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Trial record 2 of 647 for:    Russian Federation | Chile

The Evaluation of Bococizumab (PF-04950615; RN316) in Reducing the Occurrence of Major Cardiovascular Events in High Risk Subjects (SPIRE-2)

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ClinicalTrials.gov Identifier: NCT01975389
Recruitment Status : Terminated (See Detailed Description)
First Posted : November 4, 2013
Results First Posted : June 12, 2018
Last Update Posted : May 1, 2019
Sponsor:
Information provided by (Responsible Party):
Pfizer

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Prevention
Condition Cardiovascular Disease
Interventions Drug: bococizumab (PF-04950615)
Drug: Placebo
Enrollment 10564
Recruitment Details  
Pre-assignment Details The trial was terminated prematurely on November 1, 2016, due to the emerging clinical profile and the evolving treatment and market landscape for lipid-lowering agents.
Arm/Group Title Placebo Bococizumab (PF-04950615)
Hide Arm/Group Description Participants received single dose of placebo matched to PF-04950615 subcutaneous injection once in every 2 weeks over a period of 3 years. Participants were followed up to 40 days after the last dose. Participants received single dose of PF-04950615, 150 milligrams, subcutaneous injection once in every 2 weeks over a period of 3 years. Participants were followed up to 40 days after the last dose.
Period Title: Overall Study
Started 5283 5281
Treated 5279 5276
Completed 5031 5045
Not Completed 252 236
Reason Not Completed
Adverse Event             10             6
Death             61             54
Lost to Follow-up             81             86
Withdrawal by Subject             90             76
Other             6             9
Randomized, not treated             4             5
Arm/Group Title Placebo Bococizumab (PF-04950615) Total
Hide Arm/Group Description Participants received single dose of placebo matched to PF-04950615 subcutaneous injection once in every 2 weeks over a period of 3 years. Participants were followed up to 40 days after the last dose. Participants received single dose of PF-04950615, 150 milligrams, subcutaneous injection once in every 2 weeks over a period of 3 years. Participants were followed up to 40 days after the last dose. Total of all reporting groups
Overall Number of Baseline Participants 5283 5281 10564
Hide Baseline Analysis Population Description
Full analysis set (FAS): all participants who were randomized, excluding who attempted to be randomized more than once into a bococizumab cardiovascular (CV) outcomes trial (B1481022/B1481038) or attempted to be randomized in more than 1 CV outcomes trial and all participants enrolled at study Site 3027 where a quality-related event was identified.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 5283 participants 5281 participants 10564 participants
62.5  (9.5) 62.2  (9.6) 62.4  (9.6)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 5283 participants 5281 participants 10564 participants
Female
1849
  35.0%
1792
  33.9%
3641
  34.5%
Male
3434
  65.0%
3489
  66.1%
6923
  65.5%
Ethnicity (NIH/OMB)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 5283 participants 5281 participants 10564 participants
Hispanic or Latino
852
  16.1%
892
  16.9%
1744
  16.5%
Not Hispanic or Latino
4430
  83.9%
4387
  83.1%
8817
  83.5%
Unknown or Not Reported
1
   0.0%
2
   0.0%
3
   0.0%
[1]
Measure Analysis Population Description: Full analysis set (FAS): all participants who were randomized, excluding who attempted to be randomized more than once into a bococizumab cardiovascular (CV) outcomes trial (B1481022/B1481038) or attempted to be randomized in more than 1 CV outcomes trial and all participants enrolled at study Site 3027 where a quality-related event was identified.
Race (NIH/OMB)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 5283 participants 5281 participants 10564 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
118
   2.2%
105
   2.0%
223
   2.1%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
246
   4.7%
252
   4.8%
498
   4.7%
White
4776
  90.4%
4784
  90.6%
9560
  90.5%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
143
   2.7%
140
   2.7%
283
   2.7%
[1]
Measure Analysis Population Description: FAS: all participants who were randomized, excluding who attempted to be randomized more than once into a bococizumab cardiovascular (CV) outcomes trial (B1481022/B1481038) or attempted to be randomized in more than 1 CV outcomes trial and all participants enrolled at study Site 3027 where a quality-related event was identified.
1.Primary Outcome
Title Event Rate Per 100 Participant-years for First Occurrence of Major Cardiovascular (CV) Event
Hide Description Event rate per 100 participant-years for first occurrence of major CV event (adjudicated by Adjudication Committee) was reported. Major CV event was defined as any of the following: CV death [defined as sudden cardiac death, fatal myocardial infarction (MI), death due to heart failure, death due to stroke (fatal ischemic stroke or fatal stroke of undetermined etiology), or death due to other CV causes] non-fatal MI, non-fatal stroke, and hospitalization for unstable angina needing urgent revascularization. Event rate was calculated as the number of events per 100 participant-years at risk.
Time Frame From baseline until the date of first adjudicated and confirmed occurrence of major CV event (maximum duration: up to 3.4 years)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS: all participants who were randomized, excluding who attempted to be randomized more than once into a bococizumab CV outcomes trial (B1481022/B1481038) or attempted to be randomized in more than 1 CV outcomes trial and all participants enrolled at study Site 3027 where a quality-related event was identified.
Arm/Group Title Placebo Bococizumab (PF-04950615)
Hide Arm/Group Description:
Participants received single dose of placebo matched to PF-04950615 subcutaneous injection once in every 2 weeks over a period of 3 years. Participants were followed up to 40 days after the last dose.
Participants received single dose of PF-04950615, 150 milligrams, subcutaneous injection once in every 2 weeks over a period of 3 years. Participants were followed up to 40 days after the last dose.
Overall Number of Participants Analyzed 5283 5281
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Events per 100 participant-years
4.19
(3.66 to 4.78)
3.33
(2.86 to 3.86)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Bococizumab (PF-04950615)
Comments Hazard ratio and 95% Confidence Interval (CI) were obtained from a Cox proportional hazards model stratified by geographic region and complete statin intolerance with treatment as a covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.021469
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.79
Confidence Interval (2-Sided) 95%
0.65 to 0.97
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Event Rate Per 100 Participant-years for First Occurrence of Composite Endpoint of Cardiovascular (CV) Death, Non-fatal Myocardial Infraction (MI) or Non-fatal Stroke
Hide Description Event rate per 100 participant-years for first occurrence of composite endpoint of CV Death, non-fatal MI or non-fatal stroke (adjudicated by Adjudication Committee) was reported. CV death was defined as sudden cardiac death, fatal MI, death due to heart failure, death due to stroke (fatal ischemic stroke or fatal stroke of undetermined etiology), or death due to other CV causes. Event rate was calculated as the number of events per 100 participant-years at risk.
Time Frame From baseline until the date of first adjudicated and confirmed occurrence of CV death, non-fatal MI or non-fatal stroke (maximum duration: up to 3.4 years)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS: all participants who were randomized, excluding who attempted to be randomized more than once into a bococizumab CV outcomes trial (B1481022/B1481038) or attempted to be randomized in more than 1 CV outcomes trial and all participants enrolled at study Site 3027 where a quality-related event was identified.
Arm/Group Title Placebo Bococizumab (PF-04950615)
Hide Arm/Group Description:
Participants received single dose of placebo matched to PF-04950615 subcutaneous injection once in every 2 weeks over a period of 3 years. Participants were followed up to 40 days after the last dose.
Participants received single dose of PF-04950615, 150 milligrams, subcutaneous injection once in every 2 weeks over a period of 3 years. Participants were followed up to 40 days after the last dose.
Overall Number of Participants Analyzed 5283 5281
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Events per 100 participant-years
3.58
(3.09 to 4.12)
2.67
(2.25 to 3.14)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Bococizumab (PF-04950615)
Comments Hazard ratio and 95% CI were obtained from a Cox proportional hazards model stratified by geographic region and complete statin intolerance with treatment as a covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.007597
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.75
Confidence Interval (2-Sided) 95%
0.60 to 0.93
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Event Rate Per 100 Participant-years for First Occurrence of Composite Endpoint of All-cause Death, Non-fatal Myocardial Infraction (MI), Non-fatal Stroke or Hospitalization for Unstable Angina Needing Urgent Revascularization
Hide Description Event rate per 100 participant-years for first occurrence of composite endpoint of all-cause death, non-fatal MI, non-fatal stroke or hospitalization for unstable angina needing urgent revascularization (adjudicated by Adjudication Committee) was reported. All-cause death was defined as the death due to any cause during the course of study. Event rate was calculated as the number of events per 100 participant-years at risk.
Time Frame From baseline until the date of first adjudicated and confirmed occurrence of all-cause death, non-fatal MI, non-fatal stroke or hospitalization for unstable angina needing urgent revascularization (maximum duration: up to 3.4 years)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS: all participants who were randomized, excluding who attempted to be randomized more than once into a bococizumab CV outcomes trial (B1481022/B1481038) or attempted to be randomized in more than 1 CV outcomes trial and all participants enrolled at study Site 3027 where a quality-related event was identified.
Arm/Group Title Placebo Bococizumab (PF-04950615)
Hide Arm/Group Description:
Participants received single dose of placebo matched to PF-04950615 subcutaneous injection once in every 2 weeks over a period of 3 years. Participants were followed up to 40 days after the last dose.
Participants received single dose of PF-04950615, 150 milligrams, subcutaneous injection once in every 2 weeks over a period of 3 years. Participants were followed up to 40 days after the last dose.
Overall Number of Participants Analyzed 5283 5281
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Events per 100 participant-years
4.59
(4.03 to 5.20)
3.76
(3.26 to 4.32)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Bococizumab (PF-04950615)
Comments Hazard ratio and 95% CI were obtained from a Cox proportional hazards model stratified by geographic region and complete statin intolerance with treatment as a covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.035958
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.82
Confidence Interval (2-Sided) 95%
0.68 to 0.99
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Event Rate Per 100 Participant-years for First Occurrence of Composite Endpoint of All-cause Death, Non-fatal Myocardial Infarction (MI) or Non-fatal Stroke
Hide Description Event rate per 100 participant-years for first occurrence of composite endpoint of all-cause death, non-fatal MI or non-fatal stroke (adjudicated by Adjudication Committee) was reported. All-cause death was defined as the death due to any cause during the course of study. Event rate was calculated as the number of events per 100 participant-years at risk.
Time Frame From baseline until the date of first adjudicated and confirmed occurrence of all-cause death, non-fatal MI or non-fatal stroke (maximum duration: up to 3.4 years)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS: all participants who were randomized, excluding who attempted to be randomized more than once into a bococizumab CV outcomes trial (B1481022/B1481038) or attempted to be randomized in more than 1 CV outcomes trial and all participants enrolled at study Site 3027 where a quality-related event was identified.
