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A Comparison of Prasugrel and Clopidogrel in Acute Coronary Syndrome Subjects (TRILOGY ACS)

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ClinicalTrials.gov Identifier: NCT00699998
Recruitment Status : Completed
First Posted : June 18, 2008
Results First Posted : May 7, 2013
Last Update Posted : May 7, 2013
Sponsor:
Collaborators:
Daiichi Sankyo Co., Ltd.
Duke Clinical Research Institute
Information provided by (Responsible Party):
Eli Lilly and Company

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Acute Coronary Syndrome
Interventions Drug: Clopidogrel
Drug: Prasugrel
Drug: Commercially-available Aspirin
Enrollment 9326
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Prasugrel: <75 Years of Age Prasugrel: 75 Years of Age or Older Clopidogrel: <75 Years of Age Clopidogrel: 75 Years of Age or Older
Hide Arm/Group Description

Prasugrel and Low-dose Commercially-available Aspirin in participants less than (<) 75 years of age.

Commercially-available Aspirin: Low-dose aspirin, oral, as prescribed by physician through end of study.

Prasugrel: 30 milligram (mg), oral, once as loading dose (in those subjects who initiate study drug with a loading dose); and either 5 mg or 10 mg (based upon weight) orally, once daily as maintenance dose through end of study.

Prasugrel and Low-dose Commercially-available Aspirin in participants 75 years of age or older.

Commercially-available Aspirin: Low-dose aspirin, oral, as prescribed by physician through end of study.

Prasugrel: 30 milligram (mg), oral, once as loading dose (in those subjects who initiate study drug with a loading dose); and 5 mg orally, once daily as maintenance dose through end of study.

Clopidogrel and Low-Dose Commercially-available Aspirin in participants less than (<) 75 years of age.

Commercially-available Aspirin : Low-dose aspirin, oral, as prescribed by physician through end of study

Clopidogrel: 300 milligram (mg), oral, once as loading dose (in those subjects who initiate study drug with a loading dose); and 75 mg, oral, once daily as maintenance dose through end of study

Clopidogrel and Low-Dose Commercially-available Aspirin in participants 75 years of age or older.

Commercially-available Aspirin: Low-dose aspirin, oral, as prescribed by physician through end of study.

Clopidogrel: 300 milligram (mg), oral, once as loading dose (in those subjects who initiate study drug with a loading dose); and 75 mg, oral, once daily as maintenance dose through end of study.

