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The Evaluation of Bococizumab (PF-04950615;RN316) in Reducing the Occurrence of Major Cardiovascular Events in High Risk Subjects (SPIRE-1)

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ClinicalTrials.gov Identifier: NCT01975376
Recruitment Status : Terminated (See Detailed Description)
First Posted : November 4, 2013
Results First Posted : June 12, 2018
Last Update Posted : July 11, 2018
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 16784
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Placebo Bococizumab (PF-04950615)
Hide Arm/Group Description Participants received single dose of placebo matched to PF-04950615 subcutaneous injection once every 2 weeks for upto 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 every 2 weeks for upto 3 years. Participants were followed up to 40 days after the last dose.
Period Title: Overall Study
Started 8390 8394
Treated 8374 8386
Completed 8164 8177
Not Completed 226 217
Reason Not Completed
Adverse Event             5             5
Death             65             72
Lost to Follow-up             70             66
Withdrew consent             68             62
Other             2             4
Randomized, Not Treated             16             8
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 every 2 weeks for upto 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 every 2 weeks for upto 3 years. Participants were followed up to 40 days after the last dose. Total of all reporting groups
Overall Number of Baseline Participants 8390 8394 16784
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 8390 participants 8394 participants 16784 participants
63.3  (9.2) 63.3  (9.1) 63.3  (9.1)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 8390 participants 8394 participants 16784 participants
Female
2223
  26.5%
2207
  26.3%
4430
  26.4%
Male
6167
  73.5%
6187
  73.7%
12354
  73.6%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 8390 participants 8394 participants 16784 participants
Hispanic or Latino
1758
  21.0%
1746
  20.8%
3504
  20.9%
Not Hispanic or Latino
6631
  79.0%
6642
  79.1%
13273
  79.1%
Unknown or Not Reported
1
   0.0%
6
   0.1%
7
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 8390 participants 8394 participants 16784 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
354
   4.2%
369
   4.4%
723
   4.3%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
392
   4.7%
412
   4.9%
804
   4.8%
White
7315
  87.2%
7280
  86.7%
14595
  87.0%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
329
   3.9%
333
   4.0%
662
   3.9%
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 cardiovascular 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)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (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 every 2 weeks for upto 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 every 2 weeks for upto 3 years. Participants were followed up to 40 days after the last dose.
Overall Number of Participants Analyzed 8390 8394
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Events Per 100 Participant-Years
3.02
(2.59 to 3.51)
3.01
(2.58 to 3.50)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Bococizumab (PF-04950615)
Comments Hazard ratio and 95 percent (%) Confidence Interval (CI) were from a Cox proportional hazards model stratified by geographic region and low density lipoprotein cholesterol (LDL-C) at pre-screening (less than [<] 100 milligrams per deciliters [mg/dL], greater than and equal to [>=] 100 mg/dL) with treatment as a co-variate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.930905
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.99
Confidence Interval (2-Sided) 95%
0.80 to 1.22
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Event Rate Per 100 Participant-Years For First Occurrence of Composite Endpoint of Cardiovascular Death, Non-Fatal Myocardial Infraction, 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. Cardiovascular 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 cardiovascular 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 the CV death, non-fatal MI or non-fatal stroke (maximum duration: up to 3.4 years)
Show Outcome Measure DataHide 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 every 2 weeks for upto 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 every 2 weeks for upto 3 years. Participants were followed up to 40 days after the last dose.
Overall Number of Participants Analyzed 8390 8394
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Events Per 100 Participant-Years
2.49
(2.10 to 2.93)
2.59
(2.19 to 3.04)
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 from a Cox proportional hazards model stratified by geographic region and LDL-C at pre-screening (<100 mg/dL, >=100 mg/dL) with treatment as a covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.784265
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.03
Confidence Interval (2-Sided) 95%
0.82 to 1.30
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, 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)
Show Outcome Measure DataHide 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 every 2 weeks for upto 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 every 2 weeks for upto 3 years. Participants were followed up to 40 days after the last dose.
Overall Number of Participants Analyzed 8390 8394
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Events Per 100 Participant-Years
3.51
(3.04 to 4.03)
3.48
(3.02 to 4.00)
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 from a Cox proportional hazards model stratified by geographic region and LDL-C at pre-screening (<100 mg/dL, >=100 mg/dL) with treatment as a covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.892441
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.99
Confidence Interval (2-Sided) 95%
0.81 to 1.20
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, 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 the all-cause death, non-fatal MI, or non-fatal stroke (maximum duration: up to 3.4 years)
Show Outcome Measure DataHide 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 every 2 weeks for upto 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 every 2 weeks for upto 3 years. Participants were followed up to 40 days after the last dose.
Overall Number of Participants Analyzed 8390 8394
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Events Per 100 Participant-Years
2.98
(2.55 to 3.46)
3.06
(2.62 to 3.54)
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 from a Cox proportional hazards model stratified by geographic region and LDL-C at pre-screening (<100 mg/dL, >=100 mg/dL) with treatment as a covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.845797
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.02
Confidence Interval (2-Sided) 95%
0.83 to 1.26
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)
Show Outcome Measure DataHide 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 every 2 weeks for upto 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 every 2 weeks for upto 3 years. Participants were followed up to 40 days after the last dose.
Overall Number of Participants Analyzed 8390 8394
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Events Per 100 Participant-Years
0.57
(0.39 to 0.80)
0.47
(0.31 to 0.68)
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 from a Cox proportional hazards model stratified by geographic region and LDL-C at pre-screening (<100 mg/dL, >=100 mg/dL) with treatment as a covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.431903
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%
0.49 to 1.36
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Event Rate Per 100 Participant-Years For First Occurrence of Composite Endpoint of Cardiovascular Death, Non-Fatal Myocardial Infarction, Non-Fatal Stroke and Hospitalization for Unstable Angina
Hide Description Event rate per 100 participant-years for first occurrence of composite endpoint of cardiovascular death, non-fatal MI, non-fatal stroke and hospitalization for unstable angina (adjudicated by adjudication committee) was reported. Cardiovascular 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 cardiovascular 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 cardiovascular death, non-fatal MI, non-fatal stroke and hospitalization for unstable angina (maximum duration: up to 3.4 years)
Show Outcome Measure DataHide 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 every 2 weeks for upto 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 every 2 weeks for upto 3 years. Participants were followed up to 40 days after the last dose.
Overall Number of Participants Analyzed 8390 8394
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Events Per 100 Participant-Years
3.22
(2.77 to 3.72)
3.19
(2.74 to 3.69)
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 from a Cox proportional hazards model stratified by geographic region and LDL-C at pre-screening (<100 mg/dL, >=100 mg/dL) with treatment as a covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.883797
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.98
Confidence Interval (2-Sided) 95%
0.80 to 1.21
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Event Rate Per 100 Participant-Years For Cardiovascular Death
Hide Description Event rate per 100 participant-years for cardiovascular death (adjudicated by adjudication committee) was reported. Cardiovascular 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 cardiovascular 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 cardiovascular death (maximum duration: up to 3.4 years)
Show Outcome Measure DataHide 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 every 2 weeks for upto 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 every 2 weeks for upto 3 years. Participants were followed up to 40 days after the last dose.
Overall Number of Participants Analyzed 8390 8394
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Events Per 100 Participant-Years
0.52
(0.35 to 0.74)
0.64
(0.45 to 0.88)
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 from a Cox proportional hazards model stratified by geographic region and LDL-C at pre-screening (<100 mg/dL, >=100 mg/dL) with treatment as a covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.455690
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.20
Confidence Interval (2-Sided) 95%
0.74 to 1.95
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 MI (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 MI (fatal or non-fatal) (maximum duration: up to 3.4 years)
Show Outcome Measure DataHide 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 every 2 weeks for upto 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 every 2 weeks for upto 3 years. Participants were followed up to 40 days after the last dose.
