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

This study has been completed.
Sponsor:
Collaborators:
Daiichi Sankyo Co., Ltd.
Duke Clinical Research Institute
Information provided by (Responsible Party):
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT00699998
First received: June 16, 2008
Last updated: March 21, 2013
Last verified: March 2013
Results First Received: March 21, 2013  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Acute Coronary Syndrome
Interventions: Drug: Clopidogrel
Drug: Prasugrel
Drug: Commercially-available Aspirin

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Prasugrel: <75 Years of Age

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: 75 Years of Age or Older

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: <75 Years of Age

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: 75 Years of Age or Older

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.


Participant Flow:   Overall Study
    Prasugrel: <75 Years of Age     Prasugrel: 75 Years of Age or Older     Clopidogrel: <75 Years of Age     Clopidogrel: 75 Years of Age or Older  
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  
Withdrawal by Subject                 194                 83                 202                 80  
Physician Decision                 3                 2                 1                 1  
Lost to Follow-up                 2                 1                 3                 1  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Prasugrel: <75 Years of Age 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: 75 Years of Age or Older 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: <75 Years of Age 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: 75 Years of Age or Older 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 Total of all reporting groups

Baseline Measures
    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  
Number of Participants  
[units: participants]
  3620     1043     3623     1040     9326  
Age  
[units: years]
Mean ± Standard Deviation
  61.4  ± 8.55     80.3  ± 4.29     61.5  ± 8.38     80.3  ± 4.39     65.7  ± 11.02  
Gender  
[units: participants]
         
Female     1309     520     1290     531     3650  
Male     2311     523     2333     509     5676  
Race/Ethnicity, Customized  
[units: 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  
[units: 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  
[units: participants]
         
Yes     1393     363     1418     365     3539  
No     2221     678     2193     675     5767  
Unknown     6     2     12     0     20  
History of Myocardial Infarction (MI)  
[units: 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]
[units: participants]
         
Yes     1279     330     1365     299     3273  
No     2332     703     2239     734     6008  
Unknown     9     10     19     7     45  
Clinical Presentation of UA or NSTEMI [2]
[units: 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] History of Coronary Revascularization due to percutaneous coronary intervention (PCI) or coronary artery bypass graft surgery (CABG)
[2] Clinical Presentation of unstable angina (UA) or non-ST-segment elevation myocardial infarction (NSTEMI)



  Outcome Measures
  Hide All Outcome Measures

1.  Primary:   Percentage of Participants With a Composite Endpoint of Cardiovascular (CV) Death, Myocardial Infarction (MI), or Stroke   [ Time Frame: Randomization through end of study (30-month visit) ]

Measure Type Primary
Measure Title Percentage of Participants With a Composite Endpoint of Cardiovascular (CV) Death, Myocardial Infarction (MI), or Stroke
Measure 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)  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All randomized participants

Reporting Groups
  Description
Prasugrel: <75 Years of Age 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: 75 Years of Age or Older 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: <75 Years of Age 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: 75 Years of Age or Older 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.

Measured Values
    Prasugrel: <75 Years of Age     Prasugrel: 75 Years of Age or Older     Clopidogrel: <75 Years of Age     Clopidogrel: 75 Years of Age or Older  
Number of Participants Analyzed  
[units: participants]
  3620     1043     3623     1040  
Percentage of Participants With a Composite Endpoint of Cardiovascular (CV) Death, Myocardial Infarction (MI), or Stroke  
[units: percentage of participants with an event]
  10.06     24.64     10.96     24.13  


Statistical Analysis 1 for Percentage of Participants With a Composite Endpoint of Cardiovascular (CV) Death, Myocardial Infarction (MI), or Stroke
Groups [1] Prasugrel: <75 Years of Age vs. Clopidogrel: <75 Years of Age
Method [2] Log Rank
P Value [3] 0.210
Hazard Ratio (HR) [4] 0.915
95% Confidence Interval ( 0.793 to 1.055 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Two-sided p-value based on a log-rank test stratified by clopidogrel status at randomization.
[4] Other relevant estimation information:
  HR and two-sided 95% CI derived using Cox proportional hazards model with treatment and clopidogrel status at randomization as fixed effects.

