal fistula  1  4/13756 (0.03%)  1/13769 (0.01%) 
Anal incontinence  1  0/13756 (0.00%)  1/13769 (0.01%) 
Anastomotic ulcer perforation  1  1/13756 (0.01%)  0/13769 (0.00%) 
Ascites  1  3/13756 (0.02%)  1/13769 (0.01%) 
Barrett's oesophagus  1  2/13756 (0.01%)  1/13769 (0.01%) 
Chronic gastritis  1  1/13756 (0.01%)  3/13769 (0.02%) 
Coeliac artery stenosis  1  3/13756 (0.02%)  0/13769 (0.00%) 
Colitis  1  8/13756 (0.06%)  6/13769 (0.04%) 
Colitis ischaemic  1  2/13756 (0.01%)  10/13769 (0.07%) 
Colitis ulcerative  1  5/13756 (0.04%)  2/13769 (0.01%) 
Colonic fistula  1  1/13756 (0.01%)  0/13769 (0.00%) 
Constipation  1  9/13756 (0.07%)  9/13769 (0.07%) 
Crohn's disease  1  1/13756 (0.01%)  2/13769 (0.01%) 
Diarrhoea  1  4/13756 (0.03%)  9/13769 (0.07%) 
Diverticulum  1  4/13756 (0.03%)  4/13769 (0.03%) 
Diverticulum intestinal  1  3/13756 (0.02%)  3/13769 (0.02%) 
Diverticulum intestinal haemorrhagic  1  4/13756 (0.03%)  1/13769 (0.01%) 
Duodenal ulcer  1  5/13756 (0.04%)  5/13769 (0.04%) 
Duodenal ulcer haemorrhage  1  5/13756 (0.04%)  5/13769 (0.04%) 
Duodenitis  1  5/13756 (0.04%)  1/13769 (0.01%) 
Dyspepsia  1  4/13756 (0.03%)  7/13769 (0.05%) 
Dysphagia  1  4/13756 (0.03%)  1/13769 (0.01%) 
Enteritis  1  2/13756 (0.01%)  0/13769 (0.00%) 
Enterocolitis  1  1/13756 (0.01%)  0/13769 (0.00%) 
Epiploic appendagitis  1  0/13756 (0.00%)  2/13769 (0.01%) 
Erosive oesophagitis  1  1/13756 (0.01%)  1/13769 (0.01%) 
Faecaloma  1  0/13756 (0.00%)  4/13769 (0.03%) 
Food poisoning  1  1/13756 (0.01%)  4/13769 (0.03%) 
Gastric cyst  1  1/13756 (0.01%)  0/13769 (0.00%) 
Gastric disorder  1  1/13756 (0.01%)  0/13769 (0.00%) 
Gastric haemorrhage  1  2/13756 (0.01%)  0/13769 (0.00%) 
Gastric ulcer  1  8/13756 (0.06%)  9/13769 (0.07%) 
Gastric ulcer haemorrhage  1  6/13756 (0.04%)  7/13769 (0.05%) 
Gastric ulcer perforation  1  0/13756 (0.00%)  2/13769 (0.01%) 
Gastritis  1  17/13756 (0.12%)  19/13769 (0.14%) 
Gastritis alcoholic  1  0/13756 (0.00%)  1/13769 (0.01%) 
Gastritis erosive  1  3/13756 (0.02%)  3/13769 (0.02%) 
Gastritis haemorrhagic  1  3/13756 (0.02%)  0/13769 (0.00%) 
Gastroduodenal haemorrhage  1  0/13756 (0.00%)  1/13769 (0.01%) 
Gastroduodenitis  1  1/13756 (0.01%)  1/13769 (0.01%) 
Gastrointestinal angiodysplasia  1  0/13756 (0.00%)  2/13769 (0.01%) 
Gastrointestinal angiodysplasia haemorrhagic  1  1/13756 (0.01%)  0/13769 (0.00%) 
Gastrointestinal haemorrhage  1  16/13756 (0.12%)  27/13769 (0.20%) 
Gastrointestinal pain  1  0/13756 (0.00%)  1/13769 (0.01%) 
Gastrointestinal polyp haemorrhage  1  2/13756 (0.01%)  0/13769 (0.00%) 
Gastrointestinal ulcer  1  1/13756 (0.01%)  0/13769 (0.00%) 
Gastrointestinal ulcer haemorrhage  1  0/13756 (0.00%)  1/13769 (0.01%) 
Gastrooesophageal reflux disease  1  15/13756 (0.11%)  14/13769 (0.10%) 
Haematemesis  1  2/13756 (0.01%)  4/13769 (0.03%) 
Haematochezia  1  1/13756 (0.01%)  4/13769 (0.03%) 
Haemorrhagic erosive gastritis  1  0/13756 (0.00%)  2/13769 (0.01%) 
Haemorrhoidal haemorrhage  1  5/13756 (0.04%)  3/13769 (0.02%) 
Haemorrhoids  1  10/13756 (0.07%)  6/13769 (0.04%) 
Haemorrhoids thrombosed  1  0/13756 (0.00%)  1/13769 (0.01%) 
Hernial eventration  1  0/13756 (0.00%)  2/13769 (0.01%) 
Hiatus hernia  1  3/13756 (0.02%)  9/13769 (0.07%) 
Ileus  1  7/13756 (0.05%)  6/13769 (0.04%) 
Ileus paralytic  1  2/13756 (0.01%)  0/13769 (0.00%) 
Impaired gastric emptying  1  1/13756 (0.01%)  3/13769 (0.02%) 
Incarcerated inguinal hernia  1  1/13756 (0.01%)  1/13769 (0.01%) 
Incarcerated umbilical hernia  1  0/13756 (0.00%)  1/13769 (0.01%) 
Inflammatory bowel disease  1  1/13756 (0.01%)  0/13769 (0.00%) 
Inguinal hernia  1  22/13756 (0.16%)  32/13769 (0.23%) 
Intestinal dilatation  1  1/13756 (0.01%)  0/13769 (0.00%) 
Intestinal fistula  1  0/13756 (0.00%)  1/13769 (0.01%) 
Intestinal haemorrhage  1  0/13756 (0.00%)  1/13769 (0.01%) 
Intestinal ischaemia  1  2/13756 (0.01%)  0/13769 (0.00%) 
Intestinal obstruction  1  5/13756 (0.04%)  3/13769 (0.02%) 
Intestinal polyp  1  2/13756 (0.01%)  1/13769 (0.01%) 
Intestinal prolapse  1  0/13756 (0.00%)  1/13769 (0.01%) 
Intra-abdominal fluid collection  1  1/13756 (0.01%)  0/13769 (0.00%) 
Intra-abdominal haematoma  1  1/13756 (0.01%)  0/13769 (0.00%) 
Intra-abdominal haemorrhage  1  1/13756 (0.01%)  0/13769 (0.00%) 
Intussusception  1  0/13756 (0.00%)  1/13769 (0.01%) 
Irritable bowel syndrome  1  1/13756 (0.01%)  0/13769 (0.00%) 
Large intestinal haemorrhage  1  1/13756 (0.01%)  1/13769 (0.01%) 
Large intestinal obstruction  1  3/13756 (0.02%)  1/13769 (0.01%) 
Large intestinal ulcer  1  1/13756 (0.01%)  0/13769 (0.00%) 
Large intestine perforation  1  0/13756 (0.00%)  1/13769 (0.01%) 
Large intestine polyp  1  16/13756 (0.12%)  10/13769 (0.07%) 
Leukoplakia oral  1  1/13756 (0.01%)  0/13769 (0.00%) 
Lower gastrointestinal haemorrhage  1  3/13756 (0.02%)  2/13769 (0.01%) 
Mallory-Weiss syndrome  1  2/13756 (0.01%)  0/13769 (0.00%) 
Mechanical ileus  1  1/13756 (0.01%)  0/13769 (0.00%) 
Melaena  1  2/13756 (0.01%)  1/13769 (0.01%) 
Mesenteric arterial occlusion  1  1/13756 (0.01%)  0/13769 (0.00%) 
Mesenteric artery stenosis  1  1/13756 (0.01%)  1/13769 (0.01%) 
Mesenteric artery thrombosis  1  1/13756 (0.01%)  0/13769 (0.00%) 
Mesenteric vein thrombosis  1  1/13756 (0.01%)  0/13769 (0.00%) 
Nausea  1  4/13756 (0.03%)  5/13769 (0.04%) 
Odynophagia  1  1/13756 (0.01%)  0/13769 (0.00%) 
Oesophageal achalasia  1  1/13756 (0.01%)  1/13769 (0.01%) 
Oesophageal food impaction  1  1/13756 (0.01%)  0/13769 (0.00%) 
Oesophageal obstruction  1  0/13756 (0.00%)  1/13769 (0.01%) 
Oesophageal spasm  1  3/13756 (0.02%)  2/13769 (0.01%) 
Oesophageal stenosis  1  2/13756 (0.01%)  0/13769 (0.00%) 
Oesophageal ulcer  1  1/13756 (0.01%)  2/13769 (0.01%) 
Oesophageal varices haemorrhage  1  1/13756 (0.01%)  0/13769 (0.00%) 