Arm/Group Title Placebo Bococizumab (PF-04950615)
Hide Arm/Group Description:
Participants received single dose of placebo matched to PF-04950615 subcutaneous injection once in every 2 weeks over a period of 3 years. Participants were followed up to 40 days after the last dose.
Participants received single dose of PF-04950615, 150 milligrams, subcutaneous injection once in every 2 weeks over a period of 3 years. Participants were followed up to 40 days after the last dose.
Overall Number of Participants Analyzed 5283 5281
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Events per 100 participant-years
3.97
(3.45 to 4.54)
3.09
(2.64 to 3.60)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Bococizumab (PF-04950615)
Comments Hazard ratio and 95% CI were obtained from a Cox proportional hazards model stratified by geographic region and complete statin intolerance with treatment as a covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.015694
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.78
Confidence Interval (2-Sided) 95%
0.64 to 0.95
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Event Rate Per 100 Participant-years for First Occurrence of Hospitalization for Unstable Angina Needing Urgent Revascularization
Hide Description Event rate per 100 participant-years for first occurrence of hospitalization for unstable angina needing urgent revascularization (adjudicated by Adjudication Committee) was reported. Event rate was calculated as the number of events per 100 participant-years at risk.
Time Frame From baseline until the date of first adjudicated and confirmed occurrence of hospitalization for unstable angina needing urgent revascularization (maximum duration: up to 3.4 years)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS: all participants who were randomized, excluding who attempted to be randomized more than once into a bococizumab CV outcomes trial (B1481022/B1481038) or attempted to be randomized in more than 1 CV outcomes trial and all participants enrolled at study Site 3027 where a quality-related event was identified.
Arm/Group Title Placebo Bococizumab (PF-04950615)
Hide Arm/Group Description:
Participants received single dose of placebo matched to PF-04950615 subcutaneous injection once in every 2 weeks over a period of 3 years. Participants were followed up to 40 days after the last dose.
Participants received single dose of PF-04950615, 150 milligrams, subcutaneous injection once in every 2 weeks over a period of 3 years. Participants were followed up to 40 days after the last dose.
Overall Number of Participants Analyzed 5283 5281
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Events per 100 participant-years
0.77
(0.56 to 1.05)
0.73
(0.52 to 1.00)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Bococizumab (PF-04950615)
Comments Hazard ratio and 95% CI were obtained from a Cox proportional hazards model stratified by geographic region and complete statin intolerance with treatment as a covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.814224
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.95
Confidence Interval (2-Sided) 95%
0.62 to 1.46
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Event Rate Per 100 Participant-years for First Occurrence of Composite Endpoint of Cardiovascular (CV) Death, Non-fatal Myocardial Infarction (MI), Non-fatal Stroke or Hospitalization for Unstable Angina
Hide Description Event rate per 100 participant-years for first occurrence of composite endpoint of CV death, non-fatal MI, non-fatal stroke or hospitalization for unstable angina (adjudicated by Adjudication Committee) was reported. CV death was defined as sudden cardiac death, fatal MI, death due to heart failure, death due to stroke (fatal ischemic stroke or fatal stroke of undetermined etiology), or death due to other CV causes. Event rate was calculated as the number of events per 100 participant-years at risk.
Time Frame From baseline until the date of first adjudicated and confirmed occurrence of CV death, non-fatal MI, non-fatal stroke or hospitalization for unstable angina (maximum duration: up to 3.4 years)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS: all participants who were randomized, excluding who attempted to be randomized more than once into a bococizumab CV outcomes trial (B1481022/B1481038) or attempted to be randomized in more than 1 CV outcomes trial and all participants enrolled at study Site 3027 where a quality-related event was identified.
Arm/Group Title Placebo Bococizumab (PF-04950615)
Hide Arm/Group Description:
Participants received single dose of placebo matched to PF-04950615 subcutaneous injection once in every 2 weeks over a period of 3 years. Participants were followed up to 40 days after the last dose.
Participants received single dose of PF-04950615, 150 milligrams, subcutaneous injection once in every 2 weeks over a period of 3 years. Participants were followed up to 40 days after the last dose.
Overall Number of Participants Analyzed 5283 5281
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Events per 100 participant-years
4.35
(3.81 to 4.94)
3.45
(2.97 to 3.98)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Bococizumab (PF-04950615)
Comments Hazard ratio and 95% CI were obtained from a Cox proportional hazards model stratified by geographic region and complete statin intolerance with treatment as a covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.018053
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.79
Confidence Interval (2-Sided) 95%
0.65 to 0.96
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Event Rate Per 100 Participant-years for Cardiovascular (CV) Death
Hide Description Event rate per 100 participant-years for occurrence of CV death (adjudicated by Adjudication Committee) was reported. CV death was defined as sudden cardiac death, fatal MI, death due to heart failure, death due to stroke (fatal ischemic stroke or fatal stroke of undetermined etiology), or death due to other CV causes. Event rate was calculated as the number of events per 100 participant-years at risk.
Time Frame From baseline until the date of adjudicated and confirmed occurrence of CV death (maximum duration: up to 3.4 years)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS: all participants who were randomized, excluding who attempted to be randomized more than once into a bococizumab CV outcomes trial (B1481022/B1481038) or attempted to be randomized in more than 1 CV outcomes trial and all participants enrolled at study Site 3027 where a quality-related event was identified.
Arm/Group Title Placebo Bococizumab (PF-04950615)
Hide Arm/Group Description:
Participants received single dose of placebo matched to PF-04950615 subcutaneous injection once in every 2 weeks over a period of 3 years. Participants were followed up to 40 days after the last dose.
Participants received single dose of PF-04950615, 150 milligrams, subcutaneous injection once in every 2 weeks over a period of 3 years. Participants were followed up to 40 days after the last dose.
Overall Number of Participants Analyzed 5283 5281
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Events per 100 participant-years
0.62
(0.43 to 0.87)
0.51
(0.34 to 0.74)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Bococizumab (PF-04950615)
Comments Hazard ratio and 95% CI were obtained from a Cox proportional hazards model stratified by geographic region and complete statin intolerance with treatment as a covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.446033
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.82
Confidence Interval (2-Sided) 95%
0.50 to 1.36
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Event Rate Per 100 Participant-years for First Occurrence of Any Myocardial Infarction (Fatal or Non-fatal)
Hide Description Event rate per 100 participant-years for first occurrence of any myocardial infarction (fatal or non-fatal) (adjudicated by Adjudication Committee) was reported. Event rate was calculated as the number of events per 100 participant-years at risk.
Time Frame From baseline until the date of first adjudicated and confirmed occurrence of any myocardial infarction (fatal or non-fatal) (maximum duration: up to 3.4 years)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS: all participants who were randomized, excluding who attempted to be randomized more than once into a bococizumab CV outcomes trial (B1481022/B1481038) or attempted to be randomized in more than 1 CV outcomes trial and all participants enrolled at study Site 3027 where a quality-related event was identified.
Arm/Group Title Placebo Bococizumab (PF-04950615)
Hide Arm/Group Description:
Participants received single dose of placebo matched to PF-04950615 subcutaneous injection once in every 2 weeks over a period of 3 years. Participants were followed up to 40 days after the last dose.
Participants received single dose of PF-04950615, 150 milligrams, subcutaneous injection once in every 2 weeks over a period of 3 years. Participants were followed up to 40 days after the last dose.
Overall Number of Participants Analyzed 5283 5281
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Events per 100 participant-years
2.39
(2.00 to 2.84)
1.79
(1.45 to 2.19)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Bococizumab (PF-04950615)
Comments Hazard ratio and 95% CI were obtained from a Cox proportional hazards model stratified by geographic region and complete statin intolerance with treatment as a covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.029977
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.75
Confidence Interval (2-Sided) 95%
0.57 to 0.97
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Event Rate Per 100 Participant-years for Fatal Myocardial Infarction (MI)
Hide Description Event rate per 100 participant-years for occurrence of fatal MI (adjudicated by Adjudication Committee) was reported. Event rate was calculated as the number of events per 100 participant-years at risk.
Time Frame From baseline until the date of adjudicated and confirmed occurrence of fatal MI (maximum duration: up to 3.4 years)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS: all participants who were randomized, excluding who attempted to be randomized more than once into a bococizumab CV outcomes trial (B1481022/B1481038) or attempted to be randomized in more than 1 CV outcomes trial and all participants enrolled at study Site 3027 where a quality-related event was identified.
Arm/Group Title Placebo Bococizumab (PF-04950615)
Hide Arm/Group Description:
Participants received single dose of placebo matched to PF-04950615 subcutaneous injection once in every 2 weeks over a period of 3 years. Participants were followed up to 40 days after the last dose.
Participants received single dose of PF-04950615, 150 milligrams, subcutaneous injection once in every 2 weeks over a period of 3 years. Participants were followed up to 40 days after the last dose.
Overall Number of Participants Analyzed 5283 5281
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Events per 100 participant-years
0.16
(0.08 to 0.31)
0.07
(0.02 to 0.19)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Bococizumab (PF-04950615)
Comments Hazard ratio and 95% CI were obtained from a Cox proportional hazards model stratified by geographic region and complete statin intolerance with treatment as a covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.162615
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.44
Confidence Interval (2-Sided) 95%
0.14 to 1.44
Estimation Comments [Not Specified]
10.Secondary Outcome
Title Event Rate Per 100 Participant-years for First Occurrence of Non-fatal Myocardial Infarction (MI)
Hide Description Event rate per 100 participant-years for first occurrence of non-fatal MI (adjudicated by Adjudication Committee) was reported. Event rate was calculated as the number of events per 100 participant-years at risk.
Time Frame From baseline until the date of first adjudicated and confirmed occurrence of non-fatal MI (maximum duration: up to 3.4 years)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS: all participants who were randomized, excluding who attempted to be randomized more than once into a bococizumab CV outcomes trial (B1481022/B1481038) or attempted to be randomized in more than 1 CV outcomes trial and all participants enrolled at study Site 3027 where a quality-related event was identified.
Arm/Group Title Placebo Bococizumab (PF-04950615)
Hide Arm/Group Description:
Participants received single dose of placebo matched to PF-04950615 subcutaneous injection once in every 2 weeks over a period of 3 years. Participants were followed up to 40 days after the last dose.
Participants received single dose of PF-04950615, 150 milligrams, subcutaneous injection once in every 2 weeks over a period of 3 years. Participants were followed up to 40 days after the last dose.