Period Title: Overall Study
Started 3620 1043 3623 1040
Received at Least 1 Dose of Study Drug 3590 1033 3590 1027
Completed 3421 957 3417 958
Not Completed 199 86 206 82
Reason Not Completed
Withdrawal by Subject             194             83             202             80
Physician Decision             3             2             1             1
Lost to Follow-up             2             1             3             1
Arm/Group Title Prasugrel: <75 Years of Age Prasugrel: 75 Years of Age or Older Clopidogrel: <75 Years of Age Clopidogrel: 75 Years of Age or Older Total
Hide Arm/Group Description Prasugrel and Low-dose Commercially-available Aspirin in participants less than (<) 75 years of age. Commercially-available Aspirin: Low-dose aspirin, oral, as prescribed by physician through end of study. Prasugrel : 30 milligram (mg), oral, once as loading dose (in those subjects who initiate study drug with a loading dose); and either 5 mg or 10 mg (based upon weight) orally, once daily as maintenance dose through end of study. Prasugrel and Low-dose Commercially-available Aspirin in participants 75 years of age or older. Commercially-available Aspirin: Low-dose aspirin, oral, as prescribed by physician through end of study. Prasugrel: 30 milligram (mg), oral, once as loading dose (in those subjects who initiate study drug with a loading dose); and 5 mg orally, once daily as maintenance dose through end of study. Clopidogrel and Low-Dose Commercially-available Aspirin in participants less than (<) 75 years of age. Commercially-available Aspirin: Low-dose aspirin, oral, as prescribed by physician through end of study. Clopidogrel: 300 milligram (mg), oral, once as loading dose (in those subjects who initiate study drug with a loading dose); and 75 mg, oral, once daily as maintenance dose through end of study. Clopidogrel and Low-Dose Commercially-available Aspirin in participants 75 years of age or older. Commercially-available Aspirin: Low-dose aspirin, oral, as prescribed by physician through end of study. Clopidogrel: 300 milligram (mg), oral, once as loading dose (in those subjects who initiate study drug with a loading dose); and 75 mg, oral, once daily as maintenance dose through end of study. Total of all reporting groups
Overall Number of Baseline Participants 3620 1043 3623 1040 9326
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 3620 participants 1043 participants 3623 participants 1040 participants 9326 participants
61.4  (8.55) 80.3  (4.29) 61.5  (8.38) 80.3  (4.39) 65.7  (11.02)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3620 participants 1043 participants 3623 participants 1040 participants 9326 participants
Female
1309
  36.2%
520
  49.9%
1290
  35.6%
531
  51.1%
3650
  39.1%
Male
2311
  63.8%
523
  50.1%
2333
  64.4%
509
  48.9%
5676
  60.9%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 3620 participants 1043 participants 3623 participants 1040 participants 9326 participants
Caucasian 2362 767 2374 773 6276
African 87 14 72 12 185
Hispanic 321 109 346 86 862
Asian 821 147 800 164 1932
Other 29 6 30 5 70
Unknown 0 0 1 0 1
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 3620 participants 1043 participants 3623 participants 1040 participants 9326 participants
Portugal 18 11 14 11 54
Philippines 58 7 48 14 127
Taiwan 6 6 4 9 25
Slovakia 62 20 60 20 162
Greece 14 8 10 11 43
Costa Rica 5 1 2 2 10
Thailand 30 17 36 10 93
Ukraine 326 28 311 42 707
Chile 28 15 33 13 89
Italy 71 44 70 47 232
India 513 56 508 64 1141
France 29 22 29 19 99
Denmark 21 7 17 10 55
Korea, Republic of 35 7 33 7 82
Panama 29 7 24 10 70
Turkey 76 24 81 19 200
Czech Republic 37 31 32 38 138
Mexico 38 15 40 16 109
Canada 58 14 61 13 146
Brazil 154 27 147 34 362
Romania 103 26 105 23 257
Croatia 63 28 60 31 182
Sweden 4 3 6 1 14
United States 430 133 446 116 1125
Serbia 42 4 40 5 91
Spain 13 8 10 12 43
Ireland 5 4 6 3 18
Israel 75 33 85 21 214
Russian Federation 128 22 135 14 299
Colombia 40 21 45 17 123
Switzerland 6 4 4 6 20
Malaysia 35 7 33 9 84
Peru 58 19 67 12 156
Australia 13 6 15 7 41
South Africa 27 11 27 12 77
Netherlands 55 23 53 24 155
Tunisia 20 3 20 4 47
China 126 38 120 44 328
Finland 3 3 5 2 13
Lithuania 29 8 32 4 73
Austria 6 6 6 5 23
Malta 9 1 10 2 22
United Kingdom 33 21 40 12 106
Egypt 65 1 62 4 132
Hungary 86 43 87 44 260
Argentina 120 58 138 41 357
Poland 137 59 129 68 393
Belgium 7 7 7 8 29
Singapore 2 5 5 1 13
Bulgaria 216 48 209 55 528
Germany 46 20 46 21 133
New Zealand 10 3 10 3 26
History of Diabetes  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 3620 participants 1043 participants 3623 participants 1040 participants 9326 participants
Yes 1393 363 1418 365 3539
No 2221 678 2193 675 5767
Unknown 6 2 12 0 20
History of Myocardial Infarction (MI)  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 3620 participants 1043 participants 3623 participants 1040 participants 9326 participants
Yes 1556 426 1612 393 3987
No 2035 603 1988 633 5259
Unknown 29 14 23 14 80
History of Coronary Revascularization (PCI or CABG)   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 3620 participants 1043 participants 3623 participants 1040 participants 9326 participants
Yes 1279 330 1365 299 3273
No 2332 703 2239 734 6008
Unknown 9 10 19 7 45
[1]
Measure Description: History of Coronary Revascularization due to percutaneous coronary intervention (PCI) or coronary artery bypass graft surgery (CABG)
Clinical Presentation of UA or NSTEMI   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 3620 participants 1043 participants 3623 participants 1040 participants 9326 participants
Unstable Angina 963 166 981 192 2302
Non-ST-segment Elevation Myocardial Infarction 2453 829 2434 804 6520
Unknown/Did not meet criteria 204 48 208 44 504
[1]
Measure Description: Clinical Presentation of unstable angina (UA) or non-ST-segment elevation myocardial infarction (NSTEMI)
1.Primary Outcome
Title Percentage of Participants With a Composite Endpoint of Cardiovascular (CV) Death, Myocardial Infarction (MI), or Stroke
Hide Description The percentage of participants is the total number of participants experiencing a CV death, nonfatal MI, or nonfatal stroke divided by number of participants in the treatment arm multiplied by 100. Endpoint events were adjudicated by the Clinical Endpoint Committee.
Time Frame Randomization through end of study (30-month visit)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants
Arm/Group Title Prasugrel: <75 Years of Age Prasugrel: 75 Years of Age or Older Clopidogrel: <75 Years of Age Clopidogrel: 75 Years of Age or Older
Hide Arm/Group Description:
Prasugrel and Low-dose Commercially-available Aspirin in participants less than (<) 75 years of age. Commercially-available Aspirin: Low-dose aspirin, oral, as prescribed by physician through end of study Prasugrel: 30 milligram (mg), oral, once as loading dose (in those subjects who initiate study drug with a loading dose); and either 5 mg or 10 mg (based upon weight) orally, once daily as maintenance dose through end of study.
Prasugrel and Low-dose Commercially-available Aspirin in participants 75 years of age or older. Commercially-available Aspirin: Low-dose aspirin, oral, as prescribed by physician through end of study. Prasugrel: 30 milligram (mg), oral, once as loading dose (in those subjects who initiate study drug with a loading dose); and 5 mg orally, once daily as maintenance dose through end of study.
Clopidogrel and Low-Dose Commercially-available Aspirin in participants less than (<) 75 years of age. Commercially-available Aspirin: Low-dose aspirin, oral, as prescribed by physician through end of study. Clopidogrel: 300 milligram (mg), oral, once as loading dose (in those subjects who initiate study drug with a loading dose); and 75 mg, oral, once daily as maintenance dose through end of study.
Clopidogrel and Low-Dose Commercially-available Aspirin in participants 75 years of age or older. Commercially-available Aspirin: Low-dose aspirin, oral, as prescribed by physician through end of study. Clopidogrel: 300 milligram (mg), oral, once as loading dose (in those subjects who initiate study drug with a loading dose); and 75 mg, oral, once daily as maintenance dose through end of study.
Overall Number of Participants Analyzed 3620 1043 3623 1040
Measure Type: Number
Unit of Measure: percentage of participants with an event
10.06 24.64 10.96 24.13
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Prasugrel: <75 Years of Age, Clopidogrel: <75 Years of Age
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.210
Comments Two-sided p-value based on a log-rank test stratified by clopidogrel status at randomization.
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.915
Confidence Interval (2-Sided) 95%
0.793 to 1.055
Estimation Comments HR and two-sided 95% CI derived using Cox proportional hazards model with treatment and clopidogrel status at randomization as fixed effects.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Prasugrel: 75 Years of Age or Older, Clopidogrel: 75 Years of Age or Older
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.731
Comments Two-sided p-value based on a log-rank test stratified by clopidogrel status at randomization.
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.029
Confidence Interval (2-Sided) 95%
0.865 to 1.225
Estimation Comments HR and two-sided 95% CI derived using Cox proportional hazards model with treatment and clopidogrel status at randomization as fixed effects.
2.Secondary Outcome
Title Percentage of Participants With a Composite Endpoint of CV Death and MI
Hide Description The percentage of participants is the total number of participants experiencing a CV death or nonfatal MI divided by number of participants in the treatment arm. Endpoint events were adjudicated by the Clinical Endpoint Committee.
Time Frame Randomization through end of study (30-month visit)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants
Arm/Group Title Prasugrel: <75 Years of Age Prasugrel: 75 Years of Age or Older Clopidogrel: <75 Years of Age Clopidogrel: 75 Years of Age or Older
Hide Arm/Group Description:
Prasugrel and Low-dose Commercially-available Aspirin in participants less than (<) 75 years of age. Commercially-available Aspirin: Low-dose aspirin, oral, as prescribed by physician through end of study. Prasugrel: 30 milligram (mg), oral, once as loading dose (in those subjects who initiate study drug with a loading dose); and either 5 mg or 10 mg (based upon weight) orally, once daily as maintenance dose through end of study.
Prasugrel and Low-dose Commercially-available Aspirin in participants 75 years of age or older. Commercially-available Aspirin: Low-dose aspirin, oral, as prescribed by physician through end of study. Prasugrel: 30 milligram (mg), oral, once as loading dose (in those subjects who initiate study drug with a loading dose); and 5 mg orally, once daily as maintenance dose through end of study.
Clopidogrel and Low-Dose Commercially-available Aspirin in participants less than (<) 75 years of age. Commercially-available Aspirin: Low-dose aspirin, oral, as prescribed by physician through end of study. Clopidogrel: 300 milligram (mg), oral, once as loading dose (in those subjects who initiate study drug with a loading dose); and 75 mg, oral, once daily as maintenance dose through end of study.
Clopidogrel and Low-Dose Commercially-available Aspirin in participants 75 years of age or older. Commercially-available Aspirin: Low-dose aspirin, oral, as prescribed by physician through end of study. Clopidogrel: 300 milligram (mg), oral, once as loading dose (in those subjects who initiate study drug with a loading dose); and 75 mg, oral, once daily as maintenance dose through end of study.
Overall Number of Participants Analyzed 3620 1043 3623 1040
Measure Type: Number
Unit of Measure: percentage of participants with an event
9.61 22.53 10.21 22.69
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Prasugrel: <75 Years of Age, Clopidogrel: <75 Years of Age
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.388
Comments [Not Specified]
Method Log Rank
Comments Two-sided p-value based on a log-rank test stratified by clopidogrel status at randomization.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.940
Confidence Interval (2-Sided) 95%
0.812 to 1.088
Estimation Comments HR and two-sided 95% CI derived using Cox proportional hazards model with treatment and clopidogrel status at randomization as fixed effects.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Prasugrel: 75 Years of Age or Older, Clopidogrel: 75 Years of Age or Older
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.990
Comments Two-sided p-value based on a log-rank test stratified by clopidogrel status at randomization.
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.998
Confidence Interval (2-Sided) 95%
0.833 to 1.195
Estimation Comments HR and two-sided 95% CI derived using Cox proportional hazards model with treatment and clopidogrel status at randomization as fixed effects.
3.Secondary Outcome
Title Percentage of Participants With a Composite Endpoint of CV Death, MI, Stroke, or Re-hospitalization for Recurrent Unstable Angina (UA)
Hide Description The percentage of participants is the total number of participants experiencing a CV death, nonfatal MI, nonfatal stroke or re-hospitalization for a recurrent UA divided by number of participants in the treatment arm. Endpoints events were adjudicated by the Clinical Endpoint Committee.
Time Frame Randomization through end of study (30-month visit)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants
Arm/Group Title Prasugrel: <75 Years of Age Prasugrel: 75 Years of Age or Older Clopidogrel: <75 Years of Age Clopidogrel: 75 Years of Age or Older
Hide Arm/Group Description:
Prasugrel and Low-dose Commercially-available Aspirin in participants less than (<) 75 years of age. Commercially-available Aspirin: Low-dose aspirin, oral, as prescribed by physician through end of study. Prasugrel: 30 milligram (mg), oral, once as loading dose (in those subjects who initiate study drug with a loading dose); and either 5 mg or 10 mg (based upon weight) orally, once daily as maintenance dose through end of study.