Statistical Analysis 2 for Percentage of Participants With a Composite Endpoint of Cardiovascular (CV) Death, Myocardial Infarction (MI), or Stroke
Groups [1] Prasugrel: 75 Years of Age or Older vs. Clopidogrel: 75 Years of Age or Older
Method [2] Log Rank
P Value [3] 0.731
Hazard Ratio (HR) [4] 1.029
95% Confidence Interval ( 0.865 to 1.225 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Two-sided p-value based on a log-rank test stratified by clopidogrel status at randomization.
[4] Other relevant estimation information:
  HR and two-sided 95% CI derived using Cox proportional hazards model with treatment and clopidogrel status at randomization as fixed effects.



2.  Secondary:   Percentage of Participants With a Composite Endpoint of CV Death and MI   [ Time Frame: Randomization through end of study (30-month visit) ]

Measure Type Secondary
Measure Title Percentage of Participants With a Composite Endpoint of CV Death and MI
Measure 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)  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All randomized participants

Reporting Groups
  Description
Prasugrel: <75 Years of Age 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: 75 Years of Age or Older 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: <75 Years of Age 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: 75 Years of Age or Older 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.

Measured Values
    Prasugrel: <75 Years of Age     Prasugrel: 75 Years of Age or Older     Clopidogrel: <75 Years of Age     Clopidogrel: 75 Years of Age or Older  
Number of Participants Analyzed  
[units: participants]
  3620     1043     3623     1040  
Percentage of Participants With a Composite Endpoint of CV Death and MI  
[units: percentage of participants with an event]
  9.61     22.53     10.21     22.69  


Statistical Analysis 1 for Percentage of Participants With a Composite Endpoint of CV Death and MI
Groups [1] Prasugrel: <75 Years of Age vs. Clopidogrel: <75 Years of Age
Method [2] Log Rank
P Value [3] 0.388
Hazard Ratio (HR) [4] 0.940
95% Confidence Interval ( 0.812 to 1.088 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  Two-sided p-value based on a log-rank test stratified by clopidogrel status at randomization.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  HR and two-sided 95% CI derived using Cox proportional hazards model with treatment and clopidogrel status at randomization as fixed effects.

Statistical Analysis 2 for Percentage of Participants With a Composite Endpoint of CV Death and MI
Groups [1] Prasugrel: 75 Years of Age or Older vs. Clopidogrel: 75 Years of Age or Older
Method [2] Log Rank
P Value [3] 0.990
Hazard Ratio (HR) [4] 0.998
95% Confidence Interval ( 0.833 to 1.195 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Two-sided p-value based on a log-rank test stratified by clopidogrel status at randomization.
[4] Other relevant estimation information:
  HR and two-sided 95% CI derived using Cox proportional hazards model with treatment and clopidogrel status at randomization as fixed effects.



3.  Secondary:   Percentage of Participants With a Composite Endpoint of CV Death, MI, Stroke, or Re-hospitalization for Recurrent Unstable Angina (UA)   [ Time Frame: Randomization through end of study (30-month visit) ]

Measure Type Secondary
Measure Title Percentage of Participants With a Composite Endpoint of CV Death, MI, Stroke, or Re-hospitalization for Recurrent Unstable Angina (UA)
Measure 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)  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All randomized participants

Reporting Groups
  Description
Prasugrel: <75 Years of Age 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: 75 Years of Age or Older 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: <75 Years of Age 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: 75 Years of Age or Older 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.

Measured Values
    Prasugrel: <75 Years of Age     Prasugrel: 75 Years of Age or Older     Clopidogrel: <75 Years of Age     Clopidogrel: 75 Years of Age or Older  
Number of Participants Analyzed  
[units: participants]
  3620     1043     3623     1040  
Percentage of Participants With a Composite Endpoint of CV Death, MI, Stroke, or Re-hospitalization for Recurrent Unstable Angina (UA)  
[units: percentage of participants with an event]
  12.13     26.27     12.83     25.67  


Statistical Analysis 1 for Percentage of Participants With a Composite Endpoint of CV Death, MI, Stroke, or Re-hospitalization for Recurrent Unstable Angina (UA)
Groups [1] Prasugrel: <75 Years of Age vs. Clopidogrel: <75 Years of Age
Method [2] Log Rank
P Value [3] 0.353
Hazard Ratio (HR) [4] 0.941
95% Confidence Interval ( 0.826 to 1.073 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Two-sided p-value based on a log-rank test stratified by clopidogrel status at randomization.
[4] Other relevant estimation information:
  HR and two-sided 95% CI derived using Cox proportional hazards model with treatment and clopidogrel status at randomization as fixed effects.