Overall Number of Participants Analyzed 5283 5281
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Events per 100 participant-years
2.26
(1.88 to 2.70)
1.74
(1.40 to 2.12)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Bococizumab (PF-04950615)
Comments Hazard ratio and 95% CI were obtained from a Cox proportional hazards model stratified by geographic region and complete statin intolerance with treatment as a covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.051534
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.77
Confidence Interval (2-Sided) 95%
0.59 to 1.00
Estimation Comments [Not Specified]
11.Secondary Outcome
Title Event Rate Per 100 Participant-years for First Occurrence of Any Stroke (Fatal or Non-fatal)
Hide Description Event rate per 100 participant-years for first occurrence of any stroke (fatal or non-fatal) (adjudicated by Adjudication Committee) was reported. Event rate was calculated as the number of events per 100 participant-years at risk.
Time Frame From baseline until the date of first adjudicated and confirmed occurrence of any stroke (fatal or non-fatal) (maximum duration: up to 3.4 years)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS: all participants who were randomized, excluding who attempted to be randomized more than once into a bococizumab CV outcomes trial (B1481022/B1481038) or attempted to be randomized in more than 1 CV outcomes trial and all participants enrolled at study Site 3027 where a quality-related event was identified.
Arm/Group Title Placebo Bococizumab (PF-04950615)
Hide Arm/Group Description:
Participants received single dose of placebo matched to PF-04950615 subcutaneous injection once in every 2 weeks over a period of 3 years. Participants were followed up to 40 days after the last dose.
Participants received single dose of PF-04950615, 150 milligrams, subcutaneous injection once in every 2 weeks over a period of 3 years. Participants were followed up to 40 days after the last dose.
Overall Number of Participants Analyzed 5283 5281
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Events per 100 participant-years
0.72
(0.51 to 0.98)
0.48
(0.31 to 0.70)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Bococizumab (PF-04950615)
Comments Hazard ratio and 95% CI were obtained from a Cox proportional hazards model stratified by geographic region and complete statin intolerance with treatment as a covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.104998
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.67
Confidence Interval (2-Sided) 95%
0.41 to 1.09
Estimation Comments [Not Specified]
12.Secondary Outcome
Title Event Rate Per 100 Participant-years for First Occurrence of Any Stroke (Fatal or Non-fatal), of Any Etiology
Hide Description Event rate per 100 participant-years for first occurrence of any stroke (fatal or non-fatal) of any etiology (adjudicated by Adjudication Committee) was reported. Event rate was calculated as the number of events per 100 participant-years at risk.
Time Frame From baseline until the date of first adjudicated and confirmed occurrence of any stroke (fatal or non-fatal) of any etiology (maximum duration: up to 3.4 years)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS: all participants who were randomized, excluding who attempted to be randomized more than once into a bococizumab CV outcomes trial (B1481022/B1481038) or attempted to be randomized in more than 1 CV outcomes trial and all participants enrolled at study Site 3027 where a quality-related event was identified.
Arm/Group Title Placebo Bococizumab (PF-04950615)
Hide Arm/Group Description:
Participants received single dose of placebo matched to PF-04950615 subcutaneous injection once in every 2 weeks over a period of 3 years. Participants were followed up to 40 days after the last dose.
Participants received single dose of PF-04950615, 150 milligrams, subcutaneous injection once in every 2 weeks over a period of 3 years. Participants were followed up to 40 days after the last dose.
Overall Number of Participants Analyzed 5283 5281
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Events per 100 participant-years
0.77
(0.56 to 1.04)
0.61
(0.42 to 0.85)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Bococizumab (PF-04950615)
Comments Hazard ratio and 95% CI were obtained from a Cox proportional hazards model stratified by geographic region and complete statin intolerance with treatment as a covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.294331
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.78
Confidence Interval (2-Sided) 95%
0.50 to 1.24
Estimation Comments [Not Specified]
13.Secondary Outcome
Title Event Rate Per 100 Participant-years for Fatal Stroke
Hide Description Event rate per 100 participant-years for occurrence of fatal stroke (adjudicated by Adjudication Committee) was reported. Event rate was calculated as the number of events per 100 participant-years at risk.
Time Frame From baseline until the date of adjudicated and confirmed occurrence of fatal stroke (maximum duration: up to 3.4 years)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS: all participants who were randomized, excluding who attempted to be randomized more than once into a bococizumab CV outcomes trial (B1481022/B1481038) or attempted to be randomized in more than 1 CV outcomes trial and all participants enrolled at study Site 3027 where a quality-related event was identified.
Arm/Group Title Placebo Bococizumab (PF-04950615)
Hide Arm/Group Description:
Participants received single dose of placebo matched to PF-04950615 subcutaneous injection once in every 2 weeks over a period of 3 years. Participants were followed up to 40 days after the last dose.
Participants received single dose of PF-04950615, 150 milligrams, subcutaneous injection once in every 2 weeks over a period of 3 years. Participants were followed up to 40 days after the last dose.
Overall Number of Participants Analyzed 5283 5281
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Events per 100 participant-years
0.00
(0.00 to 0.05)
0.00
(0.00 to 0.05)
14.Secondary Outcome
Title Event Rate Per 100 Participant-years for First Occurrence of Non-fatal Stroke
Hide Description Event rate per 100 participant-years for first occurrence of non-fatal stroke (adjudicated by Adjudication Committee) was reported. Event rate was calculated as the number of events per 100 participant-years at risk.
Time Frame From baseline until the date of first adjudicated and confirmed occurrence of non-fatal stroke (maximum duration: up to 3.4 years)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS: all participants who were randomized, excluding who attempted to be randomized more than once into a bococizumab CV outcomes trial (B1481022/B1481038) or attempted to be randomized in more than 1 CV outcomes trial and all participants enrolled at study Site 3027 where a quality-related event was identified.
Arm/Group Title Placebo Bococizumab (PF-04950615)
Hide Arm/Group Description:
Participants received single dose of placebo matched to PF-04950615 subcutaneous injection once in every 2 weeks over a period of 3 years. Participants were followed up to 40 days after the last dose.
Participants received single dose of PF-04950615, 150 milligrams, subcutaneous injection once in every 2 weeks over a period of 3 years. Participants were followed up to 40 days after the last dose.
Overall Number of Participants Analyzed 5283 5281
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Events per 100 participant-years
0.72
(0.51 to 0.98)
0.48
(0.31 to 0.70)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Bococizumab (PF-04950615)
Comments Hazard ratio and 95% CI were obtained from a Cox proportional hazards model stratified by geographic region and complete statin intolerance with treatment as a covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.104998
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.67
Confidence Interval (2-Sided) 95%
0.41 to 1.09
Estimation Comments [Not Specified]
15.Secondary Outcome
Title Event Rate Per 100 Participant-years for First Occurrence of Hospitalization for Unstable Angina
Hide Description Event rate per 100 participant-years for first occurrence of hospitalization for unstable angina (adjudicated by Adjudication Committee) was reported. Event rate was calculated as the number of events per 100 participant-years at risk.
Time Frame From baseline until the date of first adjudicated and confirmed occurrence of hospitalization for unstable angina (maximum duration: up to 3.4 years)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS: all participants who were randomized, excluding who attempted to be randomized more than once into a bococizumab CV outcomes trial (B1481022/B1481038) or attempted to be randomized in more than 1 CV outcomes trial and all participants enrolled at study Site 3027 where a quality-related event was identified.
Arm/Group Title Placebo Bococizumab (PF-04950615)
Hide Arm/Group Description:
Participants received single dose of placebo matched to PF-04950615 subcutaneous injection once in every 2 weeks over a period of 3 years. Participants were followed up to 40 days after the last dose.
Participants received single dose of PF-04950615, 150 milligrams, subcutaneous injection once in every 2 weeks over a period of 3 years. Participants were followed up to 40 days after the last dose.
Overall Number of Participants Analyzed 5283 5281
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Events per 100 participant-years
0.94
(0.70 to 1.24)
0.85
(0.62 to 1.13)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Bococizumab (PF-04950615)
Comments Hazard ratio and 95% CI were obtained from a Cox proportional hazards model stratified by geographic region and complete statin intolerance with treatment as a covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.601200
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.90
Confidence Interval (2-Sided) 95%
0.60 to 1.34
Estimation Comments [Not Specified]
16.Secondary Outcome
Title Event Rate Per 100 Participant-years for First Occurrence of Hospitalization for Congestive Heart Failure (CHF)
Hide Description Event rate per 100 participant-years for first occurrence of hospitalization for CHF (adjudicated by Adjudication Committee) was reported. Event rate was calculated as the number of events per 100 participant-years at risk.
Time Frame From baseline until the date of first adjudicated and confirmed occurrence of hospitalization for CHF (maximum duration: up to 3.4 years)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS: all participants who were randomized, excluding who attempted to be randomized more than once into a bococizumab CV outcomes trial (B1481022/B1481038) or attempted to be randomized in more than 1 CV outcomes trial and all participants enrolled at study Site 3027 where a quality-related event was identified.
Arm/Group Title Placebo Bococizumab (PF-04950615)
Hide Arm/Group Description:
Participants received single dose of placebo matched to PF-04950615 subcutaneous injection once in every 2 weeks over a period of 3 years. Participants were followed up to 40 days after the last dose.
Participants received single dose of PF-04950615, 150 milligrams, subcutaneous injection once in every 2 weeks over a period of 3 years. Participants were followed up to 40 days after the last dose.
Overall Number of Participants Analyzed 5283 5281
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Events per 100 participant-years
0.75
(0.54 to 1.02)
0.83
(0.60 to 1.11)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Bococizumab (PF-04950615)
Comments Hazard ratio and 95% CI were obtained from a Cox proportional hazards model stratified by geographic region and complete statin intolerance with treatment as a covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.678061
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.09
Confidence Interval (2-Sided) 95%
0.72 to 1.67
Estimation Comments [Not Specified]
17.Secondary Outcome
Title Event Rate Per 100 Participant-years for First Occurrence of Coronary Revascularization
Hide Description Event rate per 100 participant-years for first occurrence of coronary revascularization (adjudicated by Adjudication Committee) was reported. Event rate was calculated as the number of events per 100 participant-years at risk.
Time Frame From baseline until the date of first adjudicated and confirmed occurrence of coronary revascularization (maximum duration: up to 3.4 years)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS: all participants who were randomized, excluding who attempted to be randomized more than once into a bococizumab CV outcomes trial (B1481022/B1481038) or attempted to be randomized in more than 1 CV outcomes trial and all participants enrolled at study Site 3027 where a quality-related event was identified.
Arm/Group Title Placebo Bococizumab (PF-04950615)
Hide Arm/Group Description:
Participants received single dose of placebo matched to PF-04950615 subcutaneous injection once in every 2 weeks over a period of 3 years. Participants were followed up to 40 days after the last dose.