Oesophagitis  1  4/13756 (0.03%)  1/13769 (0.01%) 
Oesophagitis ulcerative  1  1/13756 (0.01%)  0/13769 (0.00%) 
Palatal swelling  1  1/13756 (0.01%)  0/13769 (0.00%) 
Pancreatic cyst  1  2/13756 (0.01%)  0/13769 (0.00%) 
Pancreatic disorder  1  1/13756 (0.01%)  0/13769 (0.00%) 
Pancreatic necrosis  1  1/13756 (0.01%)  0/13769 (0.00%) 
Pancreatic phlegmon  1  1/13756 (0.01%)  0/13769 (0.00%) 
Pancreatic pseudocyst  1  0/13756 (0.00%)  1/13769 (0.01%) 
Pancreatitis  1  16/13756 (0.12%)  10/13769 (0.07%) 
Pancreatitis acute  1  22/13756 (0.16%)  14/13769 (0.10%) 
Pancreatitis chronic  1  0/13756 (0.00%)  1/13769 (0.01%) 
Pancreatitis necrotising  1  1/13756 (0.01%)  3/13769 (0.02%) 
Pancreatolithiasis  1  1/13756 (0.01%)  1/13769 (0.01%) 
Peptic ulcer  1  2/13756 (0.01%)  1/13769 (0.01%) 
Peptic ulcer haemorrhage  1  2/13756 (0.01%)  1/13769 (0.01%) 
Periodontal disease  1  0/13756 (0.00%)  1/13769 (0.01%) 
Peritoneal haematoma  1  0/13756 (0.00%)  1/13769 (0.01%) 
Proctitis  1  2/13756 (0.01%)  0/13769 (0.00%) 
Rectal haemorrhage  1  9/13756 (0.07%)  6/13769 (0.04%) 
Rectal polyp  1  2/13756 (0.01%)  0/13769 (0.00%) 
Reflux gastritis  1  0/13756 (0.00%)  1/13769 (0.01%) 
Retching  1  1/13756 (0.01%)  0/13769 (0.00%) 
Retroperitoneal fibrosis  1  1/13756 (0.01%)  0/13769 (0.00%) 
Retroperitoneal haematoma  1  1/13756 (0.01%)  1/13769 (0.01%) 
Retroperitoneal haemorrhage  1  1/13756 (0.01%)  0/13769 (0.00%) 
Salivary gland enlargement  1  0/13756 (0.00%)  2/13769 (0.01%) 
Small intestinal haemorrhage  1  0/13756 (0.00%)  1/13769 (0.01%) 
Small intestinal obstruction  1  6/13756 (0.04%)  4/13769 (0.03%) 
Small intestine ulcer  1  1/13756 (0.01%)  0/13769 (0.00%) 
Strangulated umbilical hernia  1  1/13756 (0.01%)  1/13769 (0.01%) 
Stress ulcer  1  1/13756 (0.01%)  0/13769 (0.00%) 
Thrombosis mesenteric vessel  1  0/13756 (0.00%)  1/13769 (0.01%) 
Tongue cyst  1  0/13756 (0.00%)  1/13769 (0.01%) 
Tongue oedema  1  1/13756 (0.01%)  1/13769 (0.01%) 
Tooth disorder  1  1/13756 (0.01%)  0/13769 (0.00%) 
Tooth impacted  1  0/13756 (0.00%)  1/13769 (0.01%) 
Umbilical hernia  1  14/13756 (0.10%)  10/13769 (0.07%) 
Upper gastrointestinal haemorrhage  1  9/13756 (0.07%)  13/13769 (0.09%) 
Varices oesophageal  1  1/13756 (0.01%)  1/13769 (0.01%) 
Volvulus  1  1/13756 (0.01%)  0/13769 (0.00%) 
Vomiting  1  10/13756 (0.07%)  4/13769 (0.03%) 
General disorders     
Asthenia  1  6/13756 (0.04%)  8/13769 (0.06%) 
Breakthrough pain  1  1/13756 (0.01%)  0/13769 (0.00%) 
Catheter site extravasation  1  1/13756 (0.01%)  0/13769 (0.00%) 
Chest discomfort  1  5/13756 (0.04%)  4/13769 (0.03%) 
Chest pain  1  49/13756 (0.36%)  42/13769 (0.31%) 
Complication associated with device  1  0/13756 (0.00%)  2/13769 (0.01%) 
Cyst rupture  1  0/13756 (0.00%)  1/13769 (0.01%) 
Drug intolerance  1  0/13756 (0.00%)  1/13769 (0.01%) 
Drug withdrawal syndrome  1  0/13756 (0.00%)  1/13769 (0.01%) 
Exercise tolerance decreased  1  0/13756 (0.00%)  2/13769 (0.01%) 
Fat necrosis  1  0/13756 (0.00%)  1/13769 (0.01%) 
Fatigue  1  4/13756 (0.03%)  2/13769 (0.01%) 
Gait disturbance  1  0/13756 (0.00%)  5/13769 (0.04%) 
General physical health deterioration  1  0/13756 (0.00%)  1/13769 (0.01%) 
Generalised oedema  1  1/13756 (0.01%)  0/13769 (0.00%) 
Hernia  1  1/13756 (0.01%)  2/13769 (0.01%) 
Impaired healing  1  5/13756 (0.04%)  4/13769 (0.03%) 
Implant site inflammation  1  0/13756 (0.00%)  1/13769 (0.01%) 
Incarcerated hernia  1  0/13756 (0.00%)  2/13769 (0.01%) 
Inflammation  1  2/13756 (0.01%)  0/13769 (0.00%) 
Malaise  1  1/13756 (0.01%)  3/13769 (0.02%) 
Mass  1  0/13756 (0.00%)  1/13769 (0.01%) 
Medical device discomfort  1  1/13756 (0.01%)  1/13769 (0.01%) 
Mucosal inflammation  1  1/13756 (0.01%)  0/13769 (0.00%) 
Multiple organ dysfunction syndrome  1  0/13756 (0.00%)  4/13769 (0.03%) 
Non-cardiac chest pain  1  133/13756 (0.97%)  109/13769 (0.79%) 
Oedema peripheral  1  1/13756 (0.01%)  4/13769 (0.03%) 
Pacemaker generated arrhythmia  1  1/13756 (0.01%)  0/13769 (0.00%) 
Pain  1  0/13756 (0.00%)  1/13769 (0.01%) 
Peripheral swelling  1  1/13756 (0.01%)  0/13769 (0.00%) 
Pyrexia  1  9/13756 (0.07%)  5/13769 (0.04%) 
Sensation of foreign body  1  1/13756 (0.01%)  0/13769 (0.00%) 
Soft tissue inflammation  1  0/13756 (0.00%)  1/13769 (0.01%) 
Strangulated hernia  1  0/13756 (0.00%)  1/13769 (0.01%) 
Sudden cardiac death  1  1/13756 (0.01%)  0/13769 (0.00%) 
Surgical failure  1  2/13756 (0.01%)  0/13769 (0.00%) 
Systemic inflammatory response syndrome  1  3/13756 (0.02%)  1/13769 (0.01%) 
Vascular stent occlusion  1  1/13756 (0.01%)  1/13769 (0.01%) 
Vascular stent restenosis  1  1/13756 (0.01%)  2/13769 (0.01%) 
Vascular stent stenosis  1  3/13756 (0.02%)  2/13769 (0.01%) 
Vascular stent thrombosis  1  1/13756 (0.01%)  0/13769 (0.00%) 
Hepatobiliary disorders     
Acute hepatic failure  1  1/13756 (0.01%)  1/13769 (0.01%) 
Ampulla of Vater stenosis  1  1/13756 (0.01%)  0/13769 (0.00%) 
Autoimmune hepatitis  1  0/13756 (0.00%)  2/13769 (0.01%) 
Bile duct obstruction  1  1/13756 (0.01%)  1/13769 (0.01%) 
Bile duct stenosis  1  1/13756 (0.01%)  1/13769 (0.01%) 
Bile duct stone  1  5/13756 (0.04%)  6/13769 (0.04%) 
Biliary colic  1  5/13756 (0.04%)  4/13769 (0.03%) 
Biliary cyst  1  1/13756 (0.01%)  0/13769 (0.00%) 
Cholangitis  1  2/13756 (0.01%)  5/13769 (0.04%) 
Cholangitis acute  1  6/13756 (0.04%)  0/13769 (0.00%) 
Cholecystitis  1  7/13756 (0.05%)  14/13769 (0.10%) 
Cholecystitis acute  1  31/13756 (0.23%)  40/13769 (0.29%) 
Cholecystitis chronic  1  5/13756 (0.04%)  5/13769 (0.04%) 
Cholecystocholangitis  1  1/13756 (0.01%)  0/13769 (0.00%) 
Cholelithiasis  1  23/13756 (0.17%)  27/13769 (0.20%) 
Cholelithiasis migration  1  1/13756 (0.01%)  0/13769 (0.00%) 