Statistical Analysis 2 for Percentage of Participants With a Composite Endpoint of CV Death, MI, Stroke, or Re-hospitalization for Recurrent Unstable Angina (UA)
Groups [1] Prasugrel: 75 Years of Age or Older vs. Clopidogrel: 75 Years of Age or Older
Method [2] Log Rank
P Value [3] 0.719
Hazard Ratio (HR) [4] 1.029
95% Confidence Interval ( 0.869 to 1.218 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Two-sided p-value based on a log-rank test stratified by clopidogrel status at randomization.
[4] Other relevant estimation information:
  HR and two-sided 95% CI derived using Cox proportional hazards model with treatment and clopidogrel status at randomization as fixed effects.



4.  Secondary:   Percentage of Participants With a Composite Endpoint of All-cause Death, MI, or Stroke   [ Time Frame: Randomization through end of study (30-month visit) ]

Measure Type Secondary
Measure Title Percentage of Participants With a Composite Endpoint of All-cause Death, MI, or Stroke
Measure 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)  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All randomized participants

Reporting Groups
  Description
Prasugrel: <75 Years of Age 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: 75 Years of Age or Older 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: <75 Years of Age 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: 75 Years of Age or Older 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.

Measured Values
    Prasugrel: <75 Years of Age     Prasugrel: 75 Years of Age or Older     Clopidogrel: <75 Years of Age     Clopidogrel: 75 Years of Age or Older  
Number of Participants Analyzed  
[units: participants]
  3620     1043     3623     1040  
Percentage of Participants With a Composite Endpoint of All-cause Death, MI, or Stroke  
[units: percentage of participants with an event]
  10.61     27.04     11.12     26.83  


Statistical Analysis 1 for Percentage of Participants With a Composite Endpoint of All-cause Death, MI, or Stroke
Groups [1] Prasugrel: <75 Years of Age vs. Clopidogrel: <75 Years of Age
Method [2] Log Rank
P Value [3] 0.270
Hazard Ratio (HR) [4] 0.928
95% Confidence Interval ( 0.810 to 1.063 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Two-sided p-value based on a log-rank test stratified by clopidogrel status at randomization.
[4] Other relevant estimation information:
  HR and two-sided 95% CI derived using Cox proportional hazards model with treatment and clopidogrel status at randomization as fixed effects.

Statistical Analysis 2 for Percentage of Participants With a Composite Endpoint of All-cause Death, MI, or Stroke
Groups [1] Prasugrel: 75 Years of Age or Older vs. Clopidogrel: 75 Years of Age or Older
Method [2] Log Rank
P Value [3] 0.831
Hazard Ratio (HR) [4] 1.017
95% Confidence Interval ( 0.862 to 1.200 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Two-sided p-value based on a log-rank test stratified by clopidogrel status at randomization.
[4] Other relevant estimation information:
  HR and two-sided 95% CI derived using Cox proportional hazards model with treatment and clopidogrel status at randomization as fixed effects.



5.  Secondary:   Platelet Aggregation Measures   [ Time Frame: Day 30 and 12 Months ]

Measure Type Secondary
Measure Title Platelet Aggregation Measures
Measure 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups
  Description
Prasugrel: <75 Years of Age 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: 75 Years of Age or Older 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: <75 Years of Age 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: 75 Years of Age or Older 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.

Measured Values
    Prasugrel: <75 Years of Age     Prasugrel: 75 Years of Age or Older     Clopidogrel: <75 Years of Age     Clopidogrel: 75 Years of Age or Older  
Number of Participants Analyzed  
[units: participants]
  720     158     683     179  
Platelet Aggregation Measures  
[units: P2Y12 Reaction Units (PRU)]
Least Squares Mean ± Standard Error
       
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  


Statistical Analysis 1 for Platelet Aggregation Measures
Groups [1] Prasugrel: <75 Years of Age vs. Clopidogrel: <75 Years of Age
Method [2] ANCOVA
P Value [3] <0.001
Mean Difference (Final Values) [4] -100.208
95% Confidence Interval ( -107.872 to -92.545 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  p-value is for Day 30 comparison. ANCOVA Model: Measurement = treatment + baseline value + clopidogrel status at randomization.
[4] Other relevant estimation information:
  Estimated Mean Difference (Final Values) for Day 30 comparison

Statistical Analysis 2 for Platelet Aggregation Measures
Groups [1] Prasugrel: <75 Years of Age vs. Clopidogrel: <75 Years of Age
Method [2] ANCOVA
P Value [3] <0.001
Mean Difference (Final Values) [4] -104.475
95% Confidence Interval ( -115.383 to -93.566 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  p-value is for 12 month comparison. ANCOVA Model: Measurement = treatment + baseline value + clopidogrel status at randomization.
[4] Other relevant estimation information:
  Estimated Mean Difference (Final Values) for 12 month comparison.