Participants received single dose of PF-04950615, 150 milligrams, subcutaneous injection once in every 2 weeks over a period of 3 years. Participants were followed up to 40 days after the last dose.
Overall Number of Participants Analyzed 5283 5281
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Events per 100 participant-years
4.18
(3.65 to 4.77)
3.23
(2.76 to 3.75)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Bococizumab (PF-04950615)
Comments Hazard ratio and 95% CI were obtained from a Cox proportional hazards model stratified by geographic region and complete statin intolerance with treatment as a covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.010457
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.77
Confidence Interval (2-Sided) 95%
0.63 to 0.94
Estimation Comments [Not Specified]
18.Secondary Outcome
Title Event Rate Per 100 Participant-years for First Occurrence of Coronary Artery Bypass Graft Surgery (CABG)
Hide Description Event rate per 100 participant-years for first occurrence of CABG (adjudicated by Adjudication Committee) was reported. Event rate was calculated as the number of events per 100 participant-years at risk.
Time Frame From baseline until the date of first adjudicated and confirmed occurrence of CABG (maximum duration: up to 3.4 years)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS: all participants who were randomized, excluding who attempted to be randomized more than once into a bococizumab CV outcomes trial (B1481022/B1481038) or attempted to be randomized in more than 1 CV outcomes trial and all participants enrolled at study Site 3027 where a quality-related event was identified.
Arm/Group Title Placebo Bococizumab (PF-04950615)
Hide Arm/Group Description:
Participants received single dose of placebo matched to PF-04950615 subcutaneous injection once in every 2 weeks over a period of 3 years. Participants were followed up to 40 days after the last dose.
Participants received single dose of PF-04950615, 150 milligrams, subcutaneous injection once in every 2 weeks over a period of 3 years. Participants were followed up to 40 days after the last dose.
Overall Number of Participants Analyzed 5283 5281
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Events per 100 participant-years
0.48
(0.31 to 0.70)
0.57
(0.39 to 0.81)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Bococizumab (PF-04950615)
Comments Hazard ratio and 95% CI were obtained from a Cox proportional hazards model stratified by geographic region and complete statin intolerance with treatment as a covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.509847
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.19
Confidence Interval (2-Sided) 95%
0.71 to 2.01
Estimation Comments [Not Specified]
19.Secondary Outcome
Title Event Rate Per 100 Participant-years for First Occurrence of Percutaneous Coronary Intervention (PCI)
Hide Description Event rate per 100 participant-years for first occurrence of PCI (adjudicated by Adjudication Committee) was reported. Event rate was calculated as the number of events per 100 participant-years at risk.
Time Frame From baseline until the date of first adjudicated and confirmed occurrence of PCI (maximum duration: up to 3.4 years)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS: all participants who were randomized, excluding who attempted to be randomized more than once into a bococizumab CV outcomes trial (B1481022/B1481038) or attempted to be randomized in more than 1 CV outcomes trial and all participants enrolled at study Site 3027 where a quality-related event was identified.
Arm/Group Title Placebo Bococizumab (PF-04950615)
Hide Arm/Group Description:
Participants received single dose of placebo matched to PF-04950615 subcutaneous injection once in every 2 weeks over a period of 3 years. Participants were followed up to 40 days after the last dose.
Participants received single dose of PF-04950615, 150 milligrams, subcutaneous injection once in every 2 weeks over a period of 3 years. Participants were followed up to 40 days after the last dose.
Overall Number of Participants Analyzed 5283 5281
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Events per 100 participant-years
3.73
(3.23 to 4.28)
2.70
(2.27 to 3.17)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Bococizumab (PF-04950615)
Comments Hazard ratio and 95% CI were obtained from a Cox proportional hazards model stratified by geographic region and complete statin intolerance with treatment as a covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.002981
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.72
Confidence Interval (2-Sided) 95%
0.58 to 0.90
Estimation Comments [Not Specified]
20.Secondary Outcome
Title Event Rate Per 100 Participant-years for First Occurrence of Any Arterial Revascularizations
Hide Description Event rate per 100 participant-years for first occurrence of any arterial revascularizations (adjudicated by Adjudication Committee) was reported. Event rate was calculated as the number of events per 100 participant-years at risk.
Time Frame From baseline until the date of first adjudicated and confirmed occurrence of any arterial revascularizations (maximum duration: up to 3.4 years)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS: all participants who were randomized, excluding who attempted to be randomized more than once into a bococizumab CV outcomes trial (B1481022/B1481038) or attempted to be randomized in more than 1 CV outcomes trial and all participants enrolled at study Site 3027 where a quality-related event was identified.
Arm/Group Title Placebo Bococizumab (PF-04950615)
Hide Arm/Group Description:
Participants received single dose of placebo matched to PF-04950615 subcutaneous injection once in every 2 weeks over a period of 3 years. Participants were followed up to 40 days after the last dose.
Participants received single dose of PF-04950615, 150 milligrams, subcutaneous injection once in every 2 weeks over a period of 3 years. Participants were followed up to 40 days after the last dose.
Overall Number of Participants Analyzed 5283 5281
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Events per 100 participant-years
1.51
(1.20 to 1.88)
1.44
(1.14 to 1.80)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Bococizumab (PF-04950615)
Comments Hazard ratio and 95% CI were obtained from a Cox proportional hazards model stratified by geographic region and complete statin intolerance with treatment as a covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.748975
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.95
Confidence Interval (2-Sided) 95%
0.70 to 1.30
Estimation Comments [Not Specified]
21.Secondary Outcome
Title Event Rate Per 100 Participant-years for All-cause Death
Hide Description Event rate per 100 participant-years for occurrence of all-cause death (adjudicated by Adjudication Committee) was reported. All-cause death was defined as the death due to any cause during the course of study. Event rate was calculated as the number of events per 100 participant-years at risk.
Time Frame From baseline until the date of adjudicated and confirmed occurrence of all-cause death (maximum duration: up to 3.4 years)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS: all participants who were randomized, excluding who attempted to be randomized more than once into a bococizumab CV outcomes trial (B1481022/B1481038) or attempted to be randomized in more than 1 CV outcomes trial and all participants enrolled at study Site 3027 where a quality-related event was identified.
Arm/Group Title Placebo Bococizumab (PF-04950615)
Hide Arm/Group Description:
Participants received single dose of placebo matched to PF-04950615 subcutaneous injection once in every 2 weeks over a period of 3 years. Participants were followed up to 40 days after the last dose.
Participants received single dose of PF-04950615, 150 milligrams, subcutaneous injection once in every 2 weeks over a period of 3 years. Participants were followed up to 40 days after the last dose.
Overall Number of Participants Analyzed 5283 5281
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Events per 100 participant-years
1.06
(0.81 to 1.37)
0.97
(0.73 to 1.27)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Bococizumab (PF-04950615)
Comments Hazard ratio and 95% CI were obtained from a Cox proportional hazards model stratified by geographic region and complete statin intolerance with treatment as a covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.626157
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.91
Confidence Interval (2-Sided) 95%
0.63 to 1.32
Estimation Comments [Not Specified]
22.Secondary Outcome
Title Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) at Week 14
Hide Description [Not Specified]
Time Frame Baseline, Week 14
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on FAS. Here, "Number of participants analyzed" (N) signifies those participants who were evaluable for this outcome measure.
Arm/Group Title Placebo Bococizumab (PF-04950615)
Hide Arm/Group Description:
Participants received single dose of placebo matched to PF-04950615 subcutaneous injection once in every 2 weeks over a period of 3 years. Participants were followed up to 40 days after the last dose.
Participants received single dose of PF-04950615, 150 milligrams, subcutaneous injection once in every 2 weeks over a period of 3 years. Participants were followed up to 40 days after the last dose.
Overall Number of Participants Analyzed 4712 4654
Least Squares Mean (Standard Error)
Unit of Measure: Percent change
2.13  (0.36) -54.77  (0.36)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Bococizumab (PF-04950615)
Comments Least square (LS) mean differences, associated 95% CI, and p-values were from an mixed model repeated measures (MMRM) model including observations through Week 70 with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction, geographic region and complete statin intolerance.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -56.90
Confidence Interval (2-Sided) 95%
-57.91 to -55.89
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.51
Estimation Comments [Not Specified]
23.Secondary Outcome
Title Nominal Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) at Week 14
Hide Description [Not Specified]
Time Frame Baseline, Week 14
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on FAS. Here, "N" signifies those participants who were evaluable for this outcome measure.
Arm/Group Title Placebo Bococizumab (PF-04950615)
Hide Arm/Group Description:
Participants received single dose of placebo matched to PF-04950615 subcutaneous injection once in every 2 weeks over a period of 3 years. Participants were followed up to 40 days after the last dose.
Participants received single dose of PF-04950615, 150 milligrams, subcutaneous injection once in every 2 weeks over a period of 3 years. Participants were followed up to 40 days after the last dose.
Overall Number of Participants Analyzed 4712 4654
Least Squares Mean (Standard Error)
Unit of Measure: mg/dL
0.69  (0.47) -73.11  (0.47)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Bococizumab (PF-04950615)
Comments LS mean differences, associated 95% CI, and p-values were from an MMRM model including observations through Week 70 with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction, geographic region and complete statin intolerance.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -73.80
Confidence Interval (2-Sided) 95%
-75.11 to -72.50
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.67
Estimation Comments [Not Specified]
24.Secondary Outcome
Title Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) at Last Post-baseline Measurement
Hide Description [Not Specified]
Time Frame Baseline, last post-baseline measurement (any time up to Week 140)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on FAS. Here, "N" signifies those participants who were evaluable for this outcome measure.
Arm/Group Title Placebo Bococizumab (PF-04950615)
Hide Arm/Group Description:
Participants received single dose of placebo matched to PF-04950615 subcutaneous injection once in every 2 weeks over a period of 3 years. Participants were followed up to 40 days after the last dose.
Participants received single dose of PF-04950615, 150 milligrams, subcutaneous injection once in every 2 weeks over a period of 3 years. Participants were followed up to 40 days after the last dose.
Overall Number of Participants Analyzed 5242 5246
Least Squares Mean (Standard Error)
Unit of Measure: Percent change
2.90  (0.45) -36.41  (0.45)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Bococizumab (PF-04950615)
Comments LS-mean difference, associated 95% CI, and p-value were from an analysis of covariance (ANCOVA) model with fixed effects for treatment group, baseline value, geographic region and complete statin intolerance.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -39.31
Confidence Interval (2-Sided) 95%
-40.55 to -38.06
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.64
Estimation Comments [Not Specified]
25.Secondary Outcome
Title Percent Change From Baseline in Lipid Levels at Week 14
Hide Description Lipids included non-high density lipoprotein cholesterol (non-HDL-C), very low density lipoprotein cholesterol (VLDL-C), remnant lipoprotein cholesterol (RLP-C), apolipoprotein B (Apo B), HDL-C, apolipoprotein A-I (Apo A-I) and total cholesterol.