Overall Number of Participants Analyzed 8390 8394
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Events Per 100 Participant-Years
1.56
(1.26 to 1.92)
1.74
(1.41 to 2.11)
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 from a Cox proportional hazards model stratified by geographic region and LDL-C at pre-screening (<100 mg/dL, >=100 mg/dL) with treatment as a covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.469496
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.11
Confidence Interval (2-Sided) 95%
0.84 to 1.48
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Event Rate Per 100 Participant-Years For Fatal Myocardial Infarction
Hide Description Event rate per 100 participant-years for 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)
Show Outcome Measure DataHide 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 every 2 weeks for upto 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 every 2 weeks for upto 3 years. Participants were followed up to 40 days after the last dose.
Overall Number of Participants Analyzed 8390 8394
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Events Per 100 Participant-Years
0.03
(0.00 to 0.12)
0.05
(0.01 to 0.15)
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 from a Cox proportional hazards model stratified by geographic region and LDL-C at pre-screening (<100 mg/dL, >=100 mg/dL) with treatment as a covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.633022
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.54
Confidence Interval (2-Sided) 95%
0.26 to 9.23
Estimation Comments [Not Specified]
10.Secondary Outcome
Title Event Rate Per 100 Participant-Years For First Occurrence of Non-Fatal Myocardial Infarction
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)
Show Outcome Measure DataHide 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 every 2 weeks for upto 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 every 2 weeks for upto 3 years. Participants were followed up to 40 days after the last dose.
Overall Number of Participants Analyzed 8390 8394
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Events Per 100 Participant-Years
1.53
(1.23 to 1.88)
1.70
(1.38 to 2.07)
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 from a Cox proportional hazards model stratified by geographic region and LDL-C at pre-screening (<100 mg/dL, >=100 mg/dL) with treatment as a covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.467650
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.11
Confidence Interval (2-Sided) 95%
0.83 to 1.48
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)
Show Outcome Measure DataHide 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 every 2 weeks for upto 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 every 2 weeks for upto 3 years. Participants were followed up to 40 days after the last dose.
Overall Number of Participants Analyzed 8390 8394
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Events Per 100 Participant-Years
0.71
(0.51 to 0.96)
0.38
(0.24 to 0.57)
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 from a Cox proportional hazards model stratified by geographic region and LDL-C at pre-screening (<100 mg/dL, >=100 mg/dL) with treatment as a covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.015462
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.53
Confidence Interval (2-Sided) 95%
0.32 to 0.89
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)
Show Outcome Measure DataHide 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 every 2 weeks for upto 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 every 2 weeks for upto 3 years. Participants were followed up to 40 days after the last dose.
Overall Number of Participants Analyzed 8390 8394
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Events Per 100 Participant-Years
0.79
(0.58 to 1.06)
0.43
(0.28 to 0.64)
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 from a Cox proportional hazards model stratified by geographic region and LDL-C at pre-screening (<100 mg/dL, >=100 mg/dL) with treatment as a covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.011863
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.54
Confidence Interval (2-Sided) 95%
0.33 to 0.88
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 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 fatal stroke (maximum duration: up to 3.4 years)
Show Outcome Measure DataHide 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 every 2 weeks for upto 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 every 2 weeks for upto 3 years. Participants were followed up to 40 days after the last dose.
Overall Number of Participants Analyzed 8390 8394
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Events Per 100 Participant-Years
0.10
(0.04 to 0.22)
0.05
(0.01 to 0.15)
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 from a Cox proportional hazards model stratified by geographic region and LDL-C at pre-screening (<100 mg/dL, >=100 mg/dL) with treatment as a covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.316066
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.50
Confidence Interval (2-Sided) 95%
0.12 to 2.00
Estimation Comments [Not Specified]
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)
Show Outcome Measure DataHide 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 every 2 weeks for upto 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 every 2 weeks for upto 3 years. Participants were followed up to 40 days after the last dose.
Overall Number of Participants Analyzed 8390 8394
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Events Per 100 Participant-Years
0.62
(0.44 to 0.86)
0.33
(0.20 to 0.51)
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 from a Cox proportional hazards model stratified by geographic region and LDL-C at pre-screening (<100 mg/dL, >=100 mg/dL) with treatment as a covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.020328
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.52
Confidence Interval (2-Sided) 95%
0.30 to 0.91
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)
Show Outcome Measure DataHide 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 every 2 weeks for upto 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 every 2 weeks for upto 3 years. Participants were followed up to 40 days after the last dose.
Overall Number of Participants Analyzed 8390 8394
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Events Per 100 Participant-Years
0.78
(0.57 to 1.04)
0.64
(0.45 to 0.88)
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 from a Cox proportional hazards model stratified by geographic region and LDL-C at pre-screening (<100 mg/dL, >=100 mg/dL) with treatment as a covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.367069
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%
0.53 to 1.27
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 congestive heart failure (maximum duration: up to 3.4 years)
Show Outcome Measure DataHide 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 every 2 weeks for upto 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 every 2 weeks for upto 3 years. Participants were followed up to 40 days after the last dose.
Overall Number of Participants Analyzed 8390 8394
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Events Per 100 Participant-Years
0.81
(0.60 to 1.08)
0.69
(0.49 to 0.94)
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 from a Cox proportional hazards model stratified by geographic region and LDL-C at pre-screening (<100 mg/dL, >=100 mg/dL) with treatment as a covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.443081
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.85
Confidence Interval (2-Sided) 95%
0.56 to 1.29
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)
Show Outcome Measure DataHide 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 every 2 weeks for upto 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 every 2 weeks for upto 3 years. Participants were followed up to 40 days after the last dose.
Overall Number of Participants Analyzed 8390 8394
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Events Per 100 Participant-Years
2.74
(2.33 to 3.20)
2.45
(2.06 to 2.89)
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 from a Cox proportional hazards model stratified by geographic region and LDL-C at pre-screening (<100 mg/dL, >=100 mg/dL) with treatment as a covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.343817
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%
0.71 to 1.12
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)
Show Outcome Measure DataHide 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 every 2 weeks for upto 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 every 2 weeks for upto 3 years. Participants were followed up to 40 days after the last dose.
Overall Number of Participants Analyzed 8390 8394
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Events Per 100 Participant-Years
0.40
(0.25 to 0.60)
0.41
(0.26 to 0.61)
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 from a Cox proportional hazards model stratified by geographic region and LDL-C at pre-screening (<100 mg/dL, >=100 mg/dL) with treatment as a covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.889065
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.04
Confidence Interval (2-Sided) 95%
0.59 to 1.85
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)
Show Outcome Measure DataHide 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 every 2 weeks for upto 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 every 2 weeks for upto 3 years. Participants were followed up to 40 days after the last dose.
Overall Number of Participants Analyzed 8390 8394
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Events Per 100 Participant-Years
2.37
(1.99 to 2.80)
2.08
(1.73 to 2.49)
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 from a Cox proportional hazards model stratified by geographic region and LDL-C at pre-screening (<100 mg/dL, >=100 mg/dL) with treatment as a covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.308388
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.88
Confidence Interval (2-Sided) 95%
0.69 to 1.13
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)
Show Outcome Measure DataHide 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 every 2 weeks for upto 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 every 2 weeks for upto 3 years. Participants were followed up to 40 days after the last dose.