Cholelithiasis obstructive  1  0/13756 (0.00%)  1/13769 (0.01%) 
Cholestasis  1  1/13756 (0.01%)  0/13769 (0.00%) 
Cirrhosis alcoholic  1  0/13756 (0.00%)  1/13769 (0.01%) 
Drug-induced liver injury  1  0/13756 (0.00%)  3/13769 (0.02%) 
Gallbladder perforation  1  0/13756 (0.00%)  1/13769 (0.01%) 
Gallbladder polyp  1  0/13756 (0.00%)  1/13769 (0.01%) 
Hepatic cirrhosis  1  2/13756 (0.01%)  1/13769 (0.01%) 
Hepatic cyst  1  0/13756 (0.00%)  1/13769 (0.01%) 
Hepatic failure  1  0/13756 (0.00%)  2/13769 (0.01%) 
Hepatic fibrosis  1  1/13756 (0.01%)  0/13769 (0.00%) 
Hepatic function abnormal  1  0/13756 (0.00%)  1/13769 (0.01%) 
Hepatic pain  1  0/13756 (0.00%)  1/13769 (0.01%) 
Hepatic steatosis  1  2/13756 (0.01%)  0/13769 (0.00%) 
Hepatitis acute  1  1/13756 (0.01%)  0/13769 (0.00%) 
Hepatitis alcoholic  1  1/13756 (0.01%)  1/13769 (0.01%) 
Hepatitis toxic  1  0/13756 (0.00%)  1/13769 (0.01%) 
Hepatorenal syndrome  1  0/13756 (0.00%)  1/13769 (0.01%) 
Hepatotoxicity  1  1/13756 (0.01%)  1/13769 (0.01%) 
Hypertransaminasaemia  1  0/13756 (0.00%)  1/13769 (0.01%) 
Jaundice  1  0/13756 (0.00%)  1/13769 (0.01%) 
Liver disorder  1  1/13756 (0.01%)  0/13769 (0.00%) 
Porcelain gallbladder  1  1/13756 (0.01%)  0/13769 (0.00%) 
Portal vein thrombosis  1  1/13756 (0.01%)  1/13769 (0.01%) 
Subacute hepatic failure  1  0/13756 (0.00%)  1/13769 (0.01%) 
Immune system disorders     
Allergy to arthropod sting  1  0/13756 (0.00%)  2/13769 (0.01%) 
Anaphylactic reaction  1  3/13756 (0.02%)  2/13769 (0.01%) 
Anaphylactic shock  1  0/13756 (0.00%)  2/13769 (0.01%) 
Drug hypersensitivity  1  0/13756 (0.00%)  1/13769 (0.01%) 
Food allergy  1  1/13756 (0.01%)  0/13769 (0.00%) 
Hypersensitivity  1  3/13756 (0.02%)  1/13769 (0.01%) 
Mite allergy  1  0/13756 (0.00%)  1/13769 (0.01%) 
Sarcoidosis  1  1/13756 (0.01%)  0/13769 (0.00%) 
Transplant rejection  1  0/13756 (0.00%)  1/13769 (0.01%) 
Infections and infestations     
Abdominal abscess  1  1/13756 (0.01%)  0/13769 (0.00%) 
Abdominal sepsis  1  0/13756 (0.00%)  2/13769 (0.01%) 
Abdominal wall abscess  1  0/13756 (0.00%)  1/13769 (0.01%) 
Abscess  1  1/13756 (0.01%)  0/13769 (0.00%) 
Abscess bacterial  1  1/13756 (0.01%)  1/13769 (0.01%) 
Abscess limb  1  4/13756 (0.03%)  10/13769 (0.07%) 
Abscess of eyelid  1  0/13756 (0.00%)  1/13769 (0.01%) 
Abscess of salivary gland  1  0/13756 (0.00%)  1/13769 (0.01%) 
Abscess soft tissue  1  0/13756 (0.00%)  1/13769 (0.01%) 
Acute sinusitis  1  1/13756 (0.01%)  0/13769 (0.00%) 
Amoebic dysentery  1  0/13756 (0.00%)  1/13769 (0.01%) 
Anal abscess  1  5/13756 (0.04%)  2/13769 (0.01%) 
Anal fistula infection  1  1/13756 (0.01%)  0/13769 (0.00%) 
Appendiceal abscess  1  2/13756 (0.01%)  0/13769 (0.00%) 
Appendicitis  1  14/13756 (0.10%)  20/13769 (0.15%) 
Appendicitis perforated  1  5/13756 (0.04%)  2/13769 (0.01%) 
Arteritis infective  1  1/13756 (0.01%)  0/13769 (0.00%) 
Arthritis bacterial  1  2/13756 (0.01%)  0/13769 (0.00%) 
Atypical pneumonia  1  2/13756 (0.01%)  0/13769 (0.00%) 
Bacteraemia  1  1/13756 (0.01%)  1/13769 (0.01%) 
Bacterial pericarditis  1  0/13756 (0.00%)  1/13769 (0.01%) 
Bacterial prostatitis  1  1/13756 (0.01%)  0/13769 (0.00%) 
Bacterial pyelonephritis  1  0/13756 (0.00%)  1/13769 (0.01%) 
Bacterial sepsis  1  0/13756 (0.00%)  1/13769 (0.01%) 
Bacteroides bacteraemia  1  1/13756 (0.01%)  0/13769 (0.00%) 
Beta haemolytic streptococcal infection  1  1/13756 (0.01%)  0/13769 (0.00%) 
Bone abscess  1  0/13756 (0.00%)  1/13769 (0.01%) 
Breast abscess  1  0/13756 (0.00%)  2/13769 (0.01%) 
Bronchitis  1  30/13756 (0.22%)  17/13769 (0.12%) 
Bronchitis bacterial  1  2/13756 (0.01%)  2/13769 (0.01%) 
Burkholderia cepacia complex infection  1  1/13756 (0.01%)  0/13769 (0.00%) 
Burkholderia pseudomallei infection  1  0/13756 (0.00%)  1/13769 (0.01%) 
Bursitis infective  1  0/13756 (0.00%)  2/13769 (0.01%) 
Campylobacter gastroenteritis  1  1/13756 (0.01%)  2/13769 (0.01%) 
Carbuncle  1  2/13756 (0.01%)  0/13769 (0.00%) 
Catheter site infection  1  0/13756 (0.00%)  1/13769 (0.01%) 
Cellulitis  1  28/13756 (0.20%)  39/13769 (0.28%) 
Cellulitis gangrenous  1  1/13756 (0.01%)  0/13769 (0.00%) 
Cervicitis  1  0/13756 (0.00%)  1/13769 (0.01%) 
Cholecystitis infective  1  2/13756 (0.01%)  2/13769 (0.01%) 
Chronic hepatitis B  1  1/13756 (0.01%)  0/13769 (0.00%) 
Chronic sinusitis  1  0/13756 (0.00%)  1/13769 (0.01%) 
Clostridium difficile colitis  1  2/13756 (0.01%)  6/13769 (0.04%) 
Clostridium difficile infection  1  2/13756 (0.01%)  3/13769 (0.02%) 
Colonic abscess  1  0/13756 (0.00%)  1/13769 (0.01%) 
Creutzfeldt-Jakob disease  1  1/13756 (0.01%)  0/13769 (0.00%) 
Cystitis  1  5/13756 (0.04%)  3/13769 (0.02%) 
Cystitis escherichia  1  1/13756 (0.01%)  1/13769 (0.01%) 
Dengue fever  1  4/13756 (0.03%)  1/13769 (0.01%) 
Device related infection  1  3/13756 (0.02%)  1/13769 (0.01%) 
Device related sepsis  1  1/13756 (0.01%)  2/13769 (0.01%) 
Diabetic foot infection  1  6/13756 (0.04%)  2/13769 (0.01%) 
Diabetic gangrene  1  1/13756 (0.01%)  1/13769 (0.01%) 
Diarrhoea infectious  1  0/13756 (0.00%)  1/13769 (0.01%) 
Diverticulitis  1  26/13756 (0.19%)  16/13769 (0.12%) 
Diverticulitis intestinal haemorrhagic  1  0/13756 (0.00%)  1/13769 (0.01%) 
Eczema infected  1  1/13756 (0.01%)  0/13769 (0.00%) 
Embolic pneumonia  1  0/13756 (0.00%)  1/13769 (0.01%) 
Empyema  1  3/13756 (0.02%)  0/13769 (0.00%) 
Encephalitis viral  1  1/13756 (0.01%)  0/13769 (0.00%) 
Endocarditis  1  1/13756 (0.01%)  1/13769 (0.01%) 
Endocarditis bacterial  1  1/13756 (0.01%)  0/13769 (0.00%) 
Endocarditis haemophilus  1  1/13756 (0.01%)  0/13769 (0.00%) 
Endophthalmitis  1  0/13756 (0.00%)  1/13769 (0.01%) 
Enteritis infectious  1  1/13756 (0.01%)  0/13769 (0.00%) 
Enterobacter bacteraemia  1  0/13756 (0.00%)  1/13769 (0.01%) 