Time Frame Baseline, Week 14
Hide Outcome Measure Data
Hide Analysis Population Description
FAS population. Here, number analyzed "n" signifies number of participants who were evaluable for the specified categories.
Arm/Group Title Placebo Bococizumab (PF-04950615)
Hide Arm/Group Description:
Participants received single dose of placebo matched to PF-04950615 subcutaneous injection once in every 2 weeks over a period of 3 years. Participants were followed up to 40 days after the last dose.
Participants received single dose of PF-04950615, 150 milligrams, subcutaneous injection once in every 2 weeks over a period of 3 years. Participants were followed up to 40 days after the last dose.
Overall Number of Participants Analyzed 5283 5281
Least Squares Mean (Standard Error)
Unit of Measure: Percent change
Non-HDL-C Number Analyzed 4698 participants 4646 participants
1.82  (0.34) -50.05  (0.34)
VLDL-C Number Analyzed 4711 participants 4657 participants
4.88  (0.56) -13.54  (0.56)
RLP-C Number Analyzed 4696 participants 4635 participants
8.76  (0.81) -20.44  (0.81)
Apo B Number Analyzed 4616 participants 4588 participants
1.89  (0.35) -49.51  (0.35)
HDL-C Number Analyzed 4698 participants 4647 participants
1.05  (0.21) 7.96  (0.21)
Apo A-I Number Analyzed 4617 participants 4588 participants
0.07  (0.18) 4.46  (0.18)
Total cholesterol Number Analyzed 4711 participants 4658 participants
1.26  (0.28) -36.72  (0.28)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Bococizumab (PF-04950615)
Comments Non-HDLC: LS-mean differences, associated 95% CI, and p-values were from an MMRM model including observations through Week 70 with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction, geographic region and complete statin intolerance.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -51.87
Confidence Interval (2-Sided) 95%
-52.81 to -50.94
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.48
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Bococizumab (PF-04950615)
Comments VLDL-C: LS-mean differences, associated 95% CI, and p-values were from an MMRM model including observations through Week 70 with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction, geographic region and complete statin intolerance.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -18.41
Confidence Interval (2-Sided) 95%
-19.96 to -16.86
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.79
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Bococizumab (PF-04950615)
Comments RLP-C: LS-mean differences, associated 95% CI, and p-values were from an MMRM model including observations through Week 70 with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction, geographic region and complete statin intolerance.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -29.20
Confidence Interval (2-Sided) 95%
-31.44 to -26.96
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.14
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Bococizumab (PF-04950615)
Comments Apo B: LS-mean differences, associated 95% CI, and p-values were from an MMRM model including observations through Week 52 with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction, geographic region and complete statin intolerance.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -51.40
Confidence Interval (2-Sided) 95%
-52.37 to -50.42
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.50
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, Bococizumab (PF-04950615)
Comments HDL-C: LS-mean differences, associated 95% CI, and p-values were from an MMRM model including observations through Week 70 with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction, geographic region and complete statin intolerance.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 6.91
Confidence Interval (2-Sided) 95%
6.33 to 7.50
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.30
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, Bococizumab (PF-04950615)
Comments Apo A-I: LS-mean differences, associated 95% CI, and p-values were from an MMRM model including observations through Week 52 with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction, geographic region and complete statin intolerance.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 4.40
Confidence Interval (2-Sided) 95%
3.90 to 4.90
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.25
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Placebo, Bococizumab (PF-04950615)
Comments Total cholesterol: LS-mean differences, associated 95% CI, and p-values were from an MMRM model including observations through Week 70 with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction, geographic region and complete statin intolerance.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -37.99
Confidence Interval (2-Sided) 95%
-38.75 to -37.22
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.39
Estimation Comments [Not Specified]
26.Secondary Outcome
Title Percent Change From Baseline in Log-transformed Triglycerides and Lipoprotein (a) (Lp[a]) at Week 14
Hide Description [Not Specified]
Time Frame Baseline, Week 14
Hide Outcome Measure Data
Hide Analysis Population Description
FAS population. Here, number analyzed "n" signifies number of participants who were evaluable for the specified categories.
Arm/Group Title Placebo Bococizumab (PF-04950615)
Hide Arm/Group Description:
Participants received single dose of placebo matched to PF-04950615 subcutaneous injection once in every 2 weeks over a period of 3 years. Participants were followed up to 40 days after the last dose.
Participants received single dose of PF-04950615, 150 milligrams, subcutaneous injection once in every 2 weeks over a period of 3 years. Participants were followed up to 40 days after the last dose.
Overall Number of Participants Analyzed 5283 5281
Mean (Standard Deviation)
Unit of Measure: Percent change
Triglycerides Number Analyzed 4711 participants 4657 participants
-1.4  (34.55) -19.7  (30.71)
Lp(a) Number Analyzed 4650 participants 4598 participants
-2.0  (31.03) -33.3  (31.21)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Bococizumab (PF-04950615)
Comments Triglycerides: LS-mean differences, associated 95% CI and p-values were from an MMRM model including observations through Week 70 on the difference of log-transformed observations with fixed effects for treatment group, visit, treatment group*visit interaction, log-transformed baseline value, log-transformed baseline value*visit interaction, geographical region and complete statin intolerance. The 95% CI was derived by exponentiating the LS-mean difference confidence interval from the log scale.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 0.82
Confidence Interval (2-Sided) 95%
0.81 to 0.83
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Bococizumab (PF-04950615)
Comments Lp(a): LS-mean differences, associated 95% CI and p-values were from an MMRM model on the Difference of log-transformed observations with fixed effects for treatment group, visit, a treatment group*visit interaction, log-transformed baseline value, log-transformed baseline value*visit interaction, geographical region and complete statin intolerance. The 95% CI was derived by exponentiating the LS-mean difference confidence interval from the log scale.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 0.68
Confidence Interval (2-Sided) 95%
0.67 to 0.69
Estimation Comments [Not Specified]
27.Secondary Outcome
Title Percent Change From Baseline in Log-transformed High Sensitivity C-Reactive Protein (Hs-CRP) at Week 14
Hide Description [Not Specified]
Time Frame Baseline, Week 14
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on FAS. Here, "N" signifies those participants who were evaluable for this outcome measure.
Arm/Group Title Placebo Bococizumab (PF-04950615)
Hide Arm/Group Description:
Participants received single dose of placebo matched to PF-04950615 subcutaneous injection once in every 2 weeks over a period of 3 years. Participants were followed up to 40 days after the last dose.
Participants received single dose of PF-04950615, 150 milligrams, subcutaneous injection once in every 2 weeks over a period of 3 years. Participants were followed up to 40 days after the last dose.
Overall Number of Participants Analyzed 4655 4620
Mean (Standard Deviation)
Unit of Measure: Percent change
-4.8  (83.68) 0.3  (90.03)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Bococizumab (PF-04950615)
Comments LS-mean differences, associated 95% CI and p-values were from an MMRM model on the difference of log-transformed observations with fixed effects for treatment group, visit, treatment group*visit interaction, log-transformed baseline value, log-transformed baseline value*visit interaction, geographical region and complete statin intolerance.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.002
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 1.06
Confidence Interval (2-Sided) 95%
1.02 to 1.09
Estimation Comments [Not Specified]
Time Frame Baseline up to 3.4 years
Adverse Event Reporting Description Safety analysis set: all participants who randomized, had atleast 1 dose of study drug, excluding those attempted to randomize more than once in a bococizumab CV outcomes trial (B1481022/B1481038) or attempted to randomize in more than 1 CV outcomes trial, and all participants enrolled at study Site 3027 where a quality-related event was identified
 
Arm/Group Title Placebo Bococizumab (PF-04950615)
Hide Arm/Group Description Participants received single dose of placebo matched to PF-04950615 subcutaneous injection once in every 2 weeks over a period of 3 years. Participants were followed up to 40 days after the last dose. Participants received single dose of PF-04950615, 150 milligrams, subcutaneous injection once in every 2 weeks over a period of 3 years. Participants were followed up to 40 days after the last dose.