Prasugrel and Low-dose Commercially-available Aspirin in participants 75 years of age or older. Commercially-available Aspirin: Low-dose aspirin, oral, as prescribed by physician through end of study. Prasugrel: 30 milligram (mg), oral, once as loading dose (in those subjects who initiate study drug with a loading dose); and 5 mg orally, once daily as maintenance dose through end of study.
Clopidogrel and Low-Dose Commercially-available Aspirin in participants less than (<) 75 years of age. Commercially-available Aspirin: Low-dose aspirin, oral, as prescribed by physician through end of study. Clopidogrel: 300 milligram (mg), oral, once as loading dose (in those subjects who initiate study drug with a loading dose); and 75 mg, oral, once daily as maintenance dose through end of study.
Clopidogrel and Low-Dose Commercially-available Aspirin in participants 75 years of age or older. Commercially-available Aspirin: Low-dose aspirin, oral, as prescribed by physician through end of study. Clopidogrel: 300 milligram (mg), oral, once as loading dose (in those subjects who initiate study drug with a loading dose); and 75 mg, oral, once daily as maintenance dose through end of study.
Overall Number of Participants Analyzed 3620 1043 3623 1040
Measure Type: Number
Unit of Measure: percentage of participants with an event
12.13 26.27 12.83 25.67
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Prasugrel: <75 Years of Age, Clopidogrel: <75 Years of Age
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.353
Comments Two-sided p-value based on a log-rank test stratified by clopidogrel status at randomization.
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.941
Confidence Interval (2-Sided) 95%
0.826 to 1.073
Estimation Comments HR and two-sided 95% CI derived using Cox proportional hazards model with treatment and clopidogrel status at randomization as fixed effects.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Prasugrel: 75 Years of Age or Older, Clopidogrel: 75 Years of Age or Older
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.719
Comments Two-sided p-value based on a log-rank test stratified by clopidogrel status at randomization.
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.029
Confidence Interval (2-Sided) 95%
0.869 to 1.218
Estimation Comments HR and two-sided 95% CI derived using Cox proportional hazards model with treatment and clopidogrel status at randomization as fixed effects.
4.Secondary Outcome
Title Percentage of Participants With a Composite Endpoint of All-cause Death, MI, or Stroke
Hide Description The percentage of participants is the total number of participants experiencing an all-cause death, nonfatal MI, or nonfatal stroke divided by number of participants in the treatment arm. Endpoint events were adjudicated by the Clinical Endpoint Committee.
Time Frame Randomization through end of study (30-month visit)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants
Arm/Group Title Prasugrel: <75 Years of Age Prasugrel: 75 Years of Age or Older Clopidogrel: <75 Years of Age Clopidogrel: 75 Years of Age or Older
Hide Arm/Group Description:
Prasugrel and Low-dose Commercially-available Aspirin in participants less than (<) 75 years of age. Commercially-available Aspirin: Low-dose aspirin, oral, as prescribed by physician through end of study. Prasugrel: 30 milligram (mg), oral, once as loading dose (in those subjects who initiate study drug with a loading dose); and either 5 mg or 10 mg (based upon weight) orally, once daily as maintenance dose through end of study.
Prasugrel and Low-dose Commercially-available Aspirin in participants 75 years of age or older. Commercially-available Aspirin: Low-dose aspirin, oral, as prescribed by physician through end of study. Prasugrel: 30 milligram (mg), oral, once as loading dose (in those subjects who initiate study drug with a loading dose); and 5 mg orally, once daily as maintenance dose through end of study.
Clopidogrel and Low-Dose Commercially-available Aspirin in participants less than (<) 75 years of age. Commercially-available Aspirin: Low-dose aspirin, oral, as prescribed by physician through end of study. Clopidogrel: 300 milligram (mg), oral, once as loading dose (in those subjects who initiate study drug with a loading dose); and 75 mg, oral, once daily as maintenance dose through end of study.
Clopidogrel and Low-Dose Commercially-available Aspirin in participants 75 years of age or older. Commercially-available Aspirin: Low-dose aspirin, oral, as prescribed by physician through end of study. Clopidogrel: 300 milligram (mg), oral, once as loading dose (in those subjects who initiate study drug with a loading dose); and 75 mg, oral, once daily as maintenance dose through end of study.
Overall Number of Participants Analyzed 3620 1043 3623 1040
Measure Type: Number
Unit of Measure: percentage of participants with an event
10.61 27.04 11.12 26.83
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Prasugrel: <75 Years of Age, Clopidogrel: <75 Years of Age
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.270
Comments Two-sided p-value based on a log-rank test stratified by clopidogrel status at randomization.
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.928
Confidence Interval (2-Sided) 95%
0.810 to 1.063
Estimation Comments HR and two-sided 95% CI derived using Cox proportional hazards model with treatment and clopidogrel status at randomization as fixed effects.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Prasugrel: 75 Years of Age or Older, Clopidogrel: 75 Years of Age or Older
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.831
Comments Two-sided p-value based on a log-rank test stratified by clopidogrel status at randomization.
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.017
Confidence Interval (2-Sided) 95%
0.862 to 1.200
Estimation Comments HR and two-sided 95% CI derived using Cox proportional hazards model with treatment and clopidogrel status at randomization as fixed effects.
5.Secondary Outcome
Title Platelet Aggregation Measures
Hide Description Platelet aggregation was measured by as measured by Accumetrics Verify Now™ P2Y12. Results were reported in P2Y12 Reaction Units (PRU). PRU represents the rate and extent of adenosine (ADP)-stimulated platelet aggregation. Lower values indicate greater P2Y12 platelet inhibition and lower platelet activity and aggregation. ANCOVA Model was used and values were corrected for treatment + baseline value + clopidogrel status at randomization.
Time Frame Day 30 and 12 Months
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least 1 dose of study drug, and had a baseline and post-baseline PRU measurement at Day 30 or Month 12.
Arm/Group Title Prasugrel: <75 Years of Age Prasugrel: 75 Years of Age or Older Clopidogrel: <75 Years of Age Clopidogrel: 75 Years of Age or Older
Hide Arm/Group Description:
Prasugrel and Low-dose Commercially-available Aspirin in participants less than (<) 75 years of age. Commercially-available Aspirin: Low-dose aspirin, oral, as prescribed by physician through end of study. Prasugrel: 30 milligram (mg), oral, once as loading dose (in those subjects who initiate study drug with a loading dose); and either 5 mg or 10 mg (based upon weight) orally, once daily as maintenance dose through end of study.
Prasugrel and Low-dose Commercially-available Aspirin in participants 75 years of age or older. Commercially-available Aspirin: Low-dose aspirin, oral, as prescribed by physician through end of study. Prasugrel: 30 milligram (mg), oral, once as loading dose (in those subjects who initiate study drug with a loading dose); and 5 mg orally, once daily as maintenance dose through end of study.
Clopidogrel and Low-Dose Commercially-available Aspirin in participants less than (<) 75 years of age. Commercially-available Aspirin: Low-dose aspirin, oral, as prescribed by physician through end of study. Clopidogrel: 300 milligram (mg), oral, once as loading dose (in those subjects who initiate study drug with a loading dose); and 75 mg, oral, once daily as maintenance dose through end of study.
Clopidogrel and Low-Dose Commercially-available Aspirin in participants 75 years of age or older. Commercially-available Aspirin: Low-dose aspirin, oral, as prescribed by physician through end of study. Clopidogrel: 300 milligram (mg), oral, once as loading dose (in those subjects who initiate study drug with a loading dose); and 75 mg, oral, once daily as maintenance dose through end of study.
Overall Number of Participants Analyzed 720 158 683 179
Least Squares Mean (Standard Error)
Unit of Measure: P2Y12 Reaction Units (PRU)
Day 30 93.280  (3.804) 151.872  (8.148) 193.489  (3.780) 200.285  (8.238)
Month 12 (n=386, 76, 400, 103) 94.529  (5.706) 135.096  (14.631) 199.003  (5.663) 181.360  (14.380)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Prasugrel: <75 Years of Age, Clopidogrel: <75 Years of Age
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments p-value is for Day 30 comparison. ANCOVA Model: Measurement = treatment + baseline value + clopidogrel status at randomization.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -100.208
Confidence Interval (2-Sided) 95%
-107.872 to -92.545
Estimation Comments Estimated Mean Difference (Final Values) for Day 30 comparison
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Prasugrel: <75 Years of Age, Clopidogrel: <75 Years of Age
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments p-value is for 12 month comparison. ANCOVA Model: Measurement = treatment + baseline value + clopidogrel status at randomization.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -104.475
Confidence Interval (2-Sided) 95%
-115.383 to -93.566
Estimation Comments Estimated Mean Difference (Final Values) for 12 month comparison.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Prasugrel: 75 Years of Age or Older, Clopidogrel: 75 Years of Age or Older
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments p-value is for 30 day comparison. ANCOVA Model: Measurement = treatment + baseline value + clopidogrel status at randomization.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -48.413
Confidence Interval (2-Sided) 95%
-63.718 to -33.108
Estimation Comments Estimated Mean Difference (Final Values) is for the 30 day comparison.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Prasugrel: 75 Years of Age or Older, Clopidogrel: 75 Years of Age or Older
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments p-value is for the 12 month comparison. ANCOVA Model: Measurement = treatment + baseline value + clopidogrel status at randomization.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -46.264
Confidence Interval (2-Sided) 95%
-69.061 to -23.468
Estimation Comments Estimated Mean Difference (Final Values) is for the 12 month comparison.
6.Secondary Outcome
Title Biomarker Measurements of Inflammation/Hemodynamic Stress: Brain Natriuretic Peptide (BNP)
Hide Description Brain natriuretic peptide (BNP) is secreted by the ventricles of the heart in response to hemodynamic stress and is a biomarker associated with increased CV risk. Results are presented as geometric least squares means (Geometric LS means). Geometric LS means were adjusted for treatment + baseline value + clopidogrel status at randomization.
Time Frame Day 30 and 6 Months
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least 1 dose of study therapy and had baseline and post-baseline BNP measurement at Day 30 or 6 Months.
Arm/Group Title Prasugrel: <75 Years of Age Prasugrel: 75 Years of Age or Older Clopidogrel: <75 Years of Age Clopidogrel: 75 Years of Age or Older
Hide Arm/Group Description:
Prasugrel and Low-dose Commercially-available Aspirin in participants less than (<) 75 years of age. Commercially-available Aspirin: Low-dose aspirin, oral, as prescribed by physician through end of study. Prasugrel: 30 milligram (mg), oral, once as loading dose (in those subjects who initiate study drug with a loading dose); and either 5 mg or 10 mg (based upon weight) orally, once daily as maintenance dose through end of study.
Prasugrel and Low-dose Commercially-available Aspirin in participants 75 years of age or older. Commercially-available Aspirin: Low-dose aspirin, oral, as prescribed by physician through end of study. Prasugrel: 30 milligram (mg), oral, once as loading dose (in those subjects who initiate study drug with a loading dose); and 5 mg orally, once daily as maintenance dose through end of study.
Clopidogrel and Low-Dose Commercially-available Aspirin in participants less than (<) 75 years of age. Commercially-available Aspirin: Low-dose aspirin, oral, as prescribed by physician through end of study. Clopidogrel: 300 milligram (mg), oral, once as loading dose (in those subjects who initiate study drug with a loading dose); and 75 mg, oral, once daily as maintenance dose through end of study.
Clopidogrel and Low-Dose Commercially-available Aspirin in participants 75 years of age or older. Commercially-available Aspirin: Low-dose aspirin, oral, as prescribed by physician through end of study. Clopidogrel: 300 milligram (mg), oral, once as loading dose (in those subjects who initiate study drug with a loading dose); and 75 mg, oral, once daily as maintenance dose through end of study.
Overall Number of Participants Analyzed 859 196 840 224
Geometric Mean (Standard Error)
Unit of Measure: picograms per milliliter (pg/mL)
Day 30 313.494  (1.039) 1082.396  (1.093) 319.345  (1.039) 951.359  (1.092)
6 Months (n=725, 125, 701, 174) 253.434  (1.049) 770.132  (1.135) 250.982  (1.049) 722.750  (1.130)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Prasugrel: <75 Years of Age, Clopidogrel: <75 Years of Age
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.631
Comments p-value is for the 30 day comparison. ANCOVA Model: Measurement = treatment + baseline value + clopidogrel status at randomization.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric Ratio Estimate
Estimated Value 0.982
Confidence Interval (2-Sided) 95%
0.910 to 1.059
Estimation Comments Geometric Ratio Estimate is for the 30 day comparison.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Prasugrel: <75 Years of Age, Clopidogrel: <75 Years of Age
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.844
Comments p-value is for the 6 month comparison. ANCOVA Model: Measurement = treatment + baseline value + clopidogrel status at randomization.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric Ratio Estimate
Estimated Value 1.010
Confidence Interval (2-Sided) 95%