Enterococcal bacteraemia  1  2/13756 (0.01%)  1/13769 (0.01%) 
Enterococcal sepsis  1  0/13756 (0.00%)  1/13769 (0.01%) 
Epididymitis  1  3/13756 (0.02%)  1/13769 (0.01%) 
Epiglottitis  1  2/13756 (0.01%)  0/13769 (0.00%) 
Erysipelas  1  19/13756 (0.14%)  16/13769 (0.12%) 
Erysipeloid  1  0/13756 (0.00%)  1/13769 (0.01%) 
Escherichia bacteraemia  1  2/13756 (0.01%)  0/13769 (0.00%) 
Escherichia sepsis  1  3/13756 (0.02%)  4/13769 (0.03%) 
Escherichia urinary tract infection  1  0/13756 (0.00%)  2/13769 (0.01%) 
Febrile infection  1  0/13756 (0.00%)  1/13769 (0.01%) 
Fungal peritonitis  1  0/13756 (0.00%)  1/13769 (0.01%) 
Furuncle  1  1/13756 (0.01%)  0/13769 (0.00%) 
Gallbladder empyema  1  1/13756 (0.01%)  0/13769 (0.00%) 
Gangrene  1  12/13756 (0.09%)  6/13769 (0.04%) 
Gastritis viral  1  0/13756 (0.00%)  1/13769 (0.01%) 
Gastroenteritis  1  14/13756 (0.10%)  19/13769 (0.14%) 
Gastroenteritis adenovirus  1  0/13756 (0.00%)  1/13769 (0.01%) 
Gastroenteritis bacterial  1  0/13756 (0.00%)  2/13769 (0.01%) 
Gastroenteritis clostridial  1  0/13756 (0.00%)  1/13769 (0.01%) 
Gastroenteritis rotavirus  1  1/13756 (0.01%)  1/13769 (0.01%) 
Gastroenteritis salmonella  1  2/13756 (0.01%)  2/13769 (0.01%) 
Gastroenteritis viral  1  3/13756 (0.02%)  3/13769 (0.02%) 
Gastrointestinal infection  1  2/13756 (0.01%)  1/13769 (0.01%) 
Gingival abscess  1  1/13756 (0.01%)  0/13769 (0.00%) 
Graft infection  1  2/13756 (0.01%)  1/13769 (0.01%) 
Groin abscess  1  0/13756 (0.00%)  1/13769 (0.01%) 
H1N1 influenza  1  1/13756 (0.01%)  0/13769 (0.00%) 
Haematoma infection  1  1/13756 (0.01%)  0/13769 (0.00%) 
Helicobacter infection  1  1/13756 (0.01%)  0/13769 (0.00%) 
Hepatitis A  1  1/13756 (0.01%)  0/13769 (0.00%) 
Hepatitis B  1  2/13756 (0.01%)  1/13769 (0.01%) 
Hepatitis C  1  0/13756 (0.00%)  3/13769 (0.02%) 
Hepatitis E  1  1/13756 (0.01%)  3/13769 (0.02%) 
Herpes zoster  1  3/13756 (0.02%)  5/13769 (0.04%) 
Implant site infection  1  0/13756 (0.00%)  1/13769 (0.01%) 
Incision site infection  1  0/13756 (0.00%)  1/13769 (0.01%) 
Infected bite  1  1/13756 (0.01%)  1/13769 (0.01%) 
Infected cyst  1  3/13756 (0.02%)  0/13769 (0.00%) 
Infected skin ulcer  1  2/13756 (0.01%)  2/13769 (0.01%) 
Infection  1  0/13756 (0.00%)  1/13769 (0.01%) 
Infection in an immunocompromised host  1  1/13756 (0.01%)  0/13769 (0.00%) 
Infectious colitis  1  1/13756 (0.01%)  0/13769 (0.00%) 
Infectious pleural effusion  1  2/13756 (0.01%)  1/13769 (0.01%) 
Infective exacerbation of chronic obstructive airways disease  1  5/13756 (0.04%)  3/13769 (0.02%) 
Infective tenosynovitis  1  0/13756 (0.00%)  1/13769 (0.01%) 
Influenza  1  6/13756 (0.04%)  9/13769 (0.07%) 
Intervertebral discitis  1  0/13756 (0.00%)  1/13769 (0.01%) 
Kidney infection  1  1/13756 (0.01%)  1/13769 (0.01%) 
Laryngitis  1  2/13756 (0.01%)  1/13769 (0.01%) 
Liver abscess  1  0/13756 (0.00%)  2/13769 (0.01%) 
Localised infection  1  6/13756 (0.04%)  6/13769 (0.04%) 
Lower respiratory tract infection  1  15/13756 (0.11%)  14/13769 (0.10%) 
Lower respiratory tract infection viral  1  0/13756 (0.00%)  2/13769 (0.01%) 
Lung abscess  1  1/13756 (0.01%)  0/13769 (0.00%) 
Lung infection  1  3/13756 (0.02%)  5/13769 (0.04%) 
Mastoiditis  1  1/13756 (0.01%)  1/13769 (0.01%) 
Mediastinitis  1  0/13756 (0.00%)  1/13769 (0.01%) 
Medical device site infection  1  1/13756 (0.01%)  0/13769 (0.00%) 
Meningitis  1  1/13756 (0.01%)  0/13769 (0.00%) 
Meningitis bacterial  1  0/13756 (0.00%)  1/13769 (0.01%) 
Meningitis pneumococcal  1  1/13756 (0.01%)  0/13769 (0.00%) 
Muscle abscess  1  0/13756 (0.00%)  1/13769 (0.01%) 
Nasopharyngitis  1  0/13756 (0.00%)  1/13769 (0.01%) 
Necrotising fasciitis  1  1/13756 (0.01%)  2/13769 (0.01%) 
Neurosyphilis  1  0/13756 (0.00%)  1/13769 (0.01%) 
Neutropenic infection  1  1/13756 (0.01%)  0/13769 (0.00%) 
Nosocomial infection  1  1/13756 (0.01%)  0/13769 (0.00%) 
Ophthalmic herpes zoster  1  1/13756 (0.01%)  1/13769 (0.01%) 
Oral fungal infection  1  1/13756 (0.01%)  0/13769 (0.00%) 
Orchitis  1  2/13756 (0.01%)  2/13769 (0.01%) 
Osteomyelitis  1  7/13756 (0.05%)  16/13769 (0.12%) 
Osteomyelitis acute  1  1/13756 (0.01%)  1/13769 (0.01%) 
Osteomyelitis chronic  1  2/13756 (0.01%)  0/13769 (0.00%) 
Otitis externa  1  0/13756 (0.00%)  1/13769 (0.01%) 
Otitis externa bacterial  1  0/13756 (0.00%)  1/13769 (0.01%) 
Otitis media  1  0/13756 (0.00%)  2/13769 (0.01%) 
Pancreas infection  1  0/13756 (0.00%)  1/13769 (0.01%) 
Paronychia  1  0/13756 (0.00%)  1/13769 (0.01%) 
Parotitis  1  1/13756 (0.01%)  0/13769 (0.00%) 
Pelvic abscess  1  2/13756 (0.01%)  0/13769 (0.00%) 
Perineal abscess  1  1/13756 (0.01%)  0/13769 (0.00%) 
Periodontitis  1  2/13756 (0.01%)  1/13769 (0.01%) 
Perirectal abscess  1  0/13756 (0.00%)  1/13769 (0.01%) 
Peritonitis  1  2/13756 (0.01%)  4/13769 (0.03%) 
Peritonitis bacterial  1  2/13756 (0.01%)  1/13769 (0.01%) 
Pharyngeal abscess  1  1/13756 (0.01%)  0/13769 (0.00%) 
Pharyngitis  1  0/13756 (0.00%)  1/13769 (0.01%) 
Pharyngitis streptococcal  1  1/13756 (0.01%)  0/13769 (0.00%) 
Pneumococcal sepsis  1  0/13756 (0.00%)  1/13769 (0.01%) 
Pneumonia  1  152/13756 (1.10%)  147/13769 (1.07%) 
Pneumonia adenoviral  1  0/13756 (0.00%)  1/13769 (0.01%) 
Pneumonia bacterial  1  11/13756 (0.08%)  18/13769 (0.13%) 
Pneumonia influenzal  1  1/13756 (0.01%)  1/13769 (0.01%) 
Pneumonia legionella  1  1/13756 (0.01%)  1/13769 (0.01%) 
Pneumonia pneumococcal  1  1/13756 (0.01%)  0/13769 (0.00%) 
Pneumonia staphylococcal  1  2/13756 (0.01%)  0/13769 (0.00%) 
Pneumonia viral  1  0/13756 (0.00%)  1/13769 (0.01%) 
Post procedural infection  1  3/13756 (0.02%)  4/13769 (0.03%) 
Post procedural pneumonia  1  1/13756 (0.01%)  0/13769 (0.00%) 
Post procedural sepsis  1  1/13756 (0.01%)  1/13769 (0.01%) 