Statistical Analysis 3 for Platelet Aggregation Measures
Groups [1] Prasugrel: 75 Years of Age or Older vs. Clopidogrel: 75 Years of Age or Older
Method [2] ANCOVA
P Value [3] <0.001
Mean Difference (Final Values) [4] -48.413
95% Confidence Interval ( -63.718 to -33.108 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  p-value is for 30 day comparison. ANCOVA Model: Measurement = treatment + baseline value + clopidogrel status at randomization.
[4] Other relevant estimation information:
  Estimated Mean Difference (Final Values) is for the 30 day comparison.

Statistical Analysis 4 for Platelet Aggregation Measures
Groups [1] Prasugrel: 75 Years of Age or Older vs. Clopidogrel: 75 Years of Age or Older
Method [2] ANCOVA
P Value [3] <0.001
Mean Difference (Final Values) [4] -46.264
95% Confidence Interval ( -69.061 to -23.468 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  p-value is for the 12 month comparison. ANCOVA Model: Measurement = treatment + baseline value + clopidogrel status at randomization.
[4] Other relevant estimation information:
  Estimated Mean Difference (Final Values) is for the 12 month comparison.



6.  Secondary:   Biomarker Measurements of Inflammation/Hemodynamic Stress: Brain Natriuretic Peptide (BNP)   [ Time Frame: Day 30 and 6 Months ]

Measure Type Secondary
Measure Title Biomarker Measurements of Inflammation/Hemodynamic Stress: Brain Natriuretic Peptide (BNP)
Measure 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups
  Description
Prasugrel: <75 Years of Age 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: 75 Years of Age or Older 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: <75 Years of Age 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: 75 Years of Age or Older 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.

Measured Values
    Prasugrel: <75 Years of Age     Prasugrel: 75 Years of Age or Older     Clopidogrel: <75 Years of Age     Clopidogrel: 75 Years of Age or Older  
Number of Participants Analyzed  
[units: participants]
  859     196     840     224  
Biomarker Measurements of Inflammation/Hemodynamic Stress: Brain Natriuretic Peptide (BNP)  
[units: picograms per milliliter (pg/mL)]
Geometric Mean ± Standard Error
       
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  


Statistical Analysis 1 for Biomarker Measurements of Inflammation/Hemodynamic Stress: Brain Natriuretic Peptide (BNP)
Groups [1] Prasugrel: <75 Years of Age vs. Clopidogrel: <75 Years of Age
Method [2] ANCOVA
P Value [3] 0.631
Geometric Ratio Estimate [4] 0.982
95% Confidence Interval ( 0.910 to 1.059 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  p-value is for the 30 day comparison. ANCOVA Model: Measurement = treatment + baseline value + clopidogrel status at randomization.
[4] Other relevant estimation information:
  Geometric Ratio Estimate is for the 30 day comparison.

Statistical Analysis 2 for Biomarker Measurements of Inflammation/Hemodynamic Stress: Brain Natriuretic Peptide (BNP)
Groups [1] Prasugrel: <75 Years of Age vs. Clopidogrel: <75 Years of Age
Method [2] ANCOVA
P Value [3] 0.844
Geometric Ratio Estimate [4] 1.010
95% Confidence Interval ( 0.916 to 1.113 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  p-value is for the 6 month comparison. ANCOVA Model: Measurement = treatment + baseline value + clopidogrel status at randomization.
[4] Other relevant estimation information:
  Geometric Ratio Estimate is for the 6 month comparison.

Statistical Analysis 3 for Biomarker Measurements of Inflammation/Hemodynamic Stress: Brain Natriuretic Peptide (BNP)
Groups [1] Prasugrel: 75 Years of Age or Older vs. Clopidogrel: 75 Years of Age or Older
Method [2] ANCOVA
P Value [3] 0.098
Geometric Ratio Estimate [4] 1.138
95% Confidence Interval ( 0.977 to 1.325 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  p-value is for the 30 day comparison. ANCOVA Model: Measurement = treatment + baseline value + clopidogrel status at randomization.
[4] Other relevant estimation information:
  Geometric Ratio Estimate is for the 30 day comparison.