0.916 to 1.113
Estimation Comments Geometric Ratio Estimate is for the 6 month comparison.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Prasugrel: 75 Years of Age or Older, Clopidogrel: 75 Years of Age or Older
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.098
Comments p-value is for the 30 day comparison. ANCOVA Model: Measurement = treatment + baseline value + clopidogrel status at randomization.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric Ratio Estimate
Estimated Value 1.138
Confidence Interval (2-Sided) 95%
0.977 to 1.325
Estimation Comments Geometric Ratio Estimate is for the 30 day comparison.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Prasugrel: 75 Years of Age or Older, Clopidogrel: 75 Years of Age or Older
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.545
Comments p-value is for the 6 month comparison. ANCOVA Model: Measurement = treatment + baseline value + clopidogrel status at randomization.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric Ratio Estimate
Estimated Value 1.066
Confidence Interval (2-Sided) 95%
0.867 to 1.310
Estimation Comments Geometric Ratio Estimate is for the 6 month comparison.
7.Secondary Outcome
Title Biomarker Measurements of Inflammation/Hemodynamic Stress: C-Reactive Protein (CRP)
Hide Description C-Reactive Protein (CRP) is a biomarker associated with inflammation and increased CV risk. Results are presented as geometric least squares means (Geometric LS means). Geometric LS means were adjusted for treatment + baseline value + clopidogrel status at randomization.
Time Frame Day 30 and Month 6
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least 1 dose of study therapy and had baseline and post-baseline CRP measurement at Day 30 or 6 Months.
Arm/Group Title Prasugrel: <75 Years of Age Prasugrel: 75 Years of Age or Older Clopidogrel: <75 Years of Age Clopidogrel: 75 Years of Age or Older
Hide Arm/Group Description:
Prasugrel and Low-dose Commercially-available Aspirin in participants less than (<) 75 years of age. Commercially-available Aspirin: Low-dose aspirin, oral, as prescribed by physician through end of study Prasugrel: 30 milligram (mg), oral, once as loading dose (in those subjects who initiate study drug with a loading dose); and either 5 mg or 10 mg (based upon weight) orally, once daily as maintenance dose through end of study.
Prasugrel and Low-dose Commercially-available Aspirin in participants 75 years of age or older. Commercially-available Aspirin: Low-dose aspirin, oral, as prescribed by physician through end of study. Prasugrel: 30 milligram (mg), oral, once as loading dose (in those subjects who initiate study drug with a loading dose); and 5 mg orally, once daily as maintenance dose through end of study.
Clopidogrel and Low-Dose Commercially-available Aspirin in participants less than (<) 75 years of age. Commercially-available Aspirin: Low-dose aspirin, oral, as prescribed by physician through end of study. Clopidogrel: 300 milligram (mg), oral, once as loading dose (in those subjects who initiate study drug with a loading dose); and 75 mg, oral, once daily as maintenance dose through end of study.
Clopidogrel and Low-Dose Commercially-available Aspirin in participants 75 years of age or older. Commercially-available Aspirin: Low-dose aspirin, oral, as prescribed by physician through end of study. Clopidogrel: 300 milligram (mg), oral, once as loading dose (in those subjects who initiate study drug with a loading dose); and 75 mg, oral, once daily as maintenance dose through end of study.
Overall Number of Participants Analyzed 888 209 863 226
Geometric Mean (Standard Error)
Unit of Measure: milligrams per liter (mg/L)
Day 30 2.330  (1.053) 2.441  (1.150) 2.287  (1.053) 2.226  (1.150)
6 Months (n=755, 143, 745, 178) 2.272  (1.060) 1.593  (1.173) 2.149  (1.059) 1.543  (1.170)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Prasugrel: <75 Years of Age, Clopidogrel: <75 Years of Age
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.727
Comments p-value is for the 30 day comparison. ANCOVA Model: Measurement = treatment + baseline value + clopidogrel status at randomization.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric Ratio Estimate
Estimated Value 1.018
Confidence Interval (2-Sided) 95%
0.919 to 1.129
Estimation Comments Geometric Ratio Estimate is for the 30 day comparison.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Prasugrel: <75 Years of Age, Clopidogrel: <75 Years of Age
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.346
Comments p-value is for the 6 month comparison. ANCOVA Model: Measurement = treatment + baseline value + clopidogrel status at randomization.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric Ratio Estimate
Estimated Value 1.057
Confidence Interval (2-Sided) 95%
0.942 to 1.187
Estimation Comments Geometric Ratio Estimate is for the 6 month comparison.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Prasugrel: 75 Years of Age or Older, Clopidogrel: 75 Years of Age or Older
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.458
Comments p-value is for the 30 day comparison. ANCOVA Model: Measurement = treatment + baseline value + clopidogrel status at randomization.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric Ratio Estimate
Estimated Value 1.096
Confidence Interval (2-Sided) 95%
0.859 to 1.399
Estimation Comments Geometric Ratio Estimate is for the 30 day comparison.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Prasugrel: 75 Years of Age or Older, Clopidogrel: 75 Years of Age or Older
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.802
Comments p-value is for the 6 month comparison. ANCOVA Model: Measurement = treatment + baseline value + clopidogrel status at randomization.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric Ratio Estimate
Estimated Value 1.033
Confidence Interval (2-Sided) 95%
0.803 to 1.329
Estimation Comments Geometric Ratio Estimate is for the 6 month comparison.
8.Secondary Outcome
Title Genotyping Related to Drug Metabolism
Hide Description Variation in the genes encoding the cytochrome P450 (CYP) enzymes (CYP2C19) can reduce the ability to metabolize clopidogrel and a reduced platelet response and have been associated with increased rates of CV events including CV death. Participants were classified as extensive metabolizers (EM); reduced metabolizers (RM); or unknown (UNK) metabolizers based on their CYP2C19 genotype. Possible extensive metabolizer (EM) phenotypes include EM=extensive metabolizer, UM=ultra-rapid metabolizer, and EM (non-UM) that are not UM. Possible reduced metabolizer (RM) phenotypes include IM=intermediate metabolizer and PM=poor metabolizer. Genotypes associated with each predicted phenotype are presented; predicted phenotype is presented first followed by the genotype. Percentage=(number of participants with the predicted phenotype and genotype divided by the total number of participants per arm) multiplied by 100.
Time Frame Baseline
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who provided a DNA sample.
Arm/Group Title Prasugrel: <75 Years of Age Prasugrel: 75 Years of Age or Older Clopidogrel: <75 Years of Age Clopidogrel: 75 Years of Age or Older
Hide Arm/Group Description:
Prasugrel and Low-dose Commercially-available Aspirin in participants less than (<) 75 years of age. Commercially-available Aspirin: Low-dose aspirin, oral, as prescribed by physician through end of study Prasugrel: 30 milligram (mg), oral, once as loading dose (in those subjects who initiate study drug with a loading dose); and either 5 mg or 10 mg (based upon weight) orally, once daily as maintenance dose through end of study.
Prasugrel and Low-dose Commercially-available Aspirin in participants 75 years of age or older. Commercially-available Aspirin: Low-dose aspirin, oral, as prescribed by physician through end of study. Prasugrel: 30 milligram (mg), oral, once as loading dose (in those subjects who initiate study drug with a loading dose); and 5 mg orally, once daily as maintenance dose through end of study.
Clopidogrel and Low-Dose Commercially-available Aspirin in participants less than (<) 75 years of age. Commercially-available Aspirin: Low-dose aspirin, oral, as prescribed by physician through end of study. Clopidogrel: 300 milligram (mg), oral, once as loading dose (in those subjects who initiate study drug with a loading dose); and 75 mg, oral, once daily as maintenance dose through end of study.
Clopidogrel and Low-Dose Commercially-available Aspirin in participants 75 years of age or older. Commercially-available Aspirin: Low-dose aspirin, oral, as prescribed by physician through end of study. Clopidogrel: 300 milligram (mg), oral, once as loading dose (in those subjects who initiate study drug with a loading dose); and 75 mg, oral, once daily as maintenance dose through end of study.
Overall Number of Participants Analyzed 2210 639 2237 650
Measure Type: Number
Unit of Measure: percentage participants with geneotype
UM, *1/*17 24.0 25.0 25.1 21.8
UM, *17/*17 5.1 3.6 5.4 4.3
EM (non-UM), *1/*1 38.8 42.1 35.7 41.2
IM, *1/*2 18.6 18.3 19.8 19.7
IM, *1/*3 0.8 0.6 0.5 0.6
IM, *1/*4 0.4 0.0 0.1 0.3
IM, *1/*6 0.0 0.2 0.0 0.2
IM, *1/*8 0.1 0.5 0.4 0.3
PM, *2/*2 3.9 2.2 4.3 3.8
PM, *2/*3 0.3 0.2 0.3 0.3
PM, *2/*4 0.0 0.2 0.2 0.2
PM, *2/*6 0.0 0.0 0.0 0.0
PM, *2/*8 0.0 0.0 0.0 0.0
PM, *3/*3 0.0 0.0 0.2 0.0
UNK, *1/*10 0.0 0.0 0.1 0.0
UNK, *1/*13 0.0 0.2 0.0 0.0
UNK, *1/*9 0.1 0.2 0.0 0.0
UNK, *1/*9, *9/*17 0.0 0.0 0.0 0.0
UNK, *13/*17 0.0 0.0 0.0 0.0
UNK, *2/*13 0.0 0.0 0.0 0.0
UNK, *2/*17 6.3 6.1 6.8 6.2
UNK, *2/*9 0.0 0.0 0.1 0.0
UNK, *3/*17 0.1 0.0 0.0 0.3
UNK, *4/*17 0.2 0.2 0.2 0.0
UNK, *4/*9 0.0 0.0 0.0 0.0
UNK, *6/*17 0.0 0.0 0.0 0.2
UNK, *8/*17 0.2 0.0 0.1 0.0
UNK, *9/*17 0.0 0.0 0.0 0.0
UNK, Undefined genotype 0.7 0.6 0.5 0.6
9.Secondary Outcome
Title Economic and Quality of Life Outcomes
Hide Description Seattle Angina Questionnaire (SAQ) is a validated, disease-specific questionnaire containing 11 questions (Q) yielding 5 summary scales related to angina: physical limitations, angina stability, angina frequency, treatment satisfaction and disease perception. In this study only angina frequency and the physical limitations scales were assessed. Anginal Frequency was assessed using Q3 and Q4 which consists of a Likert scale ranging from 1 to 6 (higher values equals better quality of life) to assess how often a patient is having symptoms now. Physical limitations was assessed using Q1 which contains 9 items each assessed via Likert scale ranging from 1 to 6 (higher values equals better quality of life) to assess how much a participant's condition is hampering their ability to do what they want to do. Scale scores are transformed to a 0-100 by subtracting the lowest possible score, dividing by the range of the scale, and multiplying by 100. Higher values equal better quality of life.
Time Frame Baseline and follow-up (24 months)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants (combined <75 years and 75 years and older) with SAQ data.
Arm/Group Title Prasugrel Clopidogrel
Hide Arm/Group Description:
Prasugrel and Low-dose Commercially-available Aspirin in participants. Commercially-available Aspirin: Low-dose aspirin, oral, as prescribed by physician through end of study Prasugrel: 30 milligram (mg), oral, once as loading dose (in those subjects who initiate study drug with a loading dose); and either 5 mg or 10 mg (based upon weight and age), oral, once daily as maintenance dose through end of study.
Clopidogrel and Low-Dose Commercially-available Aspirin in participants. Commercially-available Aspirin: Low-dose aspirin, oral, as prescribed by physician through end of study. Clopidogrel: 300 milligram (mg), oral, once as loading dose (in those subjects who initiate study drug with a loading dose); and 75 mg, oral, once daily as maintenance dose through end of study.
Overall Number of Participants Analyzed 1506 1506
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline, physical limitations 67.8  (26.1) 67.0  (26.5)
Baseline, angina frequency 73.6  (22.9) 73.1  (23.5)
24 Months, physical limitations (n=420, 412) 75.1  (24.4) 74.5  (25.7)
24 Months, angina frequency (n=420, 412) 89.7  (20.0) 89.5  (19.1)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Prasugrel, Clopidogrel
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5
Comments p-value is for the comparison of physical limitations at baseline. p-values are from a regression model with treatment group and the respective baseline quality-of-life measure as predictors.
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Prasugrel, Clopidogrel
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.72
Comments p-value is for the comparison of angina frequency at baseline. p-values are from a regression model with treatment group and the respective baseline quality-of-life measure as predictors.
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Prasugrel, Clopidogrel
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.63
Comments p-value is for the comparison of physical limitations at 24 months. p-values are from a regression model with treatment group and the respective baseline quality-of-life measure as predictors.
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Prasugrel, Clopidogrel
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.53
Comments p-value is for the comparison of angina frequency at at 24 months. p-values are from a regression model with treatment group and the respective baseline quality-of-life measure as predictors.
Method ANCOVA
Comments [Not Specified]
10.Secondary Outcome
Title Summary of All Deaths
Hide Description All deaths, regardless of possible relatedness, with the exception of 1 event, were adjudicated by the Clinical Endpoint Committee (CEC) and are reported in this table. The 1 event which was not adjudicated was a result of the revocation of consent by the participant prior to their death. Deaths possibly related to study drug in the opinion of the investigator are also contained in the Serious Adverse Event (SAE) module.
Time Frame Randomization through end of study (30-month visit)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants
Arm/Group Title Prasugrel: <75 Years of Age Prasugrel: 75 Years of Age or Older Clopidogrel: <75 Years of Age Clopidogrel: 75 Years of Age or Older
Hide Arm/Group Description:

Prasugrel and Low-dose Commercially-available Aspirin in participants less than (<) 75 years of age.

Commercially-available Aspirin: Low-dose aspirin, oral, as prescribed by physician through end of study.

Prasugrel: 30 milligram (mg), oral, once as loading dose (in those subjects who initiate study drug with a loading dose); and either 5 mg or 10 mg (based upon weight) orally, once daily as maintenance dose through end of study.

Prasugrel and Low-dose Commercially-available Aspirin in participants 75 years of age or older.

Commercially-available Aspirin: Low-dose aspirin, oral, as prescribed by physician through end of study.

Prasugrel: 30 milligram (mg), oral, once as loading dose (in those subjects who initiate study drug with a loading dose); and either 5 mg orally, once daily as maintenance dose through end of study.

Clopidogrel and Low-Dose Commercially-available Aspirin in participants less than (<) 75 years of age.

Commercially-available Aspirin : Low-dose aspirin, oral, as prescribed by physician through end of study

Clopidogrel : 300 milligram (mg), oral, once as loading dose (in those subjects who initiate study drug with a loading dose); and 75 mg, oral, once daily as maintenance dose through end of study

Clopidogrel and Low-Dose Commercially-available Aspirin in participants 75 years of age or older.

Commercially-available Aspirin: Low-dose aspirin, oral, as prescribed by physician through end of study.

Clopidogrel: 300 milligram (mg), oral, once as loading dose (in those subjects who initiate study drug with a loading dose); and 75 mg, oral, once daily as maintenance dose through end of study.

Overall Number of Participants Analyzed 3620 1043 3623 1040
Measure Type: Number
Unit of Measure: participants
Congestive Heart Failure 10 21 13 23
Cardiogenic Shock 8 4 10 9
Cardiac Rupture 0 1 0 0
Myocardial Infarction 16 24 24 21
Dysrhythmia 5 2 6 3
Stent Thrombosis 0 0 0 0
Directly Related to Revascularization-CABG or PCI 1 1 1 1
Intracranial Hemorrhage 2 1 4 1
Non-Hemorrhagic Stroke 4 4 4 3
Sudden death due to cardiovascular event 75 39 70 43
Pulmonary Embolism 0 1 2 1
Stroke, unknown type 0 1 0 0
Other Cardiovascular Event 6 1 0 1
Cardiovascular event, unknown type 40 41 45 45
Accidental 1 0 1 1
Trauma 2 3 0 1
Hemorrhage, not intracranial 1 1 0 4
Infection 14 21 16 17
Malignancy 14 7 14 11
Suicide 1 0 0 0
Other Non-Cardiovascular event 8 4 8 6
Cause unknown (nonadjudicated event) 0 1 0 0
Time Frame [Not Specified]
Adverse Event Reporting Description Events leading to death, MI, stroke, stent thrombosis, or rehospitalization for recurrent UA were not recorded as an SAEs unless the event was possibly due to study drug.
 