Postoperative abscess  1  4/13756 (0.03%)  0/13769 (0.00%) 
Postoperative wound infection  1  8/13756 (0.06%)  3/13769 (0.02%) 
Prostate infection  1  0/13756 (0.00%)  1/13769 (0.01%) 
Prostatic abscess  1  1/13756 (0.01%)  1/13769 (0.01%) 
Pseudomembranous colitis  1  1/13756 (0.01%)  1/13769 (0.01%) 
Psoas abscess  1  0/13756 (0.00%)  1/13769 (0.01%) 
Pulmonary sepsis  1  1/13756 (0.01%)  0/13769 (0.00%) 
Pulmonary tuberculosis  1  3/13756 (0.02%)  0/13769 (0.00%) 
Pyelonephritis  1  4/13756 (0.03%)  10/13769 (0.07%) 
Pyelonephritis acute  1  6/13756 (0.04%)  6/13769 (0.04%) 
Pyelonephritis chronic  1  0/13756 (0.00%)  1/13769 (0.01%) 
Pyonephrosis  1  1/13756 (0.01%)  1/13769 (0.01%) 
Rectal abscess  1  1/13756 (0.01%)  1/13769 (0.01%) 
Respiratory tract infection  1  8/13756 (0.06%)  8/13769 (0.06%) 
Respiratory tract infection bacterial  1  0/13756 (0.00%)  1/13769 (0.01%) 
Rhinitis  1  0/13756 (0.00%)  1/13769 (0.01%) 
Rhinovirus infection  1  0/13756 (0.00%)  1/13769 (0.01%) 
Salmonellosis  1  0/13756 (0.00%)  1/13769 (0.01%) 
Salpingitis  1  0/13756 (0.00%)  1/13769 (0.01%) 
Scrotal abscess  1  1/13756 (0.01%)  1/13769 (0.01%) 
Scrotal infection  1  1/13756 (0.01%)  0/13769 (0.00%) 
Sepsis  1  31/13756 (0.23%)  21/13769 (0.15%) 
Septic shock  1  9/13756 (0.07%)  6/13769 (0.04%) 
Sinusitis  1  1/13756 (0.01%)  1/13769 (0.01%) 
Skin bacterial infection  1  0/13756 (0.00%)  1/13769 (0.01%) 
Skin infection  1  2/13756 (0.01%)  1/13769 (0.01%) 
Soft tissue infection  1  1/13756 (0.01%)  0/13769 (0.00%) 
Spermatic cord funiculitis  1  0/13756 (0.00%)  1/13769 (0.01%) 
Splenic abscess  1  1/13756 (0.01%)  0/13769 (0.00%) 
Staphylococcal abscess  1  1/13756 (0.01%)  0/13769 (0.00%) 
Staphylococcal bacteraemia  1  3/13756 (0.02%)  1/13769 (0.01%) 
Staphylococcal infection  1  2/13756 (0.01%)  0/13769 (0.00%) 
Staphylococcal sepsis  1  2/13756 (0.01%)  1/13769 (0.01%) 
Streptococcal sepsis  1  1/13756 (0.01%)  2/13769 (0.01%) 
Subcutaneous abscess  1  1/13756 (0.01%)  2/13769 (0.01%) 
Testicular abscess  1  0/13756 (0.00%)  1/13769 (0.01%) 
Tick-borne viral encephalitis  1  1/13756 (0.01%)  0/13769 (0.00%) 
Tonsillitis  1  1/13756 (0.01%)  0/13769 (0.00%) 
Tooth abscess  1  1/13756 (0.01%)  3/13769 (0.02%) 
Tracheitis  1  0/13756 (0.00%)  2/13769 (0.01%) 
Tracheobronchitis  1  3/13756 (0.02%)  0/13769 (0.00%) 
Tuberculosis  1  0/13756 (0.00%)  1/13769 (0.01%) 
Upper respiratory tract infection  1  6/13756 (0.04%)  6/13769 (0.04%) 
Upper respiratory tract infection bacterial  1  3/13756 (0.02%)  0/13769 (0.00%) 
Ureteritis  1  0/13756 (0.00%)  1/13769 (0.01%) 
Urinary tract infection  1  37/13756 (0.27%)  41/13769 (0.30%) 
Urinary tract infection bacterial  1  7/13756 (0.05%)  7/13769 (0.05%) 
Urosepsis  1  15/13756 (0.11%)  12/13769 (0.09%) 
Vestibular neuronitis  1  1/13756 (0.01%)  2/13769 (0.01%) 
Viral infection  1  3/13756 (0.02%)  4/13769 (0.03%) 
Viral myocarditis  1  1/13756 (0.01%)  0/13769 (0.00%) 
Viral pericarditis  1  0/13756 (0.00%)  2/13769 (0.01%) 
Viral upper respiratory tract infection  1  1/13756 (0.01%)  0/13769 (0.00%) 
Vulval abscess  1  1/13756 (0.01%)  2/13769 (0.01%) 
Wound abscess  1  0/13756 (0.00%)  1/13769 (0.01%) 
Wound infection  1  11/13756 (0.08%)  6/13769 (0.04%) 
Wound infection bacterial  1  1/13756 (0.01%)  0/13769 (0.00%) 
Wound infection staphylococcal  1  0/13756 (0.00%)  1/13769 (0.01%) 
Wound sepsis  1  2/13756 (0.01%)  0/13769 (0.00%) 
Injury, poisoning and procedural complications     
Abdominal injury  1  0/13756 (0.00%)  1/13769 (0.01%) 
Accidental overdose  1  2/13756 (0.01%)  3/13769 (0.02%) 
Acetabulum fracture  1  2/13756 (0.01%)  0/13769 (0.00%) 
Alcohol poisoning  1  3/13756 (0.02%)  3/13769 (0.02%) 
Anaemia postoperative  1  0/13756 (0.00%)  1/13769 (0.01%) 
Anastomotic fistula  1  0/13756 (0.00%)  1/13769 (0.01%) 
Anastomotic leak  1  1/13756 (0.01%)  0/13769 (0.00%) 
Anastomotic stenosis  1  1/13756 (0.01%)  0/13769 (0.00%) 
Animal bite  1  0/13756 (0.00%)  2/13769 (0.01%) 
Animal scratch  1  0/13756 (0.00%)  1/13769 (0.01%) 
Ankle fracture  1  12/13756 (0.09%)  8/13769 (0.06%) 
Aortic injury  1  0/13756 (0.00%)  1/13769 (0.01%) 
Arterial bypass occlusion  1  1/13756 (0.01%)  1/13769 (0.01%) 
Arterial bypass thrombosis  1  0/13756 (0.00%)  1/13769 (0.01%) 
Arterial injury  1  1/13756 (0.01%)  0/13769 (0.00%) 
Arterial restenosis  1  1/13756 (0.01%)  0/13769 (0.00%) 
Arteriovenous fistula site complication  1  0/13756 (0.00%)  1/13769 (0.01%) 
Arthropod bite  1  1/13756 (0.01%)  1/13769 (0.01%) 
Avulsion fracture  1  1/13756 (0.01%)  0/13769 (0.00%) 
Back injury  1  0/13756 (0.00%)  2/13769 (0.01%) 
Carbon monoxide poisoning  1  1/13756 (0.01%)  0/13769 (0.00%) 
Carotid artery restenosis  1  0/13756 (0.00%)  1/13769 (0.01%) 
Cartilage injury  1  1/13756 (0.01%)  0/13769 (0.00%) 
Cervical vertebral fracture  1  1/13756 (0.01%)  4/13769 (0.03%) 
Chemical burn of gastrointestinal tract  1  1/13756 (0.01%)  0/13769 (0.00%) 
Chemical poisoning  1  0/13756 (0.00%)  1/13769 (0.01%) 
Chest injury  1  1/13756 (0.01%)  0/13769 (0.00%) 
Clavicle fracture  1  1/13756 (0.01%)  3/13769 (0.02%) 
Comminuted fracture  1  0/13756 (0.00%)  1/13769 (0.01%) 
Concussion  1  3/13756 (0.02%)  5/13769 (0.04%) 
Contusion  1  3/13756 (0.02%)  6/13769 (0.04%) 
Coronary artery restenosis  1  0/13756 (0.00%)  2/13769 (0.01%) 
Cranial nerve injury  1  0/13756 (0.00%)  1/13769 (0.01%) 
Craniocerebral injury  1  3/13756 (0.02%)  6/13769 (0.04%) 
Diffuse axonal injury  1  0/13756 (0.00%)  1/13769 (0.01%) 
Dislocation of sternum  1  0/13756 (0.00%)  1/13769 (0.01%) 
Dislocation of vertebra  1  0/13756 (0.00%)  1/13769 (0.01%) 
Endotracheal intubation complication  1  0/13756 (0.00%)  1/13769 (0.01%) 
Extradural haematoma  1  1/13756 (0.01%)  0/13769 (0.00%) 