All-Cause Mortality
Placebo Bococizumab (PF-04950615)
Affected / at Risk (%) Affected / at Risk (%)
Total   61/5279 (1.16%)   54/5276 (1.02%) 
Show Serious Adverse Events Hide Serious Adverse Events
Placebo Bococizumab (PF-04950615)
Affected / at Risk (%) Affected / at Risk (%)
Total   994/5279 (18.83%)   934/5276 (17.70%) 
Blood and lymphatic system disorders     
Anaemia * 1  4/5279 (0.08%)  6/5276 (0.11%) 
Autoimmune haemolytic anaemia * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Haemorrhagic anaemia * 1  2/5279 (0.04%)  3/5276 (0.06%) 
Hypochromic anaemia * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Iron deficiency anaemia * 1  1/5279 (0.02%)  1/5276 (0.02%) 
Leukocytosis * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Pancytopenia * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Cardiac disorders     
Acute coronary syndrome * 1  7/5279 (0.13%)  9/5276 (0.17%) 
Acute left ventricular failure * 1  2/5279 (0.04%)  0/5276 (0.00%) 
Acute myocardial infarction * 1  40/5279 (0.76%)  30/5276 (0.57%) 
Angina pectoris * 1  92/5279 (1.74%)  64/5276 (1.21%) 
Angina unstable * 1  93/5279 (1.76%)  73/5276 (1.38%) 
Anginal equivalent * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Aortic valve incompetence * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Aortic valve stenosis * 1  3/5279 (0.06%)  3/5276 (0.06%) 
Arrhythmia * 1  3/5279 (0.06%)  4/5276 (0.08%) 
Arrhythmia supraventricular * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Arteriosclerosis coronary artery * 1  3/5279 (0.06%)  3/5276 (0.06%) 
Arteriospasm coronary * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Atrial fibrillation * 1  34/5279 (0.64%)  26/5276 (0.49%) 
Atrial flutter * 1  9/5279 (0.17%)  5/5276 (0.09%) 
Atrial thrombosis * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Atrioventricular block * 1  3/5279 (0.06%)  4/5276 (0.08%) 
Atrioventricular block complete * 1  1/5279 (0.02%)  4/5276 (0.08%) 
Atrioventricular block second degree * 1  3/5279 (0.06%)  1/5276 (0.02%) 
Bradycardia * 1  7/5279 (0.13%)  1/5276 (0.02%) 
Cardiac arrest * 1  5/5279 (0.09%)  4/5276 (0.08%) 
Cardiac failure * 1  15/5279 (0.28%)  16/5276 (0.30%) 
Cardiac failure acute * 1  0/5279 (0.00%)  3/5276 (0.06%) 
Cardiac failure chronic * 1  3/5279 (0.06%)  2/5276 (0.04%) 
Cardiac failure congestive * 1  31/5279 (0.59%)  24/5276 (0.45%) 
Cardiac valve disease * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Cardio-respiratory arrest * 1  2/5279 (0.04%)  0/5276 (0.00%) 
Cardiogenic shock * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Cardiomyopathy * 1  1/5279 (0.02%)  1/5276 (0.02%) 
Cardiopulmonary failure * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Cardiorenal syndrome * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Conduction disorder * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Congestive cardiomyopathy * 1  2/5279 (0.04%)  1/5276 (0.02%) 
Coronary artery disease * 1  31/5279 (0.59%)  29/5276 (0.55%) 
Coronary artery insufficiency * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Coronary artery occlusion * 1  5/5279 (0.09%)  5/5276 (0.09%) 
Coronary artery stenosis * 1  17/5279 (0.32%)  7/5276 (0.13%) 
Coronary artery thrombosis * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Diastolic dysfunction * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Dressler's syndrome * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Ischaemic cardiomyopathy * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Left ventricular dysfunction * 1  2/5279 (0.04%)  0/5276 (0.00%) 
Left ventricular failure * 1  3/5279 (0.06%)  1/5276 (0.02%) 
Left ventricular hypertrophy * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Mitral valve incompetence * 1  2/5279 (0.04%)  0/5276 (0.00%) 
Myocardial infarction * 1  52/5279 (0.99%)  34/5276 (0.64%) 
Myocardial ischaemia * 1  10/5279 (0.19%)  9/5276 (0.17%) 
Palpitations * 1  2/5279 (0.04%)  1/5276 (0.02%) 
Pericarditis * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Sinus arrhythmia * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Sinus node dysfunction * 1  4/5279 (0.08%)  4/5276 (0.08%) 
Sinus tachycardia * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Supraventricular tachycardia * 1  2/5279 (0.04%)  3/5276 (0.06%) 
Systolic dysfunction * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Tachycardia * 1  2/5279 (0.04%)  0/5276 (0.00%) 
Tachycardia paroxysmal * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Torsade de pointes * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Trifascicular block * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Ventricular arrhythmia * 1  1/5279 (0.02%)  1/5276 (0.02%) 
Ventricular extrasystoles * 1  3/5279 (0.06%)  6/5276 (0.11%) 
Ventricular fibrillation * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Ventricular tachycardia * 1  5/5279 (0.09%)  5/5276 (0.09%) 
Congenital, familial and genetic disorders     
Hydrocele * 1 [1]  0/3434 (0.00%)  1/3489 (0.03%) 
Phimosis * 1 [1]  1/3434 (0.03%)  0/3489 (0.00%) 
Ear and labyrinth disorders     
Sudden hearing loss * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Tinnitus * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Vertigo * 1  2/5279 (0.04%)  3/5276 (0.06%) 
Vertigo positional * 1  1/5279 (0.02%)  1/5276 (0.02%) 
Vestibular disorder * 1  1/5279 (0.02%)  1/5276 (0.02%) 
Endocrine disorders     
Addison's disease * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Goitre * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Hyperparathyroidism * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Hyperthyroidism * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Hypothyroidism * 1  0/5279 (0.00%)  2/5276 (0.04%) 
Thyroid mass * 1  0/5279 (0.00%)  2/5276 (0.04%) 
Eye disorders     
Amaurosis fugax * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Cataract * 1  1/5279 (0.02%)  2/5276 (0.04%) 
Diabetic retinopathy * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Diplopia * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Macular fibrosis * 1  1/5279 (0.02%)  1/5276 (0.02%) 
Retinal detachment * 1  1/5279 (0.02%)  1/5276 (0.02%) 
Retinal haemorrhage * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Retinal infarction * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Vitreous haemorrhage * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Gastrointestinal disorders     
Abdominal adhesions * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Abdominal hernia * 1  0/5279 (0.00%)  3/5276 (0.06%) 
Abdominal pain * 1  5/5279 (0.09%)  3/5276 (0.06%) 
Abdominal pain upper * 1  3/5279 (0.06%)  4/5276 (0.08%) 
Acute abdomen * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Anal fistula * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Anal incontinence * 1  1/5279 (0.02%)  1/5276 (0.02%) 
Coeliac artery stenosis * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Colitis * 1  1/5279 (0.02%)  2/5276 (0.04%) 
Colitis ischaemic * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Constipation * 1  0/5279 (0.00%)  2/5276 (0.04%) 
Crohn's disease * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Diarrhoea * 1  3/5279 (0.06%)  2/5276 (0.04%) 
Diverticular perforation * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Diverticulum * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Diverticulum intestinal * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Diverticulum oesophageal * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Duodenal ulcer * 1  1/5279 (0.02%)  1/5276 (0.02%) 
Dyspepsia * 1  2/5279 (0.04%)  0/5276 (0.00%) 
Dysphagia * 1  1/5279 (0.02%)  1/5276 (0.02%) 
Enteritis * 1  1/5279 (0.02%)  1/5276 (0.02%) 
Erosive oesophagitis * 1  0/5279 (0.00%)  2/5276 (0.04%) 
Faecaloma * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Gastric disorder * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Gastric haemorrhage * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Gastric ulcer * 1  1/5279 (0.02%)  3/5276 (0.06%) 
Gastric ulcer haemorrhage * 1  1/5279 (0.02%)  1/5276 (0.02%) 
Gastritis * 1  5/5279 (0.09%)  5/5276 (0.09%) 
Gastritis haemorrhagic * 1  0/5279 (0.00%)  2/5276 (0.04%) 
Gastrointestinal haemorrhage * 1  4/5279 (0.08%)  6/5276 (0.11%) 
Gastrooesophageal reflux disease * 1  3/5279 (0.06%)  1/5276 (0.02%) 
Haematochezia * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Haemorrhagic erosive gastritis * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Ileus * 1  1/5279 (0.02%)  1/5276 (0.02%) 
Ileus paralytic * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Impaired gastric emptying * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Incarcerated umbilical hernia * 1 [1]  1/1849 (0.05%)  0/1792 (0.00%) 
Inguinal hernia * 1  2/5279 (0.04%)  4/5276 (0.08%) 
Intestinal haemorrhage * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Intestinal ischaemia * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Intestinal obstruction * 1  1/5279 (0.02%)  2/5276 (0.04%) 
Intestinal perforation * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Irritable bowel syndrome * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Large intestinal obstruction * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Large intestine polyp * 1  1/5279 (0.02%)  1/5276 (0.02%) 
Lip disorder * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Lower gastrointestinal haemorrhage * 1  0/5279 (0.00%)  4/5276 (0.08%) 
Mallory-Weiss syndrome * 1  1/5279 (0.02%)  1/5276 (0.02%) 
Nausea * 1  3/5279 (0.06%)  1/5276 (0.02%) 
Oesophageal food impaction * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Oesophageal spasm * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Pancreatitis * 1  4/5279 (0.08%)  6/5276 (0.11%) 
Pancreatitis acute * 1  4/5279 (0.08%)  3/5276 (0.06%) 
Pancreatitis chronic * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Reactive gastropathy * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Rectal haemorrhage * 1  3/5279 (0.06%)  3/5276 (0.06%) 
Rectal polyp * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Retroperitoneal haematoma * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Small intestinal obstruction * 1  2/5279 (0.04%)  5/5276 (0.09%) 
Strangulated umbilical hernia * 1 [1]  0/1849 (0.00%)  1/1792 (0.06%) 
Ulcerative gastritis * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Umbilical hernia * 1 [1]  2/1849 (0.11%)  1/1792 (0.06%) 
Umbilical hernia, obstructive * 1 [1]  0/1849 (0.00%)  1/1792 (0.06%) 
Upper gastrointestinal haemorrhage * 1  0/5279 (0.00%)  2/5276 (0.04%) 
Vomiting * 1  2/5279 (0.04%)  4/5276 (0.08%) 
General disorders     
Adverse drug reaction * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Asthenia * 1  3/5279 (0.06%)  1/5276 (0.02%) 
Cardiac death * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Chest discomfort * 1  3/5279 (0.06%)  1/5276 (0.02%) 
Chest pain * 1  14/5279 (0.27%)  8/5276 (0.15%) 
Complication associated with device * 1  1/5279 (0.02%)  1/5276 (0.02%) 
Death * 1  6/5279 (0.11%)  9/5276 (0.17%) 
Drug withdrawal syndrome * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Fatigue * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Hernia * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Ill-defined disorder * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Impaired healing * 1  1/5279 (0.02%)  1/5276 (0.02%) 
Inflammation * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Multi-organ disorder * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Multiple organ dysfunction syndrome * 1  1/5279 (0.02%)  2/5276 (0.04%) 
Non-cardiac chest pain * 1  50/5279 (0.95%)  32/5276 (0.61%) 
Oedema peripheral * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Pain * 1  2/5279 (0.04%)  0/5276 (0.00%) 
Peripheral swelling * 1  2/5279 (0.04%)  0/5276 (0.00%) 
Polyp * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Pyrexia * 1  3/5279 (0.06%)  1/5276 (0.02%) 
Stenosis * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Sudden cardiac death * 1  8/5279 (0.15%)  5/5276 (0.09%) 
Sudden death * 1  3/5279 (0.06%)  2/5276 (0.04%) 
Systemic inflammatory response syndrome * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Vascular stent restenosis * 1  2/5279 (0.04%)  1/5276 (0.02%) 
Vascular stent stenosis * 1  1/5279 (0.02%)  2/5276 (0.04%) 
Vascular stent thrombosis * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Hepatobiliary disorders     
Alcoholic liver disease * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Bile duct obstruction * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Bile duct stone * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Biliary colic * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Biliary fistula * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Cholangitis * 1  1/5279 (0.02%)  1/5276 (0.02%) 
Cholecystitis * 1  6/5279 (0.11%)  5/5276 (0.09%) 
Cholecystitis acute * 1  4/5279 (0.08%)  4/5276 (0.08%) 
Cholecystitis chronic * 1  2/5279 (0.04%)  0/5276 (0.00%) 
Cholelithiasis * 1  7/5279 (0.13%)  5/5276 (0.09%) 