Overall Number of Participants Analyzed 8390 8394
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Events Per 100 Participant-Years
1.26
(0.99 to 1.59)
1.28
(1.00 to 1.61)
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 from a Cox proportional hazards model stratified by geographic region and LDL-C at pre-screening (<100 mg/dL, >=100 mg/dL) with treatment as a covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.874835
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.03
Confidence Interval (2-Sided) 95%
0.74 to 1.42
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 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)
Show Outcome Measure DataHide 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 every 2 weeks for upto 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 every 2 weeks for upto 3 years. Participants were followed up to 40 days after the last dose.
Overall Number of Participants Analyzed 8390 8394
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Events Per 100 Participant-Years
1.00
(0.76 to 1.29)
1.13
(0.88 to 1.44)
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 from a Cox proportional hazards model stratified by geographic region and LDL-C at pre-screening (<100 mg/dL, >=100 mg/dL) with treatment as a covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.526269
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.12
Confidence Interval (2-Sided) 95%
0.79 to 1.60
Estimation Comments [Not Specified]
22.Secondary Outcome
Title Percent Change From Baseline in Low Density Lipoprotein Cholesterol at Week 14
Hide Description [Not Specified]
Time Frame Baseline, Week 14
Show Outcome Measure DataHide 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 every 2 weeks for upto 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 every 2 weeks for upto 3 years. Participants were followed up to 40 days after the last dose.
Overall Number of Participants Analyzed 6448 6439
Least Squares Mean (Standard Error)
Unit of Measure: Percent change
3.40  (0.31) -57.17  (0.31)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Bococizumab (PF-04950615)
Comments Lease Square (LS)- mean differences, associated 95% CI, and p-values were from a 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 LDL-C at pre-screening (<100 mg/dL, >=100 mg/dL).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Effect Model Repeat Measurement
Comments [Not Specified]
Method of Estimation Estimation Parameter LS-mean difference
Estimated Value -60.57
Confidence Interval (2-Sided) 95%
-61.43 to -59.71
Estimation Comments [Not Specified]
23.Secondary Outcome
Title Nominal Change From Baseline in Low Density Lipoprotein Cholesterol at Week 14
Hide Description [Not Specified]
Time Frame Baseline, Week 14
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on FAS. Here, "N" signifies number of 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 every 2 weeks for upto 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 every 2 weeks for upto 3 years. Participants were followed up to 40 days after the last dose.
Overall Number of Participants Analyzed 6448 6439
Least Squares Mean (Standard Error)
Unit of Measure: mg/dL
2.33  (0.28) -52.37  (0.28)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Bococizumab (PF-04950615)
Comments LS- mean differences and 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 LDL-C at pre-screening (<100 mg/dL, >=100 mg/dL).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Effect Model Repeat Measurement
Comments [Not Specified]
Method of Estimation Estimation Parameter LS-mean difference
Estimated Value -54.70
Confidence Interval (2-Sided) 95%
-55.48 to -53.92
Estimation Comments [Not Specified]
24.Secondary Outcome
Title Percent Change From Baseline in Low Density Lipoprotein Cholesterol at Last Post-Baseline Measurement
Hide Description [Not Specified]
Time Frame Baseline, last post-baseline measurement (any time up to Week 140)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on FAS. Here, "N" signifies number of 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 every 2 weeks for upto 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 every 2 weeks for upto 3 years. Participants were followed up to 40 days after the last dose.
Overall Number of Participants Analyzed 8240 8254
Least Squares Mean (Standard Error)
Unit of Measure: Percent Change
5.05  (0.35) -41.67  (0.35)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Bococizumab (PF-04950615)
Comments LS- mean difference and 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 LDL-C at pre-screening (<100 mg/dL, >=100 mg/dL).
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 -46.72
Confidence Interval (2-Sided) 95%
-47.68 to -45.76
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), total cholesterol, very low density lipoprotein cholesterol (VLDL-C), remnant lipoprotein cholesterol (RLP-C), apolipoprotein B (Apo B), HDL-C and apolipoprotein A-I (Apo A-I).
Time Frame Baseline, Week 14
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on FAS. 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 every 2 weeks for upto 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 every 2 weeks for upto 3 years. Participants were followed up to 40 days after the last dose.
Overall Number of Participants Analyzed 8390 8394
Least Squares Mean (Standard Error)
Unit of Measure: Percent Change
Non - HDL-C Number Analyzed 6427 participants 6412 participants
3.21  (0.28) -51.66  (0.28)
Total cholesterol Number Analyzed 6441 participants 6431 participants
2.38  (0.20) -34.13  (0.20)
VLDL - C Number Analyzed 6443 participants 6433 participants
6.52  (0.45) -13.65  (0.45)
RLP - C Number Analyzed 6418 participants 6400 participants
9.23  (0.79) -21.02  (0.79)
Apo B Number Analyzed 5887 participants 5894 participants
2.80  (0.31) -55.76  (0.31)
HDL - C Number Analyzed 6431 participants 6412 participants
1.19  (0.16) 7.33  (0.16)
Apo A - I Number Analyzed 5890 participants 5896 participants
1.21  (0.18) 4.74  (0.18)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Bococizumab (PF-04950615)
Comments Non-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 LDL-C at pre-screening (<100 mg/dL, >=100 mg/dL).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Effect Model Repeat Measurement
Comments [Not Specified]
Method of Estimation Estimation Parameter LS-mean difference
Estimated Value -54.88
Confidence Interval (2-Sided) 95%
-55.66 to -54.09
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
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 LDL-C at pre-screening (<100 mg/dL, >=100 mg/dL).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Effect Model Repeat Measurement
Comments [Not Specified]
Method of Estimation Estimation Parameter LS-mean difference
Estimated Value -36.51
Confidence Interval (2-Sided) 95%
-37.07 to -35.95
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
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 LDL-C at pre-screening (<100 mg/dL, >=100 mg/dL).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Effect Model Repeat Measurement
Comments [Not Specified]
Method of Estimation Estimation Parameter LS-mean difference
Estimated Value -20.17
Confidence Interval (2-Sided) 95%
-21.42 to -18.93
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
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 LDL-C at pre-screening (<100 mg/dL, >=100 mg/dL).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Effect Model Repeat Measurement
Comments [Not Specified]
Method of Estimation Estimation Parameter LS-Mean Difference
Estimated Value -30.25
Confidence Interval (2-Sided) 95%
-32.44 to -28.07
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
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 LDL-C at pre-screening (<100 mg/dL, >=100 mg/dL).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Effect Model Repeat Measurement
Comments [Not Specified]
Method of Estimation Estimation Parameter LS-Mean Difference
Estimated Value -58.55
Confidence Interval (2-Sided) 95%
-59.42 to -57.69
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
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 LDL-C at pre-screening (<100 mg/dL, >=100 mg/dL).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Effect Model Repeat Measurement
Comments [Not Specified]
Method of Estimation Estimation Parameter LS-Mean Difference
Estimated Value 6.14
Confidence Interval (2-Sided) 95%
5.69 to 6.59
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
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 LDL-C at pre-screening (<100 mg/dL, >=100 mg/dL).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Effect Model Repeat Measurement
Comments [Not Specified]
Method of Estimation Estimation Parameter LS-Mean Difference
Estimated Value 3.53
Confidence Interval (2-Sided) 95%
3.02 to 4.03
Estimation Comments [Not Specified]
26.Secondary Outcome
Title Percent Change From Baseline in Log-Transformed Lipoprotein (a) (Lp[a]) and Triglycerides at Week 14
Hide Description [Not Specified]
Time Frame Baseline, Week 14
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on FAS. 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 every 2 weeks for upto 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 every 2 weeks for upto 3 years. Participants were followed up to 40 days after the last dose.