Eye contusion  1  1/13756 (0.01%)  0/13769 (0.00%) 
Eye injury  1  2/13756 (0.01%)  1/13769 (0.01%) 
Eye operation complication  1  0/13756 (0.00%)  1/13769 (0.01%) 
Face injury  1  1/13756 (0.01%)  0/13769 (0.00%) 
Facial bones fracture  1  4/13756 (0.03%)  3/13769 (0.02%) 
Fall  1  13/13756 (0.09%)  17/13769 (0.12%) 
Femoral neck fracture  1  7/13756 (0.05%)  4/13769 (0.03%) 
Femur fracture  1  9/13756 (0.07%)  20/13769 (0.15%) 
Fibula fracture  1  0/13756 (0.00%)  1/13769 (0.01%) 
Foot fracture  1  4/13756 (0.03%)  5/13769 (0.04%) 
Forearm fracture  1  3/13756 (0.02%)  4/13769 (0.03%) 
Foreign body aspiration  1  1/13756 (0.01%)  0/13769 (0.00%) 
Fracture  1  2/13756 (0.01%)  1/13769 (0.01%) 
Fracture displacement  1  0/13756 (0.00%)  1/13769 (0.01%) 
Fractured ischium  1  0/13756 (0.00%)  1/13769 (0.01%) 
Fractured sacrum  1  1/13756 (0.01%)  0/13769 (0.00%) 
Graft complication  1  1/13756 (0.01%)  0/13769 (0.00%) 
Graft thrombosis  1  1/13756 (0.01%)  0/13769 (0.00%) 
Hand fracture  1  3/13756 (0.02%)  0/13769 (0.00%) 
Head injury  1  8/13756 (0.06%)  6/13769 (0.04%) 
Heat exhaustion  1  1/13756 (0.01%)  0/13769 (0.00%) 
Heat stroke  1  0/13756 (0.00%)  1/13769 (0.01%) 
Hip fracture  1  11/13756 (0.08%)  11/13769 (0.08%) 
Humerus fracture  1  8/13756 (0.06%)  6/13769 (0.04%) 
Ilium fracture  1  0/13756 (0.00%)  2/13769 (0.01%) 
Incisional hernia  1  4/13756 (0.03%)  5/13769 (0.04%) 
Incomplete spinal fusion  1  0/13756 (0.00%)  1/13769 (0.01%) 
Inflammation of wound  1  1/13756 (0.01%)  0/13769 (0.00%) 
Injury  1  2/13756 (0.01%)  5/13769 (0.04%) 
Intentional overdose  1  5/13756 (0.04%)  1/13769 (0.01%) 
Jaw fracture  1  1/13756 (0.01%)  0/13769 (0.00%) 
Joint dislocation  1  5/13756 (0.04%)  4/13769 (0.03%) 
Joint dislocation postoperative  1  0/13756 (0.00%)  2/13769 (0.01%) 
Joint injury  1  1/13756 (0.01%)  2/13769 (0.01%) 
Kidney contusion  1  1/13756 (0.01%)  0/13769 (0.00%) 
Laceration  1  4/13756 (0.03%)  4/13769 (0.03%) 
Ligament rupture  1  2/13756 (0.01%)  3/13769 (0.02%) 
Limb crushing injury  1  1/13756 (0.01%)  1/13769 (0.01%) 
Limb fracture  1  1/13756 (0.01%)  0/13769 (0.00%) 
Limb injury  1  3/13756 (0.02%)  2/13769 (0.01%) 
Limb traumatic amputation  1  1/13756 (0.01%)  4/13769 (0.03%) 
Lower limb fracture  1  3/13756 (0.02%)  3/13769 (0.02%) 
Lumbar vertebral fracture  1  4/13756 (0.03%)  7/13769 (0.05%) 
Medication error  1  1/13756 (0.01%)  0/13769 (0.00%) 
Meniscus injury  1  4/13756 (0.03%)  8/13769 (0.06%) 
Metal poisoning  1  1/13756 (0.01%)  0/13769 (0.00%) 
Multiple fractures  1  1/13756 (0.01%)  1/13769 (0.01%) 
Multiple injuries  1  2/13756 (0.01%)  0/13769 (0.00%) 
Muscle contusion  1  1/13756 (0.01%)  0/13769 (0.00%) 
Muscle rupture  1  1/13756 (0.01%)  0/13769 (0.00%) 
Neck injury  1  0/13756 (0.00%)  1/13769 (0.01%) 
Open globe injury  1  0/13756 (0.00%)  1/13769 (0.01%) 
Overdose  1  2/13756 (0.01%)  2/13769 (0.01%) 
Patella fracture  1  3/13756 (0.02%)  4/13769 (0.03%) 
Pelvic fracture  1  2/13756 (0.01%)  1/13769 (0.01%) 
Peripheral arterial reocclusion  1  0/13756 (0.00%)  2/13769 (0.01%) 
Peripheral artery restenosis  1  2/13756 (0.01%)  2/13769 (0.01%) 
Perirenal haematoma  1  0/13756 (0.00%)  1/13769 (0.01%) 
Peroneal nerve palsy postoperative  1  0/13756 (0.00%)  1/13769 (0.01%) 
Pneumoconiosis  1  0/13756 (0.00%)  1/13769 (0.01%) 
Pneumonitis chemical  1  0/13756 (0.00%)  1/13769 (0.01%) 
Pneumothorax traumatic  1  1/13756 (0.01%)  1/13769 (0.01%) 
Poisoning  1  1/13756 (0.01%)  0/13769 (0.00%) 
Post concussion syndrome  1  0/13756 (0.00%)  1/13769 (0.01%) 
Post laminectomy syndrome  1  1/13756 (0.01%)  0/13769 (0.00%) 
Post procedural complication  1  1/13756 (0.01%)  2/13769 (0.01%) 
Post procedural constipation  1  1/13756 (0.01%)  0/13769 (0.00%) 
Post procedural haematoma  1  3/13756 (0.02%)  3/13769 (0.02%) 
Post procedural haematuria  1  0/13756 (0.00%)  1/13769 (0.01%) 
Post procedural haemorrhage  1  7/13756 (0.05%)  6/13769 (0.04%) 
Post procedural myocardial infarction  1  2/13756 (0.01%)  0/13769 (0.00%) 
Post procedural swelling  1  1/13756 (0.01%)  1/13769 (0.01%) 
Post-traumatic neck syndrome  1  1/13756 (0.01%)  0/13769 (0.00%) 
Post-traumatic pain  1  0/13756 (0.00%)  1/13769 (0.01%) 
Postoperative respiratory failure  1  1/13756 (0.01%)  1/13769 (0.01%) 
Postoperative thoracic procedure complication  1  2/13756 (0.01%)  0/13769 (0.00%) 
Postoperative wound complication  1  1/13756 (0.01%)  0/13769 (0.00%) 
Procedural complication  1  1/13756 (0.01%)  0/13769 (0.00%) 
Procedural haemorrhage  1  1/13756 (0.01%)  1/13769 (0.01%) 
Procedural hypotension  1  1/13756 (0.01%)  0/13769 (0.00%) 
Procedural pain  1  1/13756 (0.01%)  2/13769 (0.01%) 
Procedural pneumothorax  1  3/13756 (0.02%)  0/13769 (0.00%) 
Pubis fracture  1  2/13756 (0.01%)  2/13769 (0.01%) 
Radial head dislocation  1  1/13756 (0.01%)  0/13769 (0.00%) 
Radiation mucositis  1  0/13756 (0.00%)  1/13769 (0.01%) 
Radiation oesophagitis  1  1/13756 (0.01%)  0/13769 (0.00%) 
Radius fracture  1  4/13756 (0.03%)  1/13769 (0.01%) 
Rib fracture  1  11/13756 (0.08%)  7/13769 (0.05%) 
Road traffic accident  1  6/13756 (0.04%)  4/13769 (0.03%) 
Sacroiliac fracture  1  0/13756 (0.00%)  1/13769 (0.01%) 
Scapula fracture  1  1/13756 (0.01%)  1/13769 (0.01%) 
Seroma  1  3/13756 (0.02%)  0/13769 (0.00%) 
Skeletal injury  1  0/13756 (0.00%)  1/13769 (0.01%) 
Skin abrasion  1  1/13756 (0.01%)  1/13769 (0.01%) 
Skull fracture  1  0/13756 (0.00%)  3/13769 (0.02%) 
Skull fractured base  1  1/13756 (0.01%)  0/13769 (0.00%) 
Snake bite  1  0/13756 (0.00%)  2/13769 (0.01%) 
Spinal column injury  1  1/13756 (0.01%)  1/13769 (0.01%) 
Spinal compression fracture  1  4/13756 (0.03%)  5/13769 (0.04%) 
Spinal cord injury  1  1/13756 (0.01%)  0/13769 (0.00%) 