Arm/Group Title Prasugrel Clopidogrel
Hide Arm/Group Description Prasugrel and Low-dose Commercially-available Aspirin in participants. Commercially-available Aspirin: Low-dose aspirin, oral, as prescribed by physician through end of study Prasugrel: 30 milligram (mg), oral, once as loading dose (in those subjects who initiate study drug with a loading dose); and either 5 mg or 10 mg (based upon weight and age), oral, once daily as maintenance dose through end of study. Clopidogrel and Low-Dose Commercially-available Aspirin in participants. Commercially-available Aspirin: Low-dose aspirin, oral, as prescribed by physician through end of study. Clopidogrel: 300 milligram (mg), oral, once as loading dose (in those subjects who initiate study drug with a loading dose); and 75 mg, oral, once daily as maintenance dose through end of study.
All-Cause Mortality
Prasugrel Clopidogrel
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Prasugrel Clopidogrel
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1573/4623 (34.03%)      1594/4617 (34.52%)    
Blood and lymphatic system disorders     
Anaemia  1  23/4623 (0.50%)  23 23/4617 (0.50%)  23
Anaemia haemolytic autoimmune  1  1/4623 (0.02%)  1 0/4617 (0.00%)  0
Autoimmune thrombocytopenia  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Bicytopenia  1  1/4623 (0.02%)  1 0/4617 (0.00%)  0
Coagulopathy  1  0/4623 (0.00%)  0 2/4617 (0.04%)  2
Haemorrhagic anaemia  1  1/4623 (0.02%)  1 0/4617 (0.00%)  0
Hypochromic anaemia  1  1/4623 (0.02%)  1 0/4617 (0.00%)  0
Iron deficiency anaemia  1  3/4623 (0.06%)  3 5/4617 (0.11%)  5
Microcytic anaemia  1  1/4623 (0.02%)  1 1/4617 (0.02%)  1
Normochromic normocytic anaemia  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Pancytopenia  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Red blood cell abnormality  1  1/4623 (0.02%)  1 0/4617 (0.00%)  0
Splenic infarction  1  1/4623 (0.02%)  1 1/4617 (0.02%)  1
Thrombocytopenia  1  1/4623 (0.02%)  1 1/4617 (0.02%)  1
Cardiac disorders     
Acute coronary syndrome  1  17/4623 (0.37%)  17 19/4617 (0.41%)  24
Acute left ventricular failure  1  8/4623 (0.17%)  11 9/4617 (0.19%)  10
Acute myocardial infarction  1  194/4623 (4.20%)  241 194/4617 (4.20%)  244
Angina pectoris  1  115/4623 (2.49%)  125 129/4617 (2.79%)  139
Angina unstable  1  290/4623 (6.27%)  351 310/4617 (6.71%)  374
Aortic valve disease  1  1/4623 (0.02%)  1 1/4617 (0.02%)  1
Aortic valve incompetence  1  2/4623 (0.04%)  2 2/4617 (0.04%)  2
Aortic valve stenosis  1  2/4623 (0.04%)  2 1/4617 (0.02%)  1
Arrhythmia  1  7/4623 (0.15%)  7 2/4617 (0.04%)  2
Arrhythmia supraventricular  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Arteriosclerosis coronary artery  1  4/4623 (0.09%)  4 4/4617 (0.09%)  4
Arteriospasm coronary  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Atrial fibrillation  1  82/4623 (1.77%)  88 69/4617 (1.49%)  71
Atrial flutter  1  12/4623 (0.26%)  12 4/4617 (0.09%)  5
Atrial tachycardia  1  2/4623 (0.04%)  2 3/4617 (0.06%)  3
Atrial thrombosis  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Atrioventricular block  1  3/4623 (0.06%)  3 6/4617 (0.13%)  7
Atrioventricular block complete  1  2/4623 (0.04%)  2 5/4617 (0.11%)  5
Atrioventricular block second degree  1  0/4623 (0.00%)  0 2/4617 (0.04%)  2
Bradyarrhythmia  1  1/4623 (0.02%)  1 1/4617 (0.02%)  1
Bradycardia  1  7/4623 (0.15%)  8 14/4617 (0.30%)  14
Bundle branch block left  1  1/4623 (0.02%)  1 0/4617 (0.00%)  0
Bundle branch block right  1  1/4623 (0.02%)  1 0/4617 (0.00%)  0
Cardiac arrest  1  29/4623 (0.63%)  30 28/4617 (0.61%)  28
Cardiac disorder  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Cardiac failure  1  68/4623 (1.47%)  75 67/4617 (1.45%)  81
Cardiac failure acute  1  12/4623 (0.26%)  12 19/4617 (0.41%)  19
Cardiac failure chronic  1  36/4623 (0.78%)  36 41/4617 (0.89%)  41
Cardiac failure congestive  1  83/4623 (1.80%)  96 104/4617 (2.25%)  111
Cardiac flutter  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Cardiac tamponade  1  1/4623 (0.02%)  1 0/4617 (0.00%)  0
Cardiac valve disease  1  1/4623 (0.02%)  1 0/4617 (0.00%)  0
Cardio-respiratory arrest  1  8/4623 (0.17%)  8 14/4617 (0.30%)  14
Cardiogenic shock  1  15/4623 (0.32%)  15 23/4617 (0.50%)  23
Cardiomegaly  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Cardiomyopathy  1  3/4623 (0.06%)  3 1/4617 (0.02%)  1
Cardiopulmonary failure  1  5/4623 (0.11%)  5 3/4617 (0.06%)  3
Cardiovascular insufficiency  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Congestive cardiomyopathy  1  2/4623 (0.04%)  2 1/4617 (0.02%)  2
Cor pulmonale  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Coronary artery disease  1  43/4623 (0.93%)  43 39/4617 (0.84%)  39
Coronary artery dissection  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Coronary artery occlusion  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Coronary artery perforation  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Coronary artery stenosis  1  8/4623 (0.17%)  8 7/4617 (0.15%)  7
Coronary artery thrombosis  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Diastolic dysfunction  1  1/4623 (0.02%)  1 0/4617 (0.00%)  0
Ischaemic cardiomyopathy  1  4/4623 (0.09%)  4 3/4617 (0.06%)  3
Left ventricular dysfunction  1  1/4623 (0.02%)  1 2/4617 (0.04%)  2
Left ventricular failure  1  4/4623 (0.09%)  4 8/4617 (0.17%)  8
Low cardiac output syndrome  1  1/4623 (0.02%)  1 0/4617 (0.00%)  0
Mitral valve disease  1  1/4623 (0.02%)  1 1/4617 (0.02%)  1
Mitral valve incompetence  1  2/4623 (0.04%)  2 1/4617 (0.02%)  1
Myocardial fibrosis  1  1/4623 (0.02%)  1 0/4617 (0.00%)  0
Myocardial infarction  1  142/4623 (3.07%)  166 143/4617 (3.10%)  166
Myocardial ischaemia  1  31/4623 (0.67%)  31 41/4617 (0.89%)  41
Palpitations  1  2/4623 (0.04%)  2 3/4617 (0.06%)  3
Pericardial effusion  1  2/4623 (0.04%)  2 0/4617 (0.00%)  0
Pericarditis  1  2/4623 (0.04%)  2 0/4617 (0.00%)  0
Postinfarction angina  1  5/4623 (0.11%)  5 4/4617 (0.09%)  4
Prinzmetal angina  1  2/4623 (0.04%)  2 0/4617 (0.00%)  0
Sick sinus syndrome  1  1/4623 (0.02%)  1 3/4617 (0.06%)  3
Sinus arrest  1  1/4623 (0.02%)  1 0/4617 (0.00%)  0
Sinus bradycardia  1  2/4623 (0.04%)  2 1/4617 (0.02%)  1
Stress cardiomyopathy  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Supraventricular tachycardia  1  4/4623 (0.09%)  4 8/4617 (0.17%)  8
Tachycardia  1  1/4623 (0.02%)  1 3/4617 (0.06%)  3
Ventricle rupture  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Ventricular arrhythmia  1  4/4623 (0.09%)  4 0/4617 (0.00%)  0
Ventricular extrasystoles  1  2/4623 (0.04%)  2 5/4617 (0.11%)  5
Ventricular fibrillation  1  3/4623 (0.06%)  3 15/4617 (0.32%)  17
Ventricular tachycardia  1  15/4623 (0.32%)  17 20/4617 (0.43%)  23
Congenital, familial and genetic disorders     
Branchial cyst  1  1/4623 (0.02%)  1 0/4617 (0.00%)  0
Gastrointestinal angiodysplasia  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Glucose-6-phosphate dehydrogenase deficiency  1  1/4623 (0.02%)  1 0/4617 (0.00%)  0
Hydrocele  1  1/4623 (0.02%)  1 0/4617 (0.00%)  0
Phimosis  1  1/4623 (0.02%)  1 0/4617 (0.00%)  0
Ear and labyrinth disorders     
Deafness unilateral  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Vertigo  1  5/4623 (0.11%)  5 4/4617 (0.09%)  4
Vertigo positional  1  1/4623 (0.02%)  1 2/4617 (0.04%)  2
Endocrine disorders     
Goitre  1  1/4623 (0.02%)  1 1/4617 (0.02%)  1
Hyperthyroidism  1  1/4623 (0.02%)  1 0/4617 (0.00%)  0
Primary hyperaldosteronism  1  1/4623 (0.02%)  1 0/4617 (0.00%)  0
Primary hypothyroidism  1  1/4623 (0.02%)  1 0/4617 (0.00%)  0
Eye disorders     
Amaurosis  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Cataract  1  8/4623 (0.17%)  9 4/4617 (0.09%)  5
Conjunctival haemorrhage  1  1/4623 (0.02%)  1 1/4617 (0.02%)  1
Corneal oedema  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Diabetic retinopathy  1  0/4623 (0.00%)  0 1/4617 (0.02%)  2
Diplopia  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Eye haemorrhage  1  1/4623 (0.02%)  1 1/4617 (0.02%)  1
Glaucoma  1  0/4623 (0.00%)  0 2/4617 (0.04%)  2
Open angle glaucoma  1  1/4623 (0.02%)  1 0/4617 (0.00%)  0
Ophthalmoplegia  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Retinal artery occlusion  1  1/4623 (0.02%)  1 0/4617 (0.00%)  0
Retinal detachment  1  0/4623 (0.00%)  0 2/4617 (0.04%)  3
Retinal haemorrhage  1  1/4623 (0.02%)  1 0/4617 (0.00%)  0
Retinal vein thrombosis  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Vision blurred  1  1/4623 (0.02%)  1 0/4617 (0.00%)  0
Vitreous haemorrhage  1  1/4623 (0.02%)  1 2/4617 (0.04%)  2
Gastrointestinal disorders     
Abdominal adhesions  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Abdominal hernia  1  2/4623 (0.04%)  2 2/4617 (0.04%)  2
Abdominal hernia obstructive  1  1/4623 (0.02%)  1 0/4617 (0.00%)  0
Abdominal pain  1  6/4623 (0.13%)  6 6/4617 (0.13%)  6
Abdominal pain lower  1  1/4623 (0.02%)  1 0/4617 (0.00%)  0
Abdominal pain upper  1  3/4623 (0.06%)  3 4/4617 (0.09%)  4
Abdominal wall haematoma  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Acute abdomen  1  2/4623 (0.04%)  2 0/4617 (0.00%)  0
Anal fissure  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Anal fistula  1  1/4623 (0.02%)  1 0/4617 (0.00%)  0
Ascites  1  1/4623 (0.02%)  1 0/4617 (0.00%)  0
Colitis  1  1/4623 (0.02%)  1 1/4617 (0.02%)  1
Colitis ischaemic  1  1/4623 (0.02%)  1 2/4617 (0.04%)  2
Colonic polyp  1  3/4623 (0.06%)  3 2/4617 (0.04%)  2
Constipation  1  2/4623 (0.04%)  2 3/4617 (0.06%)  3
Dental caries  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Diarrhoea  1  1/4623 (0.02%)  1 4/4617 (0.09%)  4
Diarrhoea haemorrhagic  1  1/4623 (0.02%)  1 0/4617 (0.00%)  0
Diverticulum  1  1/4623 (0.02%)  1 2/4617 (0.04%)  2
Diverticulum intestinal  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Diverticulum intestinal haemorrhagic  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Duodenal polyp  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Duodenal ulcer  1  6/4623 (0.13%)  6 4/4617 (0.09%)  4
Duodenal ulcer haemorrhage  1  4/4623 (0.09%)  4 2/4617 (0.04%)  2
Duodenitis  1  1/4623 (0.02%)  1 0/4617 (0.00%)  0
Dyspepsia  1  5/4623 (0.11%)  5 2/4617 (0.04%)  2
Dysphagia  1  3/4623 (0.06%)  3 4/4617 (0.09%)  4
Enteritis  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Epigastric discomfort  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Erosive duodenitis  1  2/4623 (0.04%)  2 0/4617 (0.00%)  0
Faecaloma  1  1/4623 (0.02%)  1 0/4617 (0.00%)  0
Femoral hernia  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Gastric disorder  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Gastric haemorrhage  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Gastric ulcer  1  3/4623 (0.06%)  3 1/4617 (0.02%)  1
Gastric ulcer haemorrhage  1  3/4623 (0.06%)  3 2/4617 (0.04%)  2
Gastric ulcer, obstructive  1  1/4623 (0.02%)  1 0/4617 (0.00%)  0
Gastritis  1  11/4623 (0.24%)  11 4/4617 (0.09%)  4
Gastritis erosive  1  2/4623 (0.04%)  2 3/4617 (0.06%)  3
Gastritis haemorrhagic  1  0/4623 (0.00%)  0 2/4617 (0.04%)  2
Gastrointestinal disorder  1  2/4623 (0.04%)  2 1/4617 (0.02%)  1