Drug-induced liver injury * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Gallbladder perforation * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Gallbladder polyp * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Jaundice * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Liver injury * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Immune system disorders     
Anaphylactic reaction * 1  1/5279 (0.02%)  2/5276 (0.04%) 
Drug hypersensitivity * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Food allergy * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Hypersensitivity * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Immunosuppression * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Infections and infestations     
Abdominal wall abscess * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Abscess * 1  1/5279 (0.02%)  1/5276 (0.02%) 
Abscess intestinal * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Abscess limb * 1  1/5279 (0.02%)  2/5276 (0.04%) 
Anal abscess * 1  0/5279 (0.00%)  4/5276 (0.08%) 
Appendicitis * 1  5/5279 (0.09%)  4/5276 (0.08%) 
Arteriovenous graft site infection * 1  2/5279 (0.04%)  0/5276 (0.00%) 
Arthritis infective * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Bacteraemia * 1  2/5279 (0.04%)  0/5276 (0.00%) 
Bacterial diarrhoea * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Biliary sepsis * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Bronchitis * 1  7/5279 (0.13%)  5/5276 (0.09%) 
Campylobacter gastroenteritis * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Cardiac valve vegetation * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Cellulitis * 1  10/5279 (0.19%)  8/5276 (0.15%) 
Cholecystitis infective * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Chronic sinusitis * 1  2/5279 (0.04%)  0/5276 (0.00%) 
Clostridium difficile colitis * 1  3/5279 (0.06%)  2/5276 (0.04%) 
Clostridium difficile infection * 1  2/5279 (0.04%)  1/5276 (0.02%) 
Cystitis * 1  0/5279 (0.00%)  2/5276 (0.04%) 
Device related infection * 1  0/5279 (0.00%)  2/5276 (0.04%) 
Diabetic foot infection * 1  2/5279 (0.04%)  2/5276 (0.04%) 
Diabetic gangrene * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Diverticulitis * 1  5/5279 (0.09%)  6/5276 (0.11%) 
Endocarditis * 1  2/5279 (0.04%)  2/5276 (0.04%) 
Epididymitis * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Epstein-Barr virus infection * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Erysipelas * 1  2/5279 (0.04%)  2/5276 (0.04%) 
Escherichia bacteraemia * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Gangrene * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Gastritis viral * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Gastroenteritis * 1  6/5279 (0.11%)  2/5276 (0.04%) 
Gastroenteritis clostridial * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Gastroenteritis viral * 1  3/5279 (0.06%)  3/5276 (0.06%) 
Groin abscess * 1  1/5279 (0.02%)  1/5276 (0.02%) 
Groin infection * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Haematoma infection * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Hepatic cyst infection * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Hepatitis A * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Hepatitis C * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Herpes zoster * 1  2/5279 (0.04%)  0/5276 (0.00%) 
Incision site infection * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Infected skin ulcer * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Infection * 1  0/5279 (0.00%)  3/5276 (0.06%) 
Infectious colitis * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Infectious pleural effusion * 1  1/5279 (0.02%)  1/5276 (0.02%) 
Influenza * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Kidney infection * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Laryngitis * 1  1/5279 (0.02%)  1/5276 (0.02%) 
Localised infection * 1  1/5279 (0.02%)  4/5276 (0.08%) 
Lower respiratory tract infection * 1  4/5279 (0.08%)  1/5276 (0.02%) 
Lung abscess * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Medical device site abscess * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Muscle abscess * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Necrotising fasciitis * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Osteomyelitis * 1  3/5279 (0.06%)  4/5276 (0.08%) 
Otitis externa * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Pelvic abscess * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Peritonitis * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Pneumonia * 1  35/5279 (0.66%)  28/5276 (0.53%) 
Pneumonia bacterial * 1  0/5279 (0.00%)  2/5276 (0.04%) 
Pneumonia influenzal * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Pneumonia legionella * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Post procedural pneumonia * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Postoperative wound infection * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Pulmonary sepsis * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Pyelocystitis * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Pyelonephritis * 1  1/5279 (0.02%)  5/5276 (0.09%) 
Pyelonephritis acute * 1  0/5279 (0.00%)  2/5276 (0.04%) 
Rectal abscess * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Respiratory tract infection * 1  1/5279 (0.02%)  2/5276 (0.04%) 
Scrotal abscess * 1  1/5279 (0.02%)  1/5276 (0.02%) 
Sebaceous gland infection * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Sepsis * 1  5/5279 (0.09%)  13/5276 (0.25%) 
Septic shock * 1  3/5279 (0.06%)  2/5276 (0.04%) 
Sinusitis * 1  1/5279 (0.02%)  2/5276 (0.04%) 
Sinusitis bacterial * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Staphylococcal bacteraemia * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Staphylococcal infection * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Staphylococcal sepsis * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Subcutaneous abscess * 1  1/5279 (0.02%)  1/5276 (0.02%) 
Tick-borne viral encephalitis * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Tooth abscess * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Tracheobronchitis * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Upper respiratory tract infection * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Urinary tract infection * 1  15/5279 (0.28%)  9/5276 (0.17%) 
Urosepsis * 1  1/5279 (0.02%)  3/5276 (0.06%) 
Viral infection * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Viral sepsis * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Wound infection * 1  2/5279 (0.04%)  2/5276 (0.04%) 
Injury, poisoning and procedural complications     
Acoustic shock * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Ankle fracture * 1  2/5279 (0.04%)  1/5276 (0.02%) 
Arterial bypass thrombosis * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Arterial restenosis * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Arthropod sting * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Cardiac procedure complication * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Clavicle fracture * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Concussion * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Contusion * 1  3/5279 (0.06%)  0/5276 (0.00%) 
Craniocerebral injury * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Dural tear * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Fall * 1  6/5279 (0.11%)  7/5276 (0.13%) 
Femoral neck fracture * 1  3/5279 (0.06%)  5/5276 (0.09%) 
Femur fracture * 1  5/5279 (0.09%)  3/5276 (0.06%) 
Fibula fracture * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Foot fracture * 1  3/5279 (0.06%)  2/5276 (0.04%) 
Fractured sacrum * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Gallbladder injury * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Gastrointestinal stoma complication * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Hand fracture * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Hip fracture * 1  2/5279 (0.04%)  2/5276 (0.04%) 
Humerus fracture * 1  2/5279 (0.04%)  0/5276 (0.00%) 
Incarcerated incisional hernia * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Incisional hernia * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Injury * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Intentional overdose * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Joint dislocation * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Kidney rupture * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Ligament injury * 1  0/5279 (0.00%)  2/5276 (0.04%) 
Ligament rupture * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Limb injury * 1  4/5279 (0.08%)  2/5276 (0.04%) 
Lower limb fracture * 1  2/5279 (0.04%)  2/5276 (0.04%) 
Lumbar vertebral fracture * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Meniscus injury * 1  1/5279 (0.02%)  1/5276 (0.02%) 
Muscle rupture * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Neck injury * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Overdose * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Patella fracture * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Pelvic fracture * 1  1/5279 (0.02%)  1/5276 (0.02%) 
Peripheral artery restenosis * 1  1/5279 (0.02%)  1/5276 (0.02%) 
Post procedural complication * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Post procedural haemorrhage * 1  1/5279 (0.02%)  2/5276 (0.04%) 
Postoperative fever * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Postoperative ileus * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Postoperative respiratory failure * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Postoperative wound complication * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Procedural haemorrhage * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Procedural pain * 1  2/5279 (0.04%)  1/5276 (0.02%) 
Radius fracture * 1  1/5279 (0.02%)  1/5276 (0.02%) 
Rib fracture * 1  1/5279 (0.02%)  1/5276 (0.02%) 
Road traffic accident * 1  2/5279 (0.04%)  2/5276 (0.04%) 
Skull fracture * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Spinal compression fracture * 1  0/5279 (0.00%)  2/5276 (0.04%) 
Subarachnoid haemorrhage * 1  0/5279 (0.00%)  2/5276 (0.04%) 
Subdural haematoma * 1  1/5279 (0.02%)  1/5276 (0.02%) 
Subdural haemorrhage * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Suture related complication * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Tendon rupture * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Tibia fracture * 1  1/5279 (0.02%)  2/5276 (0.04%) 
Traumatic liver injury * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Traumatic renal injury * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Upper limb fracture * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Urinary tract stoma complication * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Vascular graft occlusion * 1  2/5279 (0.04%)  0/5276 (0.00%) 
Vascular procedure complication * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Vascular pseudoaneurysm * 1  2/5279 (0.04%)  2/5276 (0.04%) 
Wound * 1  2/5279 (0.04%)  2/5276 (0.04%) 
Wound dehiscence * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Wound necrosis * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Investigations     
Alanine aminotransferase increased * 1  2/5279 (0.04%)  1/5276 (0.02%) 
Anticoagulation drug level above therapeutic * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Aspartate aminotransferase increased * 1  2/5279 (0.04%)  1/5276 (0.02%) 
Blood creatine phosphokinase increased * 1  2/5279 (0.04%)  1/5276 (0.02%) 
Blood glucose increased * 1  2/5279 (0.04%)  1/5276 (0.02%) 
Blood ketone body increased * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Blood magnesium decreased * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Blood pressure increased * 1  1/5279 (0.02%)  0/5276 (0.00%) 
ECG signs of myocardial ischaemia * 1  2/5279 (0.04%)  0/5276 (0.00%) 
Ejection fraction abnormal * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Electrocardiogram ST segment elevation * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Electrocardiogram T wave inversion * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Exercise test abnormal * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Gamma-glutamyltransferase increased * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Hepatic enzyme increased * 1  2/5279 (0.04%)  2/5276 (0.04%) 
Liver function test abnormal * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Liver function test increased * 1  2/5279 (0.04%)  1/5276 (0.02%) 
Myocardial necrosis marker increased * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Neurological examination * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Prostatic specific antigen increased * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Renal function test abnormal * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Staphylococcus test positive * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Stress echocardiogram abnormal * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Transaminases increased * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Troponin increased * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Metabolism and nutrition disorders     