Spinal cord injury lumbar  1  0/13756 (0.00%)  1/13769 (0.01%) 
Spinal fracture  1  3/13756 (0.02%)  2/13769 (0.01%) 
Splenic injury  1  1/13756 (0.01%)  0/13769 (0.00%) 
Stab wound  1  2/13756 (0.01%)  1/13769 (0.01%) 
Sternal fracture  1  0/13756 (0.00%)  2/13769 (0.01%) 
Subarachnoid haemorrhage  1  3/13756 (0.02%)  3/13769 (0.02%) 
Subcutaneous haematoma  1  0/13756 (0.00%)  1/13769 (0.01%) 
Subdural haematoma  1  11/13756 (0.08%)  6/13769 (0.04%) 
Subdural haemorrhage  1  2/13756 (0.01%)  3/13769 (0.02%) 
Tendon injury  1  0/13756 (0.00%)  2/13769 (0.01%) 
Tendon rupture  1  8/13756 (0.06%)  6/13769 (0.04%) 
Thermal burn  1  2/13756 (0.01%)  2/13769 (0.01%) 
Thoracic vertebral fracture  1  3/13756 (0.02%)  3/13769 (0.02%) 
Tibia fracture  1  2/13756 (0.01%)  7/13769 (0.05%) 
Toxicity to various agents  1  4/13756 (0.03%)  0/13769 (0.00%) 
Transplant failure  1  1/13756 (0.01%)  0/13769 (0.00%) 
Traumatic arthritis  1  0/13756 (0.00%)  1/13769 (0.01%) 
Traumatic fracture  1  1/13756 (0.01%)  0/13769 (0.00%) 
Traumatic haematoma  1  0/13756 (0.00%)  2/13769 (0.01%) 
Traumatic haemothorax  1  3/13756 (0.02%)  0/13769 (0.00%) 
Traumatic intracranial haemorrhage  1  0/13756 (0.00%)  1/13769 (0.01%) 
Traumatic shock  1  0/13756 (0.00%)  1/13769 (0.01%) 
Traumatic ulcer  1  0/13756 (0.00%)  1/13769 (0.01%) 
Ulna fracture  1  0/13756 (0.00%)  1/13769 (0.01%) 
Ulnar nerve injury  1  1/13756 (0.01%)  0/13769 (0.00%) 
Upper limb fracture  1  2/13756 (0.01%)  5/13769 (0.04%) 
Urethral stricture postoperative  1  0/13756 (0.00%)  1/13769 (0.01%) 
Vascular bypass dysfunction  1  2/13756 (0.01%)  1/13769 (0.01%) 
Vascular graft complication  1  1/13756 (0.01%)  0/13769 (0.00%) 
Vascular graft occlusion  1  5/13756 (0.04%)  2/13769 (0.01%) 
Vascular graft thrombosis  1  0/13756 (0.00%)  3/13769 (0.02%) 
Vascular procedure complication  1  1/13756 (0.01%)  0/13769 (0.00%) 
Vascular pseudoaneurysm  1  3/13756 (0.02%)  2/13769 (0.01%) 
Wound  1  3/13756 (0.02%)  2/13769 (0.01%) 
Wound dehiscence  1  1/13756 (0.01%)  4/13769 (0.03%) 
Wound evisceration  1  0/13756 (0.00%)  1/13769 (0.01%) 
Wound haemorrhage  1  1/13756 (0.01%)  0/13769 (0.00%) 
Wound necrosis  1  1/13756 (0.01%)  1/13769 (0.01%) 
Wound secretion  1  0/13756 (0.00%)  1/13769 (0.01%) 
Wrist fracture  1  1/13756 (0.01%)  3/13769 (0.02%) 
Investigations     
Alanine aminotransferase increased  1  15/13756 (0.11%)  11/13769 (0.08%) 
Arteriogram coronary  1  3/13756 (0.02%)  5/13769 (0.04%) 
Arteriogram coronary abnormal  1  2/13756 (0.01%)  1/13769 (0.01%) 
Arteriogram coronary normal  1  0/13756 (0.00%)  1/13769 (0.01%) 
Aspartate aminotransferase increased  1  11/13756 (0.08%)  6/13769 (0.04%) 
Blood alkaline phosphatase increased  1  1/13756 (0.01%)  0/13769 (0.00%) 
Blood bilirubin increased  1  1/13756 (0.01%)  0/13769 (0.00%) 
Blood creatine phosphokinase increased  1  6/13756 (0.04%)  7/13769 (0.05%) 
Blood creatinine increased  1  1/13756 (0.01%)  2/13769 (0.01%) 
Blood glucose decreased  1  1/13756 (0.01%)  0/13769 (0.00%) 
Blood glucose fluctuation  1  1/13756 (0.01%)  0/13769 (0.00%) 
Blood glucose increased  1  1/13756 (0.01%)  2/13769 (0.01%) 
Blood potassium increased  1  1/13756 (0.01%)  0/13769 (0.00%) 
Blood pressure increased  1  0/13756 (0.00%)  1/13769 (0.01%) 
Cardiac stress test abnormal  1  0/13756 (0.00%)  1/13769 (0.01%) 
Ejection fraction decreased  1  2/13756 (0.01%)  4/13769 (0.03%) 
Electrocardiogram QT prolonged  1  0/13756 (0.00%)  1/13769 (0.01%) 
Electrocardiogram ST segment depression  1  0/13756 (0.00%)  2/13769 (0.01%) 
Electrocardiogram abnormal  1  1/13756 (0.01%)  1/13769 (0.01%) 
Exercise electrocardiogram abnormal  1  0/13756 (0.00%)  1/13769 (0.01%) 
False positive investigation result  1  0/13756 (0.00%)  1/13769 (0.01%) 
Haemoglobin decreased  1  0/13756 (0.00%)  1/13769 (0.01%) 
Heart rate increased  1  1/13756 (0.01%)  0/13769 (0.00%) 
Heart rate irregular  1  1/13756 (0.01%)  0/13769 (0.00%) 
Hepatic enzyme increased  1  8/13756 (0.06%)  24/13769 (0.17%) 
Hepatitis A antibody positive  1  0/13756 (0.00%)  1/13769 (0.01%) 
Hepatitis A virus test positive  1  0/13756 (0.00%)  1/13769 (0.01%) 
Hepatitis B antibody positive  1  1/13756 (0.01%)  0/13769 (0.00%) 
Hepatitis C virus test positive  1  0/13756 (0.00%)  1/13769 (0.01%) 
Influenza A virus test positive  1  0/13756 (0.00%)  1/13769 (0.01%) 
Influenza B virus test positive  1  0/13756 (0.00%)  1/13769 (0.01%) 
International normalised ratio abnormal  1  0/13756 (0.00%)  1/13769 (0.01%) 
International normalised ratio increased  1  4/13756 (0.03%)  1/13769 (0.01%) 
Investigation  1  0/13756 (0.00%)  1/13769 (0.01%) 
Lipase increased  1  1/13756 (0.01%)  0/13769 (0.00%) 
Liver function test abnormal  1  4/13756 (0.03%)  7/13769 (0.05%) 
Liver function test increased  1  7/13756 (0.05%)  0/13769 (0.00%) 
Medical observation  1  0/13756 (0.00%)  1/13769 (0.01%) 
Myocardial necrosis marker increased  1  1/13756 (0.01%)  2/13769 (0.01%) 
Oxygen saturation decreased  1  1/13756 (0.01%)  0/13769 (0.00%) 
Precancerous cells present  1  1/13756 (0.01%)  0/13769 (0.00%) 
Stress echocardiogram  1  0/13756 (0.00%)  1/13769 (0.01%) 
Thyroid function test abnormal  1  0/13756 (0.00%)  1/13769 (0.01%) 
Transaminases increased  1  5/13756 (0.04%)  6/13769 (0.04%) 
Troponin I increased  1  2/13756 (0.01%)  1/13769 (0.01%) 
Troponin T increased  1  0/13756 (0.00%)  1/13769 (0.01%) 
Troponin increased  1  2/13756 (0.01%)  3/13769 (0.02%) 
Weight decreased  1  2/13756 (0.01%)  0/13769 (0.00%) 
Weight increased  1  0/13756 (0.00%)  1/13769 (0.01%) 
Metabolism and nutrition disorders     
Abnormal loss of weight  1  0/13756 (0.00%)  1/13769 (0.01%) 
Cachexia  1  1/13756 (0.01%)  0/13769 (0.00%) 
Decreased appetite  1  1/13756 (0.01%)  1/13769 (0.01%) 