Overall Number of Participants Analyzed 8390 8394
Mean (Standard Deviation)
Unit of Measure: Percent Change
Lp (a) Number Analyzed 5914 participants 5916 participants
-1.3  (28.81) -33.9  (29.62)
Triglycerides Number Analyzed 6443 participants 6433 participants
0.6  (32.84) -18.9  (28.44)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Bococizumab (PF-04950615)
Comments Lp (a): LS- mean differences and associated 95% CI, and p-values were from an MMRM model on the difference of log-transformed observations through Week 52 with fixed effects for treatment group, visit, treatment group*visit interaction, log-transformed baseline value, log-transformed baseline value*visit interaction, geographical region and LDL-C at pre-screening (<100 mg/dL, >=100 mg/dL).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Effect Model Repeat Measurement
Comments [Not Specified]
Method of Estimation Estimation Parameter LS-mean difference
Estimated Value 0.67
Confidence Interval (2-Sided) 95%
0.66 to 0.68
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Bococizumab (PF-04950615)
Comments Triglycerides: LS- mean differences and associated 95% CI, and p-values were from an MMRM model 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 LDL-C at pre-screening (<100 mg/dL, >=100 mg/dL).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Effect Model Repeat Measurement
Comments [Not Specified]
Method of Estimation Estimation Parameter LS-mean difference
Estimated Value 0.81
Confidence Interval (2-Sided) 95%
0.80 to 0.81
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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on FAS. Here, "N" signifies number of 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 every 2 weeks for upto 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 every 2 weeks for upto 3 years. Participants were followed up to 40 days after the last dose.
Overall Number of Participants Analyzed 5931 5930
Mean (Standard Deviation)
Unit of Measure: Percent change
-6.5  (88.28) -1.1  (91.91)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Bococizumab (PF-04950615)
Comments LS- mean differences and associated 95% CI, and p-values were from an MMRM model on the difference of log-transformed observations through Week 52 with fixed effects for treatment group, visit, treatment group*visit interaction, log-transformed baseline value, log-transformed baseline value*visit interaction, geographical region and LDL-C at pre-screening (<100 mg/dL, >=100 mg/dL).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Effect Model Repeat Measurement
Comments [Not Specified]
Method of Estimation Estimation Parameter LS-mean difference
Estimated Value 1.06
Confidence Interval (2-Sided) 95%
1.03 to 1.10
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 every 2 weeks for upto 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 every 2 weeks for upto 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   65/8374 (0.78%)   72/8386 (0.86%) 
Show Serious Adverse Events Hide Serious Adverse Events
Placebo Bococizumab (PF-04950615)
Affected / at Risk (%) Affected / at Risk (%)
Total   986/8374 (11.77%)   1060/8386 (12.64%) 
Blood and lymphatic system disorders     
Anaemia * 1  8/8374 (0.10%)  6/8386 (0.07%) 
Haemorrhagic anaemia * 1  1/8374 (0.01%)  2/8386 (0.02%) 
Iron deficiency anaemia * 1  1/8374 (0.01%)  2/8386 (0.02%) 
Leukocytosis * 1  2/8374 (0.02%)  1/8386 (0.01%) 
Lymphadenopathy * 1  1/8374 (0.01%)  1/8386 (0.01%) 
Pancytopenia * 1  1/8374 (0.01%)  1/8386 (0.01%) 
Cardiac disorders     
Acute coronary syndrome * 1  8/8374 (0.10%)  11/8386 (0.13%) 
Acute left ventricular failure * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Acute myocardial infarction * 1  29/8374 (0.35%)  40/8386 (0.48%) 
Angina pectoris * 1  52/8374 (0.62%)  73/8386 (0.87%) 
Angina unstable * 1  84/8374 (1.00%)  65/8386 (0.78%) 
Aortic valve stenosis * 1  2/8374 (0.02%)  2/8386 (0.02%) 
Arrhythmia * 1  1/8374 (0.01%)  3/8386 (0.04%) 
Arteriosclerosis coronary artery * 1  4/8374 (0.05%)  2/8386 (0.02%) 
Atrial fibrillation * 1  32/8374 (0.38%)  27/8386 (0.32%) 
Atrial flutter * 1  9/8374 (0.11%)  3/8386 (0.04%) 
Atrial tachycardia * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Atrial thrombosis * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Atrioventricular block complete * 1  1/8374 (0.01%)  4/8386 (0.05%) 
Atrioventricular block second degree * 1  1/8374 (0.01%)  1/8386 (0.01%) 
Bradycardia * 1  3/8374 (0.04%)  7/8386 (0.08%) 
Cardiac arrest * 1  3/8374 (0.04%)  8/8386 (0.10%) 
Cardiac discomfort * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Cardiac disorder * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Cardiac failure * 1  19/8374 (0.23%)  21/8386 (0.25%) 
Cardiac failure acute * 1  2/8374 (0.02%)  3/8386 (0.04%) 
Cardiac failure chronic * 1  1/8374 (0.01%)  2/8386 (0.02%) 
Cardiac failure congestive * 1  32/8374 (0.38%)  24/8386 (0.29%) 
Cardio-respiratory arrest * 1  1/8374 (0.01%)  1/8386 (0.01%) 
Cardiogenic shock * 1  1/8374 (0.01%)  4/8386 (0.05%) 
Coronary artery disease * 1  31/8374 (0.37%)  30/8386 (0.36%) 
Coronary artery dissection * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Coronary artery insufficiency * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Coronary artery occlusion * 1  5/8374 (0.06%)  1/8386 (0.01%) 
Coronary artery stenosis * 1  4/8374 (0.05%)  5/8386 (0.06%) 
Heart valve incompetence * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Ischaemic cardiomyopathy * 1  2/8374 (0.02%)  4/8386 (0.05%) 
Left ventricular failure * 1  1/8374 (0.01%)  2/8386 (0.02%) 
Microvascular coronary artery disease * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Myocardial infarction * 1  32/8374 (0.38%)  35/8386 (0.42%) 
Myocardial ischaemia * 1  6/8374 (0.07%)  6/8386 (0.07%) 
Palpitations * 1  2/8374 (0.02%)  2/8386 (0.02%) 
Pericardial effusion * 1  0/8374 (0.00%)  2/8386 (0.02%) 
Pericarditis * 1  1/8374 (0.01%)  1/8386 (0.01%) 
Sinus bradycardia * 1  0/8374 (0.00%)  2/8386 (0.02%) 
Sinus node dysfunction * 1  0/8374 (0.00%)  2/8386 (0.02%) 
Sinus tachycardia * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Stress cardiomyopathy * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Supraventricular tachycardia * 1  1/8374 (0.01%)  6/8386 (0.07%) 
Tachyarrhythmia * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Tachycardia * 1  1/8374 (0.01%)  2/8386 (0.02%) 
Ventricular arrhythmia * 1  0/8374 (0.00%)  2/8386 (0.02%) 
Ventricular dysfunction * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Ventricular fibrillation * 1  0/8374 (0.00%)  3/8386 (0.04%) 
Ventricular tachycardia * 1  9/8374 (0.11%)  4/8386 (0.05%) 
Congenital, familial and genetic disorders     
Hereditary haemorrhagic telangiectasia * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Ear and labyrinth disorders     
Deafness unilateral * 1  2/8374 (0.02%)  0/8386 (0.00%) 
Eustachian tube dysfunction * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Vertigo * 1  4/8374 (0.05%)  3/8386 (0.04%) 
Vestibular disorder * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Endocrine disorders     
Hyperparathyroidism * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Hypothyroidism * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Thyroid mass * 1  0/8374 (0.00%)  2/8386 (0.02%) 
Eye disorders     
Angle closure glaucoma * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Cataract * 1  2/8374 (0.02%)  1/8386 (0.01%) 
Diabetic retinopathy * 1  1/8374 (0.01%)  1/8386 (0.01%) 
Lens dislocation * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Macular fibrosis * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Optic ischaemic neuropathy * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Retinal artery occlusion * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Retinal detachment * 1  3/8374 (0.04%)  1/8386 (0.01%) 
Retinal exudates * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Visual impairment * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Vitreous haemorrhage * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Gastrointestinal disorders     
Abdominal discomfort * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Abdominal distension * 1  1/8374 (0.01%)  1/8386 (0.01%) 
Abdominal hernia * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Abdominal hernia obstructive * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Abdominal pain * 1  7/8374 (0.08%)  1/8386 (0.01%) 