Statistical Analysis 4 for Biomarker Measurements of Inflammation/Hemodynamic Stress: Brain Natriuretic Peptide (BNP)
Groups [1] Prasugrel: 75 Years of Age or Older vs. Clopidogrel: 75 Years of Age or Older
Method [2] ANCOVA
P Value [3] 0.545
Geometric Ratio Estimate [4] 1.066
95% Confidence Interval ( 0.867 to 1.310 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  p-value is for the 6 month comparison. ANCOVA Model: Measurement = treatment + baseline value + clopidogrel status at randomization.
[4] Other relevant estimation information:
  Geometric Ratio Estimate is for the 6 month comparison.



7.  Secondary:   Biomarker Measurements of Inflammation/Hemodynamic Stress: C-Reactive Protein (CRP)   [ Time Frame: Day 30 and Month 6 ]

Measure Type Secondary
Measure Title Biomarker Measurements of Inflammation/Hemodynamic Stress: C-Reactive Protein (CRP)
Measure 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups
  Description
Prasugrel: <75 Years of Age 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: 75 Years of Age or Older 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: <75 Years of Age 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: 75 Years of Age or Older 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.

Measured Values
    Prasugrel: <75 Years of Age     Prasugrel: 75 Years of Age or Older     Clopidogrel: <75 Years of Age     Clopidogrel: 75 Years of Age or Older  
Number of Participants Analyzed  
[units: participants]
  888     209     863     226  
Biomarker Measurements of Inflammation/Hemodynamic Stress: C-Reactive Protein (CRP)  
[units: milligrams per liter (mg/L)]
Geometric Mean ± Standard Error
       
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  


Statistical Analysis 1 for Biomarker Measurements of Inflammation/Hemodynamic Stress: C-Reactive Protein (CRP)
Groups [1] Prasugrel: <75 Years of Age vs. Clopidogrel: <75 Years of Age
Method [2] ANCOVA
P Value [3] 0.727
Geometric Ratio Estimate [4] 1.018
95% Confidence Interval ( 0.919 to 1.129 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  p-value is for the 30 day comparison. ANCOVA Model: Measurement = treatment + baseline value + clopidogrel status at randomization.
[4] Other relevant estimation information:
  Geometric Ratio Estimate is for the 30 day comparison.

Statistical Analysis 2 for Biomarker Measurements of Inflammation/Hemodynamic Stress: C-Reactive Protein (CRP)
Groups [1] Prasugrel: <75 Years of Age vs. Clopidogrel: <75 Years of Age
Method [2] ANCOVA
P Value [3] 0.346
Geometric Ratio Estimate [4] 1.057
95% Confidence Interval ( 0.942 to 1.187 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  p-value is for the 6 month comparison. ANCOVA Model: Measurement = treatment + baseline value + clopidogrel status at randomization.
[4] Other relevant estimation information:
  Geometric Ratio Estimate is for the 6 month comparison.

Statistical Analysis 3 for Biomarker Measurements of Inflammation/Hemodynamic Stress: C-Reactive Protein (CRP)
Groups [1] Prasugrel: 75 Years of Age or Older vs. Clopidogrel: 75 Years of Age or Older
Method [2] ANCOVA
P Value [3] 0.458
Geometric Ratio Estimate [4] 1.096
95% Confidence Interval ( 0.859 to 1.399 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  p-value is for the 30 day comparison. ANCOVA Model: Measurement = treatment + baseline value + clopidogrel status at randomization.
[4] Other relevant estimation information:
  Geometric Ratio Estimate is for the 30 day comparison.

Statistical Analysis 4 for Biomarker Measurements of Inflammation/Hemodynamic Stress: C-Reactive Protein (CRP)
Groups [1] Prasugrel: 75 Years of Age or Older vs. Clopidogrel: 75 Years of Age or Older
Method [2] ANCOVA
P Value [3] 0.802
Geometric Ratio Estimate [4] 1.033
95% Confidence Interval ( 0.803 to 1.329 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  p-value is for the 6 month comparison. ANCOVA Model: Measurement = treatment + baseline value + clopidogrel status at randomization.
[4] Other relevant estimation information:
  Geometric Ratio Estimate is for the 6 month comparison.



8.  Secondary:