Dehydration * 1  5/5279 (0.09%)  4/5276 (0.08%) 
Diabetes mellitus * 1  5/5279 (0.09%)  4/5276 (0.08%) 
Diabetes mellitus inadequate control * 1  4/5279 (0.08%)  5/5276 (0.09%) 
Diabetic ketoacidosis * 1  0/5279 (0.00%)  3/5276 (0.06%) 
Electrolyte imbalance * 1  2/5279 (0.04%)  0/5276 (0.00%) 
Failure to thrive * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Fluid overload * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Hyperglycaemia * 1  6/5279 (0.11%)  7/5276 (0.13%) 
Hyperkalaemia * 1  2/5279 (0.04%)  1/5276 (0.02%) 
Hyperosmolar hyperglycaemic state * 1  1/5279 (0.02%)  1/5276 (0.02%) 
Hypertriglyceridaemia * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Hypoglycaemia * 1  5/5279 (0.09%)  2/5276 (0.04%) 
Hypokalaemia * 1  2/5279 (0.04%)  2/5276 (0.04%) 
Hyponatraemia * 1  1/5279 (0.02%)  1/5276 (0.02%) 
Hypovolaemia * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Metabolic acidosis * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Metabolic disorder * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Obesity * 1  0/5279 (0.00%)  3/5276 (0.06%) 
Type 2 diabetes mellitus * 1  5/5279 (0.09%)  3/5276 (0.06%) 
Musculoskeletal and connective tissue disorders     
Ankylosing spondylitis * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Arthralgia * 1  2/5279 (0.04%)  1/5276 (0.02%) 
Arthritis * 1  1/5279 (0.02%)  1/5276 (0.02%) 
Back disorder * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Back pain * 1  3/5279 (0.06%)  9/5276 (0.17%) 
Bone pain * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Bursitis * 1  1/5279 (0.02%)  1/5276 (0.02%) 
Cervical spinal stenosis * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Compartment syndrome * 1  1/5279 (0.02%)  1/5276 (0.02%) 
Costochondritis * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Fibromyalgia * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Flank pain * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Haemarthrosis * 1  1/5279 (0.02%)  1/5276 (0.02%) 
Intervertebral disc degeneration * 1  1/5279 (0.02%)  1/5276 (0.02%) 
Intervertebral disc disorder * 1  2/5279 (0.04%)  1/5276 (0.02%) 
Intervertebral disc protrusion * 1  8/5279 (0.15%)  7/5276 (0.13%) 
Jaw cyst * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Lumbar spinal stenosis * 1  1/5279 (0.02%)  2/5276 (0.04%) 
Meniscal degeneration * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Muscle disorder * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Muscle spasms * 1  1/5279 (0.02%)  1/5276 (0.02%) 
Muscular weakness * 1  3/5279 (0.06%)  6/5276 (0.11%) 
Musculoskeletal chest pain * 1  2/5279 (0.04%)  0/5276 (0.00%) 
Musculoskeletal pain * 1  3/5279 (0.06%)  2/5276 (0.04%) 
Myalgia * 1  3/5279 (0.06%)  1/5276 (0.02%) 
Myopathy * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Neck pain * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Osteoarthritis * 1  16/5279 (0.30%)  17/5276 (0.32%) 
Osteochondrosis * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Osteonecrosis * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Osteonecrosis of jaw * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Osteoporosis * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Pain in extremity * 1  1/5279 (0.02%)  3/5276 (0.06%) 
Periarthritis * 1  1/5279 (0.02%)  1/5276 (0.02%) 
Peripheral arthritis * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Polyarthritis * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Polymyalgia rheumatica * 1  2/5279 (0.04%)  0/5276 (0.00%) 
Psoriatic arthropathy * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Rhabdomyolysis * 1  0/5279 (0.00%)  3/5276 (0.06%) 
Rotator cuff syndrome * 1  4/5279 (0.08%)  1/5276 (0.02%) 
Soft tissue mass * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Spinal column stenosis * 1  3/5279 (0.06%)  3/5276 (0.06%) 
Spinal disorder * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Spinal osteoarthritis * 1  1/5279 (0.02%)  3/5276 (0.06%) 
Synovial cyst * 1  2/5279 (0.04%)  0/5276 (0.00%) 
Tenosynovitis * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Tenosynovitis stenosans * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Acute myeloid leukaemia * 1  2/5279 (0.04%)  0/5276 (0.00%) 
Adenocarcinoma * 1  3/5279 (0.06%)  0/5276 (0.00%) 
Adenocarcinoma gastric * 1  2/5279 (0.04%)  0/5276 (0.00%) 
Adenocarcinoma of colon * 1  1/5279 (0.02%)  2/5276 (0.04%) 
Anal cancer * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Basal cell carcinoma * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Benign breast neoplasm * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Benign lymph node neoplasm * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Bladder neoplasm * 1  0/5279 (0.00%)  2/5276 (0.04%) 
Bladder papilloma * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Bladder transitional cell carcinoma * 1  1/5279 (0.02%)  5/5276 (0.09%) 
Bone cancer * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Bowen's disease * 1  2/5279 (0.04%)  0/5276 (0.00%) 
Brain cancer metastatic * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Brain neoplasm * 1  1/5279 (0.02%)  1/5276 (0.02%) 
Breast cancer * 1  4/5279 (0.08%)  2/5276 (0.04%) 
Breast cancer metastatic * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Breast neoplasm * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Cardiac myxoma * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Cervix carcinoma * 1 [1]  0/1849 (0.00%)  2/1792 (0.11%) 
Clear cell renal cell carcinoma * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Colon adenoma * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Colon cancer * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Colon cancer metastatic * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Colorectal cancer * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Duodenal neoplasm * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Endometrial adenocarcinoma * 1 [1]  1/1849 (0.05%)  0/1792 (0.00%) 
Follicular thyroid cancer * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Gastric adenoma * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Gastric cancer * 1  1/5279 (0.02%)  1/5276 (0.02%) 
Gastric cancer stage IV * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Gastric neoplasm * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Glioblastoma multiforme * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Hypopharyngeal cancer * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Invasive ductal breast carcinoma * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Invasive lobular breast carcinoma * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Laryngeal squamous cell carcinoma * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Lentigo maligna * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Leukaemia * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Lipoma * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Lung adenocarcinoma * 1  6/5279 (0.11%)  2/5276 (0.04%) 
Lung adenocarcinoma stage I * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Lung cancer metastatic * 1  2/5279 (0.04%)  1/5276 (0.02%) 
Lung carcinoma cell type unspecified stage IV * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Lung neoplasm * 1  1/5279 (0.02%)  1/5276 (0.02%) 
Lung neoplasm malignant * 1  6/5279 (0.11%)  3/5276 (0.06%) 
Malignant ascites * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Malignant haemangiopericytoma * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Malignant melanoma * 1  3/5279 (0.06%)  2/5276 (0.04%) 
Meningioma * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Meningioma benign * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Metastases to bone * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Metastases to central nervous system * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Metastases to liver * 1  1/5279 (0.02%)  1/5276 (0.02%) 
Metastases to lung * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Metastases to spine * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Metastasis * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Metastatic bronchial carcinoma * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Metastatic neoplasm * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Metastatic renal cell carcinoma * 1  1/5279 (0.02%)  1/5276 (0.02%) 
Neoplasm malignant * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Neoplasm skin * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Neuroendocrine carcinoma * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Non-Hodgkin's lymphoma * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Non-small cell lung cancer metastatic * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Oesophageal carcinoma * 1  1/5279 (0.02%)  1/5276 (0.02%) 
Pancreatic carcinoma * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Pancreatic neoplasm * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Papillary thyroid cancer * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Parathyroid tumour benign * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Penile squamous cell carcinoma * 1 [1]  0/3434 (0.00%)  1/3489 (0.03%) 
Prostate cancer * 1 [1]  13/3434 (0.38%)  11/3489 (0.32%) 
Rectal adenocarcinoma * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Renal cancer * 1  2/5279 (0.04%)  1/5276 (0.02%) 
Renal cell carcinoma * 1  3/5279 (0.06%)  0/5276 (0.00%) 
Renal cell carcinoma recurrent * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Renal neoplasm * 1  0/5279 (0.00%)  2/5276 (0.04%) 
Respiratory tract neoplasm * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Salivary gland neoplasm * 1  1/5279 (0.02%)  1/5276 (0.02%) 
Small cell lung cancer * 1  1/5279 (0.02%)  1/5276 (0.02%) 
Small cell lung cancer metastatic * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Squamous cell carcinoma * 1  1/5279 (0.02%)  1/5276 (0.02%) 
Thyroid cancer * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Transitional cell carcinoma * 1  1/5279 (0.02%)  1/5276 (0.02%) 
Uterine leiomyoma * 1 [1]  1/1849 (0.05%)  1/1792 (0.06%) 
Nervous system disorders     
Amputation stump pain * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Ataxia * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Balance disorder * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Basal ganglia stroke * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Brain stem haemorrhage * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Brain stem infarction * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Carotid artery disease * 1  2/5279 (0.04%)  0/5276 (0.00%) 
Carotid artery stenosis * 1  14/5279 (0.27%)  12/5276 (0.23%) 
Carpal tunnel syndrome * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Cerebellar infarction * 1  2/5279 (0.04%)  0/5276 (0.00%) 
Cerebral haemorrhage * 1  1/5279 (0.02%)  1/5276 (0.02%) 
Cerebral infarction * 1  2/5279 (0.04%)  1/5276 (0.02%) 
Cerebral ischaemia * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Cerebrovascular accident * 1  10/5279 (0.19%)  7/5276 (0.13%) 
Cervical radiculopathy * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Cervicobrachial syndrome * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Cognitive disorder * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Diabetic neuropathy * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Dizziness * 1  6/5279 (0.11%)  3/5276 (0.06%) 
Embolic cerebral infarction * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Embolic stroke * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Encephalopathy * 1  0/5279 (0.00%)  2/5276 (0.04%) 
Epilepsy * 1  1/5279 (0.02%)  1/5276 (0.02%) 
Facial paralysis * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Fahr's disease * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Haemorrhage intracranial * 1  1/5279 (0.02%)  3/5276 (0.06%) 
Haemorrhagic stroke * 1  2/5279 (0.04%)  5/5276 (0.09%) 
Headache * 1  2/5279 (0.04%)  4/5276 (0.08%) 
Hemiparesis * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Hemiplegic migraine * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Hypoaesthesia * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Hypoglycaemic coma * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Hypoxic-ischaemic encephalopathy * 1  3/5279 (0.06%)  0/5276 (0.00%) 
Intracranial aneurysm * 1  1/5279 (0.02%)  1/5276 (0.02%) 
Ischaemic cerebral infarction * 1  0/5279 (0.00%)  2/5276 (0.04%) 
Ischaemic neuropathy * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Ischaemic stroke * 1  23/5279 (0.44%)  16/5276 (0.30%) 
Lacunar infarction * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Lethargy * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Lumbar radiculopathy * 1  1/5279 (0.02%)  0/5276 (0.00%) 
Lumbosacral radiculopathy * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Memory impairment * 1  0/5279 (0.00%)  2/5276 (0.04%) 
Migraine * 1  1/5279 (0.02%)  1/5276 (0.02%) 
Monoplegia * 1  0/5279 (0.00%)  1/5276 (0.02%) 
Nerve root compression * 1  0/5279 (0.00%)