Gastrointestinal haemorrhage  1  39/4623 (0.84%)  39 22/4617 (0.48%)  22
Gastrointestinal inflammation  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Gastrointestinal pain  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Gastrointestinal ulcer haemorrhage  1  1/4623 (0.02%)  1 0/4617 (0.00%)  0
Gastrooesophageal reflux disease  1  6/4623 (0.13%)  6 3/4617 (0.06%)  3
Gingival bleeding  1  1/4623 (0.02%)  1 1/4617 (0.02%)  1
Haematemesis  1  6/4623 (0.13%)  6 0/4617 (0.00%)  0
Haematochezia  1  2/4623 (0.04%)  2 2/4617 (0.04%)  2
Haemorrhagic erosive gastritis  1  1/4623 (0.02%)  1 0/4617 (0.00%)  0
Haemorrhoidal haemorrhage  1  1/4623 (0.02%)  1 3/4617 (0.06%)  3
Haemorrhoids  1  1/4623 (0.02%)  1 0/4617 (0.00%)  0
Hiatus hernia  1  1/4623 (0.02%)  1 0/4617 (0.00%)  0
Ileus  1  1/4623 (0.02%)  1 1/4617 (0.02%)  1
Ileus paralytic  1  1/4623 (0.02%)  1 1/4617 (0.02%)  1
Impaired gastric emptying  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Inguinal hernia  1  2/4623 (0.04%)  3 6/4617 (0.13%)  6
Inguinal hernia strangulated  1  1/4623 (0.02%)  1 0/4617 (0.00%)  0
Inguinal hernia, obstructive  1  1/4623 (0.02%)  1 2/4617 (0.04%)  2
Intestinal angina  1  1/4623 (0.02%)  1 0/4617 (0.00%)  0
Intestinal fistula  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Intestinal haemorrhage  1  1/4623 (0.02%)  1 2/4617 (0.04%)  2
Intestinal ischaemia  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Intestinal mass  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Intestinal obstruction  1  1/4623 (0.02%)  1 3/4617 (0.06%)  3
Irritable bowel syndrome  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Localised intraabdominal fluid collection  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Lower gastrointestinal haemorrhage  1  8/4623 (0.17%)  8 3/4617 (0.06%)  3
Mallory-weiss syndrome  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Melaena  1  4/4623 (0.09%)  4 1/4617 (0.02%)  1
Mesenteric artery embolism  1  1/4623 (0.02%)  1 0/4617 (0.00%)  0
Nausea  1  1/4623 (0.02%)  1 2/4617 (0.04%)  2
Oesophageal ulcer  1  1/4623 (0.02%)  1 0/4617 (0.00%)  0
Oesophageal ulcer haemorrhage  1  1/4623 (0.02%)  1 0/4617 (0.00%)  0
Oesophagitis  1  1/4623 (0.02%)  1 1/4617 (0.02%)  1
Palatal oedema  1  1/4623 (0.02%)  1 0/4617 (0.00%)  0
Pancreatitis  1  1/4623 (0.02%)  1 5/4617 (0.11%)  6
Pancreatitis acute  1  2/4623 (0.04%)  2 5/4617 (0.11%)  5
Pancreatitis chronic  1  1/4623 (0.02%)  1 0/4617 (0.00%)  0
Pancreatitis haemorrhagic  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Pancreatitis relapsing  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Peptic ulcer  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Rectal haemorrhage  1  11/4623 (0.24%)  12 4/4617 (0.09%)  4
Retroperitoneal haemorrhage  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Sigmoiditis  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Small intestinal obstruction  1  3/4623 (0.06%)  5 3/4617 (0.06%)  4
Small intestinal perforation  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Subileus  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Umbilical hernia  1  1/4623 (0.02%)  1 1/4617 (0.02%)  1
Upper gastrointestinal haemorrhage  1  20/4623 (0.43%)  21 15/4617 (0.32%)  15
Varices oesophageal  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Vomiting  1  2/4623 (0.04%)  2 1/4617 (0.02%)  1
General disorders     
Adverse drug reaction  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Asthenia  1  8/4623 (0.17%)  8 3/4617 (0.06%)  3
Cardiac death  1  2/4623 (0.04%)  2 1/4617 (0.02%)  1
Chest discomfort  1  3/4623 (0.06%)  3 4/4617 (0.09%)  4
Chest pain  1  13/4623 (0.28%)  14 5/4617 (0.11%)  6
Chills  1  1/4623 (0.02%)  1 0/4617 (0.00%)  0
Death  1  34/4623 (0.74%)  34 40/4617 (0.87%)  40
Device malfunction  1  1/4623 (0.02%)  1 1/4617 (0.02%)  1
Euthanasia  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Generalised oedema  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Hernia  1  1/4623 (0.02%)  1 0/4617 (0.00%)  0
Impaired healing  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Malaise  1  2/4623 (0.04%)  2 0/4617 (0.00%)  0
Medical device complication  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Multi-organ failure  1  3/4623 (0.06%)  3 5/4617 (0.11%)  5
Necrosis  1  1/4623 (0.02%)  1 0/4617 (0.00%)  0
Non-cardiac chest pain  1  66/4623 (1.43%)  71 65/4617 (1.41%)  78
Oedema peripheral  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Pyrexia  1  3/4623 (0.06%)  3 3/4617 (0.06%)  3
Sudden cardiac death  1  12/4623 (0.26%)  12 16/4617 (0.35%)  16
Sudden death  1  45/4623 (0.97%)  45 46/4617 (1.00%)  46
Thrombosis in device  1  12/4623 (0.26%)  13 23/4617 (0.50%)  24
Ulcer haemorrhage  1  1/4623 (0.02%)  1 0/4617 (0.00%)  0
Hepatobiliary disorders     
Bile duct obstruction  1  1/4623 (0.02%)  1 0/4617 (0.00%)  0
Bile duct stone  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Biliary tract disorder  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Cholecystitis  1  6/4623 (0.13%)  6 4/4617 (0.09%)  4
Cholecystitis acute  1  9/4623 (0.19%)  10 8/4617 (0.17%)  9
Cholecystitis chronic  1  1/4623 (0.02%)  1 3/4617 (0.06%)  3
Cholelithiasis  1  4/4623 (0.09%)  4 10/4617 (0.22%)  10
Cholestasis  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Hepatic cirrhosis  1  4/4623 (0.09%)  4 0/4617 (0.00%)  0
Hepatic failure  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Hepatitis  1  0/4623 (0.00%)  0 2/4617 (0.04%)  2
Hyperplastic cholecystopathy  1  1/4623 (0.02%)  1 0/4617 (0.00%)  0
Portal vein thrombosis  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Immune system disorders     
Atopy  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Drug hypersensitivity  1  1/4623 (0.02%)  1 1/4617 (0.02%)  1
Hypersensitivity  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Immunosuppression  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Kidney transplant rejection  1  0/4623 (0.00%)  0 1/4617 (0.02%)  2
Infections and infestations     
Abdominal abscess  1  1/4623 (0.02%)  1 0/4617 (0.00%)  0
Abdominal sepsis  1  1/4623 (0.02%)  1 1/4617 (0.02%)  1
Abdominal wall abscess  1  1/4623 (0.02%)  1 0/4617 (0.00%)  0
Abscess limb  1  2/4623 (0.04%)  2 1/4617 (0.02%)  1
Abscess neck  1  0/4623 (0.00%)  0 1/4617 (0.02%)  2
Acute sinusitis  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Anal abscess  1  1/4623 (0.02%)  1 2/4617 (0.04%)  2
Appendiceal abscess  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Appendicitis  1  1/4623 (0.02%)  1 3/4617 (0.06%)  3
Appendicitis perforated  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Bacteraemia  1  1/4623 (0.02%)  1 0/4617 (0.00%)  0
Bronchitis  1  11/4623 (0.24%)  12 15/4617 (0.32%)  15
Bronchitis bacterial  1  0/4623 (0.00%)  0 2/4617 (0.04%)  2
Bronchopneumonia  1  8/4623 (0.17%)  8 8/4617 (0.17%)  10
Bronchopulmonary aspergillosis  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Burkholderia cepacia complex infection  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Burkholderia pseudomallei infection  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Cellulitis  1  9/4623 (0.19%)  9 11/4617 (0.24%)  12
Cholecystitis infective  1  1/4623 (0.02%)  1 0/4617 (0.00%)  0
Cystitis  1  1/4623 (0.02%)  1 1/4617 (0.02%)  1
Cytomegalovirus colitis  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Device related infection  1  2/4623 (0.04%)  2 0/4617 (0.00%)  0
Diabetic gangrene  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Diarrhoea infectious  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Disseminated tuberculosis  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Diverticulitis  1  3/4623 (0.06%)  3 1/4617 (0.02%)  1
Ear infection  1  1/4623 (0.02%)  1 0/4617 (0.00%)  0
Eczema infected  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Enterocolitis bacterial  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Erysipelas  1  2/4623 (0.04%)  2 5/4617 (0.11%)  5
Escherichia urinary tract infection  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Fungal infection  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Furuncle  1  1/4623 (0.02%)  1 0/4617 (0.00%)  0
Gangrene  1  4/4623 (0.09%)  4 1/4617 (0.02%)  1
Gastroenteritis  1  7/4623 (0.15%)  7 7/4617 (0.15%)  7
Gastroenteritis norovirus  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Gastroenteritis viral  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Gastrointestinal viral infection  1  1/4623 (0.02%)  1 0/4617 (0.00%)  0
Groin abscess  1  1/4623 (0.02%)  1 0/4617 (0.00%)  0
Haematoma infection  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Helicobacter gastritis  1  1/4623 (0.02%)  1 0/4617 (0.00%)  0
Hepatitis b  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Hepatitis c  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Herpes zoster  1  2/4623 (0.04%)  2 0/4617 (0.00%)  0
Herpes zoster ophthalmic  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Infection  1  1/4623 (0.02%)  1 0/4617 (0.00%)  0
Infectious peritonitis  1  1/4623 (0.02%)  1 1/4617 (0.02%)  1
Infective exacerbation of chronic obstructive airways disease  1  1/4623 (0.02%)  1 0/4617 (0.00%)  0
Labyrinthitis  1  2/4623 (0.04%)  2 1/4617 (0.02%)  1
Lobar pneumonia  1  2/4623 (0.04%)  2 1/4617 (0.02%)  1
Localised infection  1  1/4623 (0.02%)  1 0/4617 (0.00%)  0
Lower respiratory tract infection  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Lower respiratory tract infection viral  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Lung abscess  1  1/4623 (0.02%)  1 0/4617 (0.00%)  0
Lung infection  1  0/4623 (0.00%)  0 2/4617 (0.04%)  2
Lymphangitis  1  1/4623 (0.02%)  1 0/4617 (0.00%)  0
Malaria  1  2/4623 (0.04%)  2 0/4617 (0.00%)  0
Mediastinitis  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Meningitis tuberculous  1  1/4623 (0.02%)  1 0/4617 (0.00%)  0
Muscle abscess  1  1/4623 (0.02%)  1 0/4617 (0.00%)  0
Onychomycosis  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Orchitis  1  1/4623 (0.02%)  1 0/4617 (0.00%)  0
Osteomyelitis  1  5/4623 (0.11%)  5 4/4617 (0.09%)  4
Osteomyelitis chronic  1  1/4623 (0.02%)  1 1/4617 (0.02%)  1
Parametritis  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Paronychia  1  1/4623 (0.02%)  1 0/4617 (0.00%)  0
Peridiverticular abscess  1  2/4623 (0.04%)  2 0/4617 (0.00%)  0
Perirectal abscess  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Pneumonia  1  74/4623 (1.60%)  86 76/4617 (1.65%)  79
Pneumonia bacterial  1  2/4623 (0.04%)  2 0/4617 (0.00%)  0
Pneumonia haemophilus  1  1/4623 (0.02%)  1 0/4617 (0.00%)  0
Pneumonia mycoplasmal  1  1/4623 (0.02%)  1 0/4617 (0.00%)  0
Pneumonia staphylococcal  1  1/4623 (0.02%)  1 1/4617 (0.02%)  1
Pneumonia viral  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Post procedural infection  1  1/4623 (0.02%)  1 0/4617 (0.00%)  0
Postoperative wound infection  1  2/4623 (0.04%)  2 1/4617 (0.02%)  1
Pulmonary tuberculosis  1  1/4623 (0.02%)  1 1/4617 (0.02%)  1
Pyelonephritis  1  1/4623 (0.02%)  1 2/4617 (0.04%)  2
Pyelonephritis acute  1  2/4623 (0.04%)  2 2/4617 (0.04%)  2