Dehydration  1  18/13756 (0.13%)  16/13769 (0.12%) 
Diabetes mellitus  1  56/13756 (0.41%)  61/13769 (0.44%) 
Diabetes mellitus inadequate control  1  11/13756 (0.08%)  6/13769 (0.04%) 
Diabetic ketoacidosis  1  8/13756 (0.06%)  10/13769 (0.07%) 
Diabetic metabolic decompensation  1  3/13756 (0.02%)  2/13769 (0.01%) 
Electrolyte imbalance  1  1/13756 (0.01%)  3/13769 (0.02%) 
Fluid retention  1  1/13756 (0.01%)  0/13769 (0.00%) 
Glucose tolerance impaired  1  1/13756 (0.01%)  0/13769 (0.00%) 
Gout  1  5/13756 (0.04%)  6/13769 (0.04%) 
Hyperammonaemia  1  1/13756 (0.01%)  0/13769 (0.00%) 
Hypercalcaemia  1  2/13756 (0.01%)  0/13769 (0.00%) 
Hyperglycaemia  1  8/13756 (0.06%)  8/13769 (0.06%) 
Hyperinsulinaemic hypoglycaemia  1  0/13756 (0.00%)  1/13769 (0.01%) 
Hyperkalaemia  1  7/13756 (0.05%)  10/13769 (0.07%) 
Hypernatraemia  1  1/13756 (0.01%)  0/13769 (0.00%) 
Hyperosmolar hyperglycaemic state  1  0/13756 (0.00%)  1/13769 (0.01%) 
Hypocalcaemia  1  1/13756 (0.01%)  1/13769 (0.01%) 
Hypoglycaemia  1  11/13756 (0.08%)  17/13769 (0.12%) 
Hypoglycaemia unawareness  1  1/13756 (0.01%)  0/13769 (0.00%) 
Hypokalaemia  1  7/13756 (0.05%)  6/13769 (0.04%) 
Hypomagnesaemia  1  1/13756 (0.01%)  0/13769 (0.00%) 
Hyponatraemia  1  5/13756 (0.04%)  5/13769 (0.04%) 
Hypovitaminosis  1  0/13756 (0.00%)  1/13769 (0.01%) 
Hypovolaemia  1  1/13756 (0.01%)  2/13769 (0.01%) 
Ketoacidosis  1  1/13756 (0.01%)  0/13769 (0.00%) 
Malnutrition  1  2/13756 (0.01%)  0/13769 (0.00%) 
Metabolic acidosis  1  1/13756 (0.01%)  2/13769 (0.01%) 
Obesity  1  6/13756 (0.04%)  3/13769 (0.02%) 
Type 1 diabetes mellitus  1  1/13756 (0.01%)  0/13769 (0.00%) 
Type 2 diabetes mellitus  1  4/13756 (0.03%)  12/13769 (0.09%) 
Vitamin B12 deficiency  1  0/13756 (0.00%)  1/13769 (0.01%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  1  18/13756 (0.13%)  16/13769 (0.12%) 
Arthritis  1  13/13756 (0.09%)  11/13769 (0.08%) 
Arthropathy  1  3/13756 (0.02%)  4/13769 (0.03%) 
Back pain  1  30/13756 (0.22%)  30/13769 (0.22%) 
Bone deformity  1  1/13756 (0.01%)  0/13769 (0.00%) 
Bone pain  1  1/13756 (0.01%)  0/13769 (0.00%) 
Bursitis  1  2/13756 (0.01%)  3/13769 (0.02%) 
Cervical spinal stenosis  1  0/13756 (0.00%)  3/13769 (0.02%) 
Chondrocalcinosis pyrophosphate  1  0/13756 (0.00%)  1/13769 (0.01%) 
Chondropathy  1  0/13756 (0.00%)  2/13769 (0.01%) 
Costochondritis  1  3/13756 (0.02%)  1/13769 (0.01%) 
Diabetic amyotrophy  1  1/13756 (0.01%)  0/13769 (0.00%) 
Dupuytren's contracture  1  0/13756 (0.00%)  1/13769 (0.01%) 
Enthesopathy  1  1/13756 (0.01%)  0/13769 (0.00%) 
Exostosis  1  2/13756 (0.01%)  1/13769 (0.01%) 
Exostosis of jaw  1  1/13756 (0.01%)  0/13769 (0.00%) 
Facet joint syndrome  1  0/13756 (0.00%)  1/13769 (0.01%) 
Femoroacetabular impingement  1  1/13756 (0.01%)  0/13769 (0.00%) 
Fibromyalgia  1  1/13756 (0.01%)  0/13769 (0.00%) 
Flank pain  1  2/13756 (0.01%)  0/13769 (0.00%) 
Foot deformity  1  5/13756 (0.04%)  7/13769 (0.05%) 
Fracture nonunion  1  1/13756 (0.01%)  0/13769 (0.00%) 
Gouty arthritis  1  2/13756 (0.01%)  2/13769 (0.01%) 
Groin pain  1  1/13756 (0.01%)  0/13769 (0.00%) 
Intervertebral disc degeneration  1  3/13756 (0.02%)  8/13769 (0.06%) 
Intervertebral disc disorder  1  2/13756 (0.01%)  4/13769 (0.03%) 
Intervertebral disc displacement  1  1/13756 (0.01%)  1/13769 (0.01%) 
Intervertebral disc protrusion  1  24/13756 (0.17%)  22/13769 (0.16%) 
Jaw cyst  1  0/13756 (0.00%)  1/13769 (0.01%) 
Joint adhesion  1  1/13756 (0.01%)  0/13769 (0.00%) 
Joint effusion  1  2/13756 (0.01%)  1/13769 (0.01%) 
Joint instability  1  1/13756 (0.01%)  1/13769 (0.01%) 
Joint range of motion decreased  1  1/13756 (0.01%)  1/13769 (0.01%) 
Joint swelling  1  2/13756 (0.01%)  0/13769 (0.00%) 
Limb discomfort  1  0/13756 (0.00%)  1/13769 (0.01%) 
Lumbar spinal stenosis  1  17/13756 (0.12%)  21/13769 (0.15%) 
Mobility decreased  1  0/13756 (0.00%)  1/13769 (0.01%) 
Monarthritis  1  1/13756 (0.01%)  0/13769 (0.00%) 
Muscle spasms  1  0/13756 (0.00%)  1/13769 (0.01%) 
Muscular weakness  1  1/13756 (0.01%)  2/13769 (0.01%) 
Musculoskeletal chest pain  1  37/13756 (0.27%)  49/13769 (0.36%) 
Musculoskeletal pain  1  5/13756 (0.04%)  5/13769 (0.04%) 
Musculoskeletal stiffness  1  1/13756 (0.01%)  0/13769 (0.00%) 
Myalgia  1  2/13756 (0.01%)  8/13769 (0.06%) 
Myalgia intercostal  1  1/13756 (0.01%)  2/13769 (0.01%) 
Myofascitis  1  1/13756 (0.01%)  0/13769 (0.00%) 
Myopathy  1  0/13756 (0.00%)  2/13769 (0.01%) 
Myositis  1  0/13756 (0.00%)  1/13769 (0.01%) 
Neck pain  1  1/13756 (0.01%)  4/13769 (0.03%) 
Neuropathic arthropathy  1  0/13756 (0.00%)  1/13769 (0.01%) 
Nodal osteoarthritis  1  1/13756 (0.01%)  0/13769 (0.00%) 
Osteitis  1  0/13756 (0.00%)  1/13769 (0.01%) 
Osteoarthritis  1  100/13756 (0.73%)  91/13769 (0.66%) 
Osteochondritis  1  1/13756 (0.01%)  0/13769 (0.00%) 
Osteochondrosis  1  2/13756 (0.01%)  2/13769 (0.01%) 
Osteolysis  1  1/13756 (0.01%)  0/13769 (0.00%) 
Osteonecrosis  1  5/13756 (0.04%)  4/13769 (0.03%) 
Osteoporosis  1  1/13756 (0.01%)  0/13769 (0.00%) 
Osteoporotic fracture  1  0/13756 (0.00%)  2/13769 (0.01%) 
Pain in extremity  1  4/13756 (0.03%)  8/13769 (0.06%) 
Pain in jaw  1  0/13756 (0.00%)  1/13769 (0.01%) 
Patellofemoral pain syndrome  1  1/13756 (0.01%)  0/13769 (0.00%) 
Pathological fracture  1  0/13756 (0.00%)  1/13769 (0.01%) 
Periarthritis  1  2/13756 (0.01%)  2/13769 (0.01%) 
Polyarthritis  1  1/13756 (0.01%)  1/13769 (0.01%) 
Polymyalgia rheumatica  1  2/13756 (0.01%)  2/13769 (0.01%) 
Polymyositis  1  0/13756 (0.00%)  1/13769 (0.01%) 
Pseudarthrosis  1  1/13756 (0.01%)  0/13769 (0.00%) 
Psoriatic arthropathy  1  1/13756 (0.01%)  0/13769 (0.00%) 
Rhabdomyolysis  1  7/13756 (0.05%)  4/13769 (0.03%) 
Rheumatoid arthritis  1  2/13756 (0.01%)  3/13769 (0.02%) 
Rotator cuff syndrome  1