Abdominal pain lower * 1  1/8374 (0.01%)  1/8386 (0.01%) 
Abdominal pain upper * 1  1/8374 (0.01%)  2/8386 (0.02%) 
Abdominal wall haematoma * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Anal polyp * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Anal prolapse * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Appendix disorder * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Ascites * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Chronic gastritis * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Colitis * 1  2/8374 (0.02%)  1/8386 (0.01%) 
Colitis ischaemic * 1  1/8374 (0.01%)  1/8386 (0.01%) 
Colonic pseudo-obstruction * 1  1/8374 (0.01%)  1/8386 (0.01%) 
Constipation * 1  1/8374 (0.01%)  3/8386 (0.04%) 
Dental caries * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Diarrhoea * 1  2/8374 (0.02%)  1/8386 (0.01%) 
Diverticulum intestinal * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Diverticulum intestinal haemorrhagic * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Duodenitis * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Dyspepsia * 1  1/8374 (0.01%)  1/8386 (0.01%) 
Enteritis * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Food poisoning * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Gastric haemorrhage * 1  2/8374 (0.02%)  0/8386 (0.00%) 
Gastric perforation * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Gastric polyps * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Gastric ulcer * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Gastric ulcer haemorrhage * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Gastritis * 1  0/8374 (0.00%)  3/8386 (0.04%) 
Gastritis erosive * 1  1/8374 (0.01%)  1/8386 (0.01%) 
Gastroduodenitis * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Gastrointestinal haemorrhage * 1  6/8374 (0.07%)  5/8386 (0.06%) 
Gastrointestinal necrosis * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Gastrointestinal polyp haemorrhage * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Gastrooesophageal reflux disease * 1  0/8374 (0.00%)  3/8386 (0.04%) 
Gingival bleeding * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Haematemesis * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Haemorrhoidal haemorrhage * 1  1/8374 (0.01%)  1/8386 (0.01%) 
Haemorrhoids * 1  1/8374 (0.01%)  1/8386 (0.01%) 
Hiatus hernia * 1  0/8374 (0.00%)  2/8386 (0.02%) 
Ileus * 1  1/8374 (0.01%)  1/8386 (0.01%) 
Impaired gastric emptying * 1  1/8374 (0.01%)  3/8386 (0.04%) 
Incarcerated umbilical hernia * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Inguinal hernia * 1  3/8374 (0.04%)  10/8386 (0.12%) 
Intestinal haemorrhage * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Intestinal ischaemia * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Intestinal obstruction * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Intestinal strangulation * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Large intestine polyp * 1  0/8374 (0.00%)  3/8386 (0.04%) 
Lower gastrointestinal haemorrhage * 1  1/8374 (0.01%)  2/8386 (0.02%) 
Mechanical ileus * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Melaena * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Necrotising colitis * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Obstruction gastric * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Oesophageal spasm * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Oesophageal stenosis * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Oesophagitis * 1  1/8374 (0.01%)  3/8386 (0.04%) 
Pancreatitis * 1  1/8374 (0.01%)  1/8386 (0.01%) 
Pancreatitis acute * 1  6/8374 (0.07%)  5/8386 (0.06%) 
Peptic ulcer perforation * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Rectal haemorrhage * 1  2/8374 (0.02%)  2/8386 (0.02%) 
Rectal polyp * 1  0/8374 (0.00%)  2/8386 (0.02%) 
Salivary gland enlargement * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Short-bowel syndrome * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Small intestinal obstruction * 1  1/8374 (0.01%)  1/8386 (0.01%) 
Small intestinal stenosis * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Thrombosis mesenteric vessel * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Tongue oedema * 1  1/8374 (0.01%)  1/8386 (0.01%) 
Ulcerative gastritis * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Umbilical hernia * 1  1/8374 (0.01%)  2/8386 (0.02%) 
Upper gastrointestinal haemorrhage * 1  1/8374 (0.01%)  2/8386 (0.02%) 
Vomiting * 1  2/8374 (0.02%)  0/8386 (0.00%) 
General disorders     
Asthenia * 1  3/8374 (0.04%)  0/8386 (0.00%) 
Cardiac death * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Chest pain * 1  16/8374 (0.19%)  15/8386 (0.18%) 
Death * 1  10/8374 (0.12%)  15/8386 (0.18%) 
Electrocution * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Fatigue * 1  0/8374 (0.00%)  1/8386 (0.01%) 
General physical health deterioration * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Generalised oedema * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Hyperplasia * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Ill-defined disorder * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Impaired healing * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Inflammation * 1  2/8374 (0.02%)  0/8386 (0.00%) 
Injection site hypersensitivity * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Injection site reaction * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Mucosal inflammation * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Multiple organ dysfunction syndrome * 1  3/8374 (0.04%)  3/8386 (0.04%) 
Necrosis * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Non-cardiac chest pain * 1  47/8374 (0.56%)  45/8386 (0.54%) 
Oedema peripheral * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Pain * 1  0/8374 (0.00%)  2/8386 (0.02%) 
Pelvic mass * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Pyrexia * 1  1/8374 (0.01%)  3/8386 (0.04%) 
Sudden cardiac death * 1  1/8374 (0.01%)  3/8386 (0.04%) 
Sudden death * 1  5/8374 (0.06%)  5/8386 (0.06%) 
Systemic inflammatory response syndrome * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Vascular stent restenosis * 1  1/8374 (0.01%)  4/8386 (0.05%) 
Vascular stent thrombosis * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Hepatobiliary disorders     
Bile duct stenosis * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Bile duct stone * 1  0/8374 (0.00%)  2/8386 (0.02%) 
Biliary colic * 1  1/8374 (0.01%)  1/8386 (0.01%) 
Biliary dyskinesia * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Cholangitis * 1  0/8374 (0.00%)  2/8386 (0.02%) 
Cholecystitis * 1  8/8374 (0.10%)  8/8386 (0.10%) 
Cholecystitis acute * 1  2/8374 (0.02%)  5/8386 (0.06%) 
Cholecystitis chronic * 1  1/8374 (0.01%)  2/8386 (0.02%) 
Cholecystocholangitis * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Cholelithiasis * 1  3/8374 (0.04%)  8/8386 (0.10%) 
Drug-induced liver injury * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Hepatic cirrhosis * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Hepatic failure * 1  1/8374 (0.01%)  1/8386 (0.01%) 
Hepatitis * 1  1/8374 (0.01%)  1/8386 (0.01%) 
Non-alcoholic fatty liver * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Immune system disorders     
Anaphylactic shock * 1  1/8374 (0.01%)  1/8386 (0.01%) 
Hypersensitivity * 1  0/8374 (0.00%)  3/8386 (0.04%) 
Infections and infestations     
Abdominal abscess * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Abdominal wall abscess * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Abscess limb * 1  0/8374 (0.00%)  2/8386 (0.02%) 
Abscess neck * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Acute sinusitis * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Anal abscess * 1  1/8374 (0.01%)  3/8386 (0.04%) 
Appendicitis * 1  7/8374 (0.08%)  2/8386 (0.02%) 
Arthritis bacterial * 1  1/8374 (0.01%)  1/8386 (0.01%) 
Arthritis infective * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Bacterial sepsis * 1  1/8374 (0.01%)  1/8386 (0.01%) 
Bronchitis * 1  8/8374 (0.10%)  1/8386 (0.01%) 
Bursitis infective * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Bursitis infective staphylococcal * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Carbuncle * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Cellulitis * 1  13/8374 (0.16%)  11/8386 (0.13%) 
Cellulitis of male external genital organ * 1 [1]  0/6158 (0.00%)  1/6180 (0.02%) 
Clostridium colitis * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Clostridium difficile colitis * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Clostridium difficile infection * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Creutzfeldt-Jakob disease * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Cystitis * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Dermo-hypodermitis * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Diabetic foot infection * 1  1/8374 (0.01%)  4/8386 (0.05%) 
Diverticulitis * 1  7/8374 (0.08%)  5/8386 (0.06%) 
Emphysematous pyelonephritis * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Endocarditis * 1  2/8374 (0.02%)  1/8386 (0.01%) 
Endocarditis bacterial * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Endocarditis enterococcal * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Endometritis * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Epididymitis * 1  2/8374 (0.02%)  0/8386 (0.00%) 
Erysipelas * 1  3/8374 (0.04%)  4/8386 (0.05%) 
Furuncle * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Gangrene * 1  2/8374 (0.02%)  3/8386 (0.04%) 
Gastritis viral * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Gastroenteritis * 1  9/8374 (0.11%)  3/8386 (0.04%) 
Gastroenteritis bacterial * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Gastroenteritis salmonella * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Gastroenteritis viral * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Groin abscess * 1  1/8374 (0.01%)  1/8386 (0.01%) 
H1N1 influenza * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Haematoma infection * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Hepatitis E * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Herpes zoster * 1  2/8374 (0.02%)  0/8386 (0.00%) 
Incision site infection * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Infected bite * 1  2/8374 (0.02%)  0/8386 (0.00%) 
Infected fistula * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Infected seroma * 1  2/8374 (0.02%)  0/8386 (0.00%) 
Infected skin ulcer * 1  1/8374 (0.01%)  1/8386 (0.01%) 
Infectious pleural effusion * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Infective exacerbation of chronic obstructive airways disease * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Influenza * 1  0/8374 (0.00%)  3/8386 (0.04%) 
Kidney infection * 1  2/8374 (0.02%)  0/8386 (0.00%) 
Klebsiella sepsis * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Localised infection * 1  1/8374 (0.01%)  3/8386 (0.04%) 
Lower respiratory tract infection * 1  2/8374 (0.02%)  2/8386 (0.02%) 
Lower respiratory tract infection viral * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Lung infection * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Lyme disease * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Nasopharyngitis * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Orchitis * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Osteomyelitis * 1  0/8374 (0.00%)  8/8386 (0.10%) 
Osteomyelitis bacterial * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Osteomyelitis chronic * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Otitis media * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Paronychia * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Penile infection * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Periodontitis * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Perirectal abscess * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Peritonitis * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Pneumonia * 1  39/8374 (0.47%)  34/8386 (0.41%) 
Pneumonia bacterial * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Pneumonia viral * 1  2/8374 (0.02%)  0/8386 (0.00%) 
Post procedural cellulitis * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Post procedural infection * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Post procedural pneumonia * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Prostatic abscess * 1 [1]  1/6158 (0.02%)  0/6180 (0.00%) 
Pyelonephritis * 1  2/8374 (0.02%)  1/8386 (0.01%) 
Pyelonephritis acute * 1  0/8374 (0.00%)  2/8386 (0.02%) 
Pyomyositis * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Rectal abscess * 1  1/8374 (0.01%)  1/8386 (0.01%) 
Respiratory tract infection * 1  1/8374 (0.01%)  1/8386 (0.01%) 
Sepsis * 1  8/8374 (0.10%)  7/8386 (0.08%) 
Sepsis syndrome * 1  2/8374 (0.02%)  0/8386 (0.00%) 
Septic shock * 1  5/8374 (0.06%)  2/8386 (0.02%) 
Skin candida * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Skin infection * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Staphylococcal bacteraemia * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Staphylococcal infection * 1  1/8374 (0.01%)  2/8386 (0.02%) 
Streptococcal infection * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Subcutaneous abscess * 1  0/8374 (0.00%)  2/8386 (0.02%) 
Superinfection * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Tonsillitis * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Tracheitis * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Tracheobronchitis * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Tuberculosis * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Upper respiratory tract infection * 1  0/8374 (0.00%)  3/8386 (0.04%) 
Urinary tract infection * 1  13/8374 (0.16%)  15/8386 (0.18%) 
Urosepsis * 1  5/8374 (0.06%)  3/8386 (0.04%) 
Vestibular neuronitis * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Viral infection * 1  1/8374 (0.01%)  1/8386 (0.01%) 
Viral sepsis * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Viral upper respiratory tract infection * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Visceral leishmaniasis * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Wound infection * 1  1/8374 (0.01%)  1/8386 (0.01%) 
Wound infection staphylococcal * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Injury, poisoning and procedural complications     
Acetabulum fracture * 1  1/8374 (0.01%)  1/8386 (0.01%) 
Anaemia postoperative * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Animal bite * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Ankle fracture * 1  2/8374 (0.02%)  2/8386 (0.02%) 
Arterial injury * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Brain herniation * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Burns second degree * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Cardiac function disturbance postoperative * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Cerebral ventricle collapse * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Chest injury * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Clavicle fracture * 1  2/8374 (0.02%)  1/8386 (0.01%) 
Concussion * 1  2/8374 (0.02%)  1/8386 (0.01%) 
Contusion * 1  1/8374 (0.01%)  2/8386 (0.02%) 
Coronary vascular graft occlusion * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Craniocerebral injury * 1  1/8374 (0.01%)  2/8386 (0.02%) 
Eye injury * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Fall * 1  3/8374 (0.04%)  6/8386 (0.07%) 
Femoral neck fracture * 1  1/8374 (0.01%)  3/8386 (0.04%) 
Femur fracture * 1  0/8374 (0.00%)  4/8386 (0.05%) 
Foot fracture * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Gastrointestinal anastomotic leak * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Gun shot wound * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Head injury * 1  2/8374 (0.02%)  1/8386 (0.01%) 
Heat exhaustion * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Hip fracture * 1  5/8374 (0.06%)  5/8386 (0.06%) 
Humerus fracture * 1  1/8374 (0.01%)  2/8386 (0.02%) 
Incisional hernia * 1  2/8374 (0.02%)  1/8386 (0.01%) 
Intentional overdose * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Joint dislocation * 1  1/8374 (0.01%)  1/8386 (0.01%) 
Laceration * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Ligament rupture * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Limb injury * 1  3/8374 (0.04%)  0/8386 (0.00%) 
Lower limb fracture * 1  1/8374 (0.01%)  2/8386 (0.02%) 
Mallet finger * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Meniscus injury * 1  0/8374 (0.00%)  2/8386 (0.02%) 
Multiple fractures * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Multiple injuries * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Muscle rupture * 1  1/8374 (0.01%)  1/8386 (0.01%) 
Muscle strain * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Overdose * 1  1/8374 (0.01%)  1/8386 (0.01%) 
Patella fracture * 1  1/8374 (0.01%)  1/8386 (0.01%) 
Pelvic fracture * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Peripheral artery restenosis * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Post concussion syndrome * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Post procedural complication * 1  0/8374 (0.00%)  2/8386 (0.02%) 
Post procedural haematoma * 1  1/8374 (0.01%)  1/8386 (0.01%) 
Post procedural haemorrhage * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Post procedural oedema * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Postoperative delirium * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Postoperative thoracic procedure complication * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Procedural complication * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Procedural haemorrhage * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Procedural hypertension * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Procedural pain * 1  2/8374 (0.02%)  0/8386 (0.00%) 
Pubis fracture * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Radius fracture * 1  1/8374 (0.01%)  1/8386 (0.01%) 
Rib fracture * 1  4/8374 (0.05%)  4/8386 (0.05%) 
Road traffic accident * 1  7/8374 (0.08%)  1/8386 (0.01%) 
Seroma * 1  1/8374 (0.01%)  1/8386 (0.01%) 
Skin abrasion * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Skull fracture * 1  0/8374 (0.00%)  2/8386 (0.02%) 
Soft tissue injury * 1  2/8374 (0.02%)  0/8386 (0.00%) 
Spinal column injury * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Spinal compression fracture * 1  1/8374 (0.01%)  3/8386 (0.04%) 
Spinal fracture * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Subarachnoid haemorrhage * 1  2/8374 (0.02%)  0/8386 (0.00%) 
Subdural haematoma * 1  4/8374 (0.05%)  3/8386 (0.04%) 
Tendon injury * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Tendon rupture * 1  3/8374 (0.04%)  2/8386 (0.02%) 
Thermal burn * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Thoracic vertebral fracture * 1  1/8374 (0.01%)  1/8386 (0.01%) 
Tibia fracture * 1  2/8374 (0.02%)  0/8386 (0.00%) 
Toxicity to various agents * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Traumatic intracranial haemorrhage * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Ulna fracture * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Upper limb fracture * 1  4/8374 (0.05%)  1/8386 (0.01%) 
Vascular bypass dysfunction * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Vascular graft occlusion * 1  2/8374 (0.02%)  0/8386 (0.00%) 
Vascular pseudoaneurysm * 1  2/8374 (0.02%)  1/8386 (0.01%) 
Vena cava injury * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Wound * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Wound dehiscence * 1  1/8374 (0.01%)  1/8386 (0.01%) 
Wrist fracture * 1  0/8374 (0.00%)  2/8386 (0.02%) 
Investigations     
Alanine aminotransferase increased * 1  1/8374 (0.01%)  2/8386 (0.02%) 
Aspartate aminotransferase increased * 1  1/8374 (0.01%)  2/8386 (0.02%) 
Blood creatine phosphokinase increased * 1  1/8374 (0.01%)  2/8386 (0.02%) 
Blood glucose decreased * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Blood glucose increased * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Blood pressure decreased * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Blood pressure diastolic decreased * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Cardiac stress test abnormal * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Electrocardiogram abnormal * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Gamma-glutamyltransferase increased * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Heart rate abnormal * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Hepatic enzyme increased * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Hepatitis C virus test positive * 1  0/8374 (0.00%)  1/8386 (0.01%) 
International normalised ratio abnormal * 1  0/8374 (0.00%)  1/8386 (0.01%) 
International normalised ratio decreased * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Liver function test abnormal * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Liver function test increased * 1  0/8374 (0.00%)  5/8386 (0.06%) 
Stress echocardiogram abnormal * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Weight decreased * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Metabolism and nutrition disorders     
Dehydration * 1  4/8374 (0.05%)  7/8386 (0.08%) 
Diabetes mellitus * 1  0/8374 (0.00%)  4/8386 (0.05%) 
Diabetes mellitus inadequate control * 1  4/8374 (0.05%)  2/8386 (0.02%) 
Diabetes with hyperosmolarity * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Diabetic ketoacidosis * 1  4/8374 (0.05%)  0/8386 (0.00%) 
Fluid overload * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Gout * 1  2/8374 (0.02%)  0/8386 (0.00%) 
Hyperglycaemia * 1  0/8374 (0.00%)  5/8386 (0.06%) 
Hyperkalaemia * 1  3/8374 (0.04%)  1/8386 (0.01%) 
Hyperosmolar hyperglycaemic state * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Hypervolaemia * 1  1/8374 (0.01%)  1/8386 (0.01%) 
Hypoglycaemia * 1  5/8374 (0.06%)  2/8386 (0.02%) 
Hypokalaemia * 1  1/8374 (0.01%)  3/8386 (0.04%) 
Hypomagnesaemia * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Hyponatraemia * 1  1/8374 (0.01%)  1/8386 (0.01%) 
Hypovolaemia * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Insulin-requiring type 2 diabetes mellitus * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Ketoacidosis * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Lactic acidosis * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Metabolic acidosis * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Obesity * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Type 2 diabetes mellitus * 1  4/8374 (0.05%)  4/8386 (0.05%) 
Vitamin B12 deficiency * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Musculoskeletal and connective tissue disorders     
Arthralgia * 1  2/8374 (0.02%)  1/8386 (0.01%) 
Arthritis * 1  3/8374 (0.04%)  6/8386 (0.07%) 
Arthropathy * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Back pain * 1  5/8374 (0.06%)  5/8386 (0.06%) 
Bone lesion * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Bursitis * 1  1/8374 (0.01%)  1/8386 (0.01%) 
Cervical spinal stenosis * 1  3/8374 (0.04%)  1/8386 (0.01%) 
Costochondritis * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Diabetic arthropathy * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Gouty arthritis * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Intervertebral disc degeneration * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Intervertebral disc disorder * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Intervertebral disc protrusion * 1  6/8374 (0.07%)  4/8386 (0.05%) 
Knee deformity * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Lumbar spinal stenosis * 1  0/8374 (0.00%)  4/8386 (0.05%) 
Muscle tightness * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Muscular weakness * 1  2/8374 (0.02%)  0/8386 (0.00%) 
Musculoskeletal chest pain * 1  3/8374 (0.04%)  10/8386 (0.12%) 
Musculoskeletal pain * 1  1/8374 (0.01%)  3/8386 (0.04%) 
Myalgia * 1  1/8374 (0.01%)  1/8386 (0.01%) 
Neck pain * 1  1/8374 (0.01%)  1/8386 (0.01%) 
Osteoarthritis * 1  18/8374 (0.21%)  22/8386 (0.26%) 
Osteolysis * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Osteonecrosis * 1  1/8374 (0.01%)  1/8386 (0.01%) 
Osteoporotic fracture * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Pain in extremity * 1  2/8374 (0.02%)  2/8386 (0.02%) 
Rhabdomyolysis * 1  1/8374 (0.01%)  2/8386 (0.02%) 
Rheumatoid arthritis * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Rotator cuff syndrome * 1  3/8374 (0.04%)  6/8386 (0.07%) 
Spinal column stenosis * 1  2/8374 (0.02%)  3/8386 (0.04%) 
Spinal osteoarthritis * 1  3/8374 (0.04%)  2/8386 (0.02%) 
Spinal pain * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Spondylitis * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Spondylolisthesis * 1  1/8374 (0.01%)  1/8386 (0.01%) 
Synovial cyst * 1  0/8374 (0.00%)  2/8386 (0.02%) 
Tendonitis * 1  1/8374 (0.01%)  1/8386 (0.01%) 
Trigger finger * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Adenocarcinoma * 1  1/8374 (0.01%)  1/8386 (0.01%) 
Adenocarcinoma gastric * 1  0/8374 (0.00%)  3/8386 (0.04%) 
Adenocarcinoma of colon * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Anal squamous cell carcinoma * 1  0/8374 (0.00%)  1/8386 (0.01%) 
B-cell lymphoma * 1  2/8374 (0.02%)  0/8386 (0.00%) 
Benign gastrointestinal neoplasm * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Bile duct cancer * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Bladder cancer * 1  5/8374 (0.06%)  4/8386 (0.05%) 
Bladder cancer recurrent * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Bladder neoplasm * 1  0/8374 (0.00%)  3/8386 (0.04%) 
Bladder papilloma * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Bladder transitional cell carcinoma * 1  3/8374 (0.04%)  0/8386 (0.00%) 
Bladder transitional cell carcinoma stage I * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Bone cancer * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Breast cancer * 1  2/8374 (0.02%)  3/8386 (0.04%) 
Breast cancer recurrent * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Cholesteatoma * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Chronic myelomonocytic leukaemia * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Clear cell renal cell carcinoma * 1  2/8374 (0.02%)  0/8386 (0.00%) 
Colon cancer * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Colon cancer metastatic * 1  0/8374 (0.00%)  2/8386 (0.02%) 
Colon cancer stage III * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Colorectal cancer * 1  2/8374 (0.02%)  0/8386 (0.00%) 
Gastric adenoma * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Gastric cancer * 1  1/8374 (0.01%)  1/8386 (0.01%) 
Gastrointestinal stromal tumour * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Gastrointestinal tract adenoma * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Gastrooesophageal cancer * 1  2/8374 (0.02%)  0/8386 (0.00%) 
Glioblastoma multiforme * 1  0/8374 (0.00%)  2/8386 (0.02%) 
Intestinal adenocarcinoma * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Intraocular melanoma * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Large cell lung cancer * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Laryngeal cancer * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Lip and/or oral cavity cancer stage 0 * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Lipoma * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Liposarcoma * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Lung adenocarcinoma * 1  2/8374 (0.02%)  0/8386 (0.00%) 
Lung adenocarcinoma metastatic * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Lung cancer metastatic * 1  2/8374 (0.02%)  0/8386 (0.00%) 
Lung neoplasm * 1  2/8374 (0.02%)  1/8386 (0.01%) 
Lung neoplasm malignant * 1  3/8374 (0.04%)  5/8386 (0.06%) 
Lung squamous cell carcinoma stage III * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Lymphoma * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Malignant melanoma * 1  3/8374 (0.04%)  3/8386 (0.04%) 
Maxillofacial sinus neoplasm * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Meningioma * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Mesothelioma * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Metastases to bone * 1  1/8374 (0.01%)  2/8386 (0.02%) 
Metastases to liver * 1  1/8374 (0.01%)  4/8386 (0.05%) 
Metastases to lymph nodes * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Metastases to peritoneum * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Metastases to spine * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Metastatic malignant melanoma * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Metastatic neoplasm * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Metastatic squamous cell carcinoma * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Nasal neoplasm * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Neuroendocrine carcinoma * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Non-small cell lung cancer * 1  1/8374 (0.01%)  1/8386 (0.01%) 
Oesophageal adenocarcinoma * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Ovarian adenoma * 1 [1]  0/2216 (0.00%)  1/2206 (0.05%) 
Pancreatic carcinoma * 1  2/8374 (0.02%)  2/8386 (0.02%) 
Pancreatic neoplasm * 1  1/8374 (0.01%)  1/8386 (0.01%) 
Plasma cell myeloma * 1  1/8374 (0.01%)  3/8386 (0.04%) 
Prostate cancer * 1 [1]  12/6158 (0.19%)  13/6180 (0.21%) 
Prostate cancer metastatic * 1 [1]  1/6158 (0.02%)  1/6180 (0.02%) 
Prostatic adenoma * 1 [1]  1/6158 (0.02%)  0/6180 (0.00%) 
Rectal adenoma * 1  2/8374 (0.02%)  0/8386 (0.00%) 
Rectal cancer * 1  1/8374 (0.01%)  2/8386 (0.02%) 
Renal cancer * 1  4/8374 (0.05%)  1/8386 (0.01%) 
Renal cancer recurrent * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Renal cell carcinoma * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Small cell lung cancer * 1  1/8374 (0.01%)  1/8386 (0.01%) 
Soft tissue neoplasm * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Squamous cell carcinoma * 1  2/8374 (0.02%)  2/8386 (0.02%) 
Squamous cell carcinoma of lung * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Squamous cell carcinoma of the cervix * 1 [1]  1/2216 (0.05%)  0/2206 (0.00%) 
Tonsil cancer * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Transitional cell carcinoma * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Uterine leiomyoma * 1 [1]  2/2216 (0.09%)  1/2206 (0.05%) 
Nervous system disorders     
Axonal neuropathy * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Balance disorder * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Basal ganglia haemorrhage * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Brain stem infarction * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Carotid arteriosclerosis * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Carotid artery disease * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Carotid artery occlusion * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Carotid artery stenosis * 1  8/8374 (0.10%)  14/8386 (0.17%) 
Carpal tunnel syndrome * 1  0/8374 (0.00%)  2/8386 (0.02%) 
Cauda equina syndrome * 1  1/8374 (0.01%)  1/8386 (0.01%) 
Cerebellar haemorrhage * 1  1/8374 (0.01%)  1/8386 (0.01%) 
Cerebellar infarction * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Cerebral artery occlusion * 1  2/8374 (0.02%)  0/8386 (0.00%) 
Cerebral haematoma * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Cerebral haemorrhage * 1  2/8374 (0.02%)  3/8386 (0.04%) 
Cerebral infarction * 1  1/8374 (0.01%)  3/8386 (0.04%) 
Cerebral venous thrombosis * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Cerebrovascular accident * 1  6/8374 (0.07%)  3/8386 (0.04%) 
Cervical radiculopathy * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Chorea * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Coma * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Cubital tunnel syndrome * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Diabetic neuropathy * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Dizziness * 1  3/8374 (0.04%)  8/8386 (0.10%) 
Embolic stroke * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Encephalopathy * 1  2/8374 (0.02%)  0/8386 (0.00%) 
Epilepsy * 1  0/8374 (0.00%)  4/8386 (0.05%) 
Facial paresis * 1  1/8374 (0.01%)  2/8386 (0.02%) 
Haemorrhage intracranial * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Haemorrhagic cerebral infarction * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Haemorrhagic stroke * 1  2/8374 (0.02%)  2/8386 (0.02%) 
Headache * 1  1/8374 (0.01%)  4/8386 (0.05%) 
Hemiparesis * 1  1/8374 (0.01%)  3/8386 (0.04%) 
Hypoaesthesia * 1  1/8374 (0.01%)  1/8386 (0.01%) 
Hypoglycaemic coma * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Intraventricular haemorrhage * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Ischaemic stroke * 1  28/8374 (0.33%)  20/8386 (0.24%) 
Lacunar infarction * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Lacunar stroke * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Loss of consciousness * 1  3/8374 (0.04%)  0/8386 (0.00%) 
Lumbar radiculopathy * 1  1/8374 (0.01%)  1/8386 (0.01%) 
Lumbosacral radiculopathy * 1  0/8374 (0.00%)  2/8386 (0.02%) 
Migraine * 1  0/8374 (0.00%)  1/8386 (0.01%) 
Nerve compression * 1  3/8374 (0.04%)  0/8386 (0.00%) 
Nervous system disorder * 1  1/8374 (0.01%)  0/8386 (0.00%) 
Paraesthesia * 1