Pyelonephritis chronic  1  1/4623 (0.02%)  1 0/4617 (0.00%)  0
Pyonephrosis  1  1/4623 (0.02%)  1 0/4617 (0.00%)  0
Rectal abscess  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Renal abscess  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Respiratory tract infection  1  3/4623 (0.06%)  3 7/4617 (0.15%)  7
Salmonellosis  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Scrotal abscess  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Sepsis  1  11/4623 (0.24%)  11 12/4617 (0.26%)  12
Septic shock  1  6/4623 (0.13%)  6 8/4617 (0.17%)  8
Sinusitis  1  1/4623 (0.02%)  1 0/4617 (0.00%)  0
Skin infection  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Staphylococcal bacteraemia  1  1/4623 (0.02%)  1 1/4617 (0.02%)  1
Staphylococcal infection  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Staphylococcal sepsis  1  1/4623 (0.02%)  1 0/4617 (0.00%)  0
Subcutaneous abscess  1  2/4623 (0.04%)  2 0/4617 (0.00%)  0
Tracheobronchitis  1  2/4623 (0.04%)  2 2/4617 (0.04%)  2
Tuberculosis  1  1/4623 (0.02%)  1 0/4617 (0.00%)  0
Upper respiratory tract infection  1  2/4623 (0.04%)  2 2/4617 (0.04%)  2
Urinary tract infection  1  33/4623 (0.71%)  34 19/4617 (0.41%)  20
Urosepsis  1  4/4623 (0.09%)  4 3/4617 (0.06%)  3
Viral diarrhoea  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Viral infection  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Viral upper respiratory tract infection  1  1/4623 (0.02%)  1 0/4617 (0.00%)  0
Wound infection  1  1/4623 (0.02%)  1 2/4617 (0.04%)  2
Injury, poisoning and procedural complications     
Accidental overdose  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Alcohol poisoning  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Ankle fracture  1  2/4623 (0.04%)  2 4/4617 (0.09%)  4
Arteriovenous fistula site haemorrhage  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Brain contusion  1  1/4623 (0.02%)  1 0/4617 (0.00%)  0
Chemical burns of eye  1  1/4623 (0.02%)  1 0/4617 (0.00%)  0
Concussion  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Confusion postoperative  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Contusion  1  1/4623 (0.02%)  1 3/4617 (0.06%)  3
Coronary artery restenosis  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Face injury  1  1/4623 (0.02%)  1 0/4617 (0.00%)  0
Facial bones fracture  1  1/4623 (0.02%)  1 0/4617 (0.00%)  0
Fall  1  5/4623 (0.11%)  5 1/4617 (0.02%)  1
Femoral neck fracture  1  1/4623 (0.02%)  1 3/4617 (0.06%)  3
Femur fracture  1  7/4623 (0.15%)  7 7/4617 (0.15%)  7
Fibula fracture  1  0/4623 (0.00%)  0 2/4617 (0.04%)  2
Foot fracture  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Gun shot wound  1  1/4623 (0.02%)  1 2/4617 (0.04%)  2
Haematuria traumatic  1  1/4623 (0.02%)  1 0/4617 (0.00%)  0
Hand fracture  1  2/4623 (0.04%)  2 1/4617 (0.02%)  1
Head injury  1  2/4623 (0.04%)  2 1/4617 (0.02%)  1
Hip fracture  1  6/4623 (0.13%)  6 6/4617 (0.13%)  6
Humerus fracture  1  1/4623 (0.02%)  1 1/4617 (0.02%)  1
In-stent coronary artery restenosis  1  3/4623 (0.06%)  3 7/4617 (0.15%)  7
Incisional hernia, obstructive  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Joint dislocation  1  1/4623 (0.02%)  1 1/4617 (0.02%)  1
Limb injury  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Lower limb fracture  1  1/4623 (0.02%)  1 0/4617 (0.00%)  0
Lumbar vertebral fracture  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Multiple drug overdose  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Muscle rupture  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Operative haemorrhage  1  0/4623 (0.00%)  0 2/4617 (0.04%)  2
Overdose  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Pelvic fracture  1  1/4623 (0.02%)  1 1/4617 (0.02%)  1
Periorbital haematoma  1  1/4623 (0.02%)  1 0/4617 (0.00%)  0
Periorbital haemorrhage  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Poisoning  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Post procedural haematoma  1  1/4623 (0.02%)  1 0/4617 (0.00%)  0
Post procedural haemorrhage  1  5/4623 (0.11%)  5 4/4617 (0.09%)  4
Post procedural myocardial infarction  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Postoperative fever  1  1/4623 (0.02%)  1 0/4617 (0.00%)  0
Postoperative thrombosis  1  1/4623 (0.02%)  1 0/4617 (0.00%)  0
Postoperative wound complication  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Pubis fracture  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Rib fracture  1  3/4623 (0.06%)  3 2/4617 (0.04%)  2
Road traffic accident  1  4/4623 (0.09%)  4 1/4617 (0.02%)  1
Scapula fracture  1  1/4623 (0.02%)  1 0/4617 (0.00%)  0
Skeletal injury  1  1/4623 (0.02%)  1 0/4617 (0.00%)  0
Skull fractured base  1  1/4623 (0.02%)  1 0/4617 (0.00%)  0
Soft tissue injury  1  1/4623 (0.02%)  1 0/4617 (0.00%)  0
Spinal column injury  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Spinal compression fracture  1  0/4623 (0.00%)  0 2/4617 (0.04%)  2
Spinal fracture  1  1/4623 (0.02%)  1 0/4617 (0.00%)  0
Splenic rupture  1  0/4623 (0.00%)  0 2/4617 (0.04%)  2
Stab wound  1  1/4623 (0.02%)  1 0/4617 (0.00%)  0
Sternal fracture  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Subcutaneous haematoma  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Subdural haematoma  1  7/4623 (0.15%)  8 7/4617 (0.15%)  7
Subdural haemorrhage  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Tendon rupture  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Thermal burn  1  1/4623 (0.02%)  1 3/4617 (0.06%)  3
Tibia fracture  1  1/4623 (0.02%)  1 2/4617 (0.04%)  2
Tooth fracture  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Toxicity to various agents  1  1/4623 (0.02%)  1 0/4617 (0.00%)  0
Traumatic haematoma  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Traumatic intracranial haemorrhage  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Vascular graft occlusion  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Vascular pseudoaneurysm  1  3/4623 (0.06%)  3 2/4617 (0.04%)  2
Weaning failure  1  1/4623 (0.02%)  1 0/4617 (0.00%)  0
Wound  1  2/4623 (0.04%)  2 0/4617 (0.00%)  0
Wound dehiscence  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Wound haemorrhage  1  1/4623 (0.02%)  1 0/4617 (0.00%)  0
Wound secretion  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Investigations     
Acinetobacter test positive  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Alanine aminotransferase increased  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Angiogram  1  1/4623 (0.02%)  1 0/4617 (0.00%)  0
Aspartate aminotransferase increased  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Blood glucose fluctuation  1  1/4623 (0.02%)  1 0/4617 (0.00%)  0
Blood glucose increased  1  2/4623 (0.04%)  2 0/4617 (0.00%)  0
Blood pressure increased  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Catheterisation cardiac  1  1/4623 (0.02%)  1 0/4617 (0.00%)  0
Coagulation time prolonged  1  1/4623 (0.02%)  1 0/4617 (0.00%)  0
Ejection fraction decreased  1  1/4623 (0.02%)  1 0/4617 (0.00%)  0
Electrocardiogram qt prolonged  1  1/4623 (0.02%)  1 0/4617 (0.00%)  0
Electrocardiogram st segment elevation  1  1/4623 (0.02%)  1 0/4617 (0.00%)  0
Haematocrit decreased  1  1/4623 (0.02%)  1 0/4617 (0.00%)  0
Haemoglobin decreased  1  2/4623 (0.04%)  2 1/4617 (0.02%)  1
Hepatic enzyme increased  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Occult blood  1  1/4623 (0.02%)  1 1/4617 (0.02%)  1
Prostatic specific antigen increased  1  1/4623 (0.02%)  1 0/4617 (0.00%)  0
Metabolism and nutrition disorders     
Acidosis  1  1/4623 (0.02%)  1 0/4617 (0.00%)  0
Cachexia  1  1/4623 (0.02%)  1 0/4617 (0.00%)  0
Dehydration  1  4/4623 (0.09%)  4 5/4617 (0.11%)  5
Diabetes mellitus  1  13/4623 (0.28%)  13 9/4617 (0.19%)  9
Diabetes mellitus inadequate control  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Diabetic foot  1  5/4623 (0.11%)  5 3/4617 (0.06%)  3
Diabetic ketoacidosis  1  3/4623 (0.06%)  4 5/4617 (0.11%)  5
Electrolyte imbalance  1  1/4623 (0.02%)  1 0/4617 (0.00%)  0
Failure to thrive  1  1/4623 (0.02%)  1 1/4617 (0.02%)  1
Fluid overload  1  2/4623 (0.04%)  2 0/4617 (0.00%)  0
Gout  1  1/4623 (0.02%)  1 1/4617 (0.02%)  1
Hyperglycaemia  1  6/4623 (0.13%)  7 5/4617 (0.11%)  6
Hyperkalaemia  1  3/4623 (0.06%)  3 8/4617 (0.17%)  8
Hypoglycaemia  1  10/4623 (0.22%)  11 13/4617 (0.28%)  14
Hypokalaemia  1  1/4623 (0.02%)  1 3/4617 (0.06%)  3
Hyponatraemia  1  6/4623 (0.13%)  6 4/4617 (0.09%)  4
Hypovolaemia  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Metabolic acidosis  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Obesity  1  1/4623 (0.02%)  1 0/4617 (0.00%)  0
Shock hypoglycaemic  1  1/4623 (0.02%)  1 1/4617 (0.02%)  1
Type 2 diabetes mellitus  1  0/4623 (0.00%)  0 2/4617 (0.04%)  2
Musculoskeletal and connective tissue disorders     
Arthralgia  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Arthritis  1  0/4623 (0.00%)  0 2/4617 (0.04%)  2
Back pain  1  5/4623 (0.11%)  5 5/4617 (0.11%)  5
Bursitis  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Cervical spinal stenosis  1  1/4623 (0.02%)  1 1/4617 (0.02%)  1
Costochondritis  1  2/4623 (0.04%)  2 4/4617 (0.09%)  4
Dupuytren's contracture  1  1/4623 (0.02%)  1 0/4617 (0.00%)  0
Gouty arthritis  1  1/4623 (0.02%)  1 2/4617 (0.04%)  2
Haemarthrosis  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Intervertebral disc degeneration  1  1/4623 (0.02%)  1 0/4617 (0.00%)  0
Intervertebral disc disorder  1  2/4623 (0.04%)  2 0/4617 (0.00%)  0
Intervertebral disc protrusion  1  5/4623 (0.11%)  5 2/4617 (0.04%)  3
Joint effusion  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Musculoskeletal chest pain  1  5/4623 (0.11%)  5 5/4617 (0.11%)  5
Musculoskeletal pain  1  5/4623 (0.11%)  5 1/4617 (0.02%)  1
Myalgia  1  1/4623 (0.02%)  1 0/4617 (0.00%)  0
Myopathy  1  1/4623 (0.02%)  1 0/4617 (0.00%)  0
Osteoarthritis  1  6/4623 (0.13%)  6 11/4617 (0.24%)  11
Osteochondritis  1  1/4623 (0.02%)  1 1/4617 (0.02%)  1
Osteoporosis  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Pain in extremity  1  1/4623 (0.02%)  1 1/4617 (0.02%)  1
Periarthritis  1  1/4623 (0.02%)  1 0/4617 (0.00%)  0
Psoriatic arthropathy  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Rhabdomyolysis  1  1/4623 (0.02%)  1 2/4617 (0.04%)  2
Rheumatoid arthritis  1  2/4623 (0.04%)  2 1/4617 (0.02%)  1
Spinal column stenosis  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Spinal osteoarthritis  1  1/4623 (0.02%)  1 4/4617 (0.09%)  4
Spondylitis  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Synovial cyst  1  1/4623 (0.02%)  1 0/4617 (0.00%)  0
Synovitis  1  1/4623 (0.02%)  1 0/4617 (0.00%)  0
Tenosynovitis  1  1/4623 (0.02%)  1 0/4617 (0.00%)  0
Vertebral foraminal stenosis  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Benign laryngeal neoplasm  1  1/4623 (0.02%)  1 0/4617 (0.00%)  0
Benign ovarian tumour  1  1/4623 (0.02%)  1 0/4617 (0.00%)  0
Benign renal neoplasm  1  1/4623 (0.02%)  1 0/4617 (0.00%)  0
Benign small intestinal neoplasm  1  1/4623 (0.02%)  1 0/4617 (0.00%)  0
Colon adenoma  1  0/4623 (0.00%)  0 1/4617 (0.02%)  1
Lipoma  1  1/4623 (0.02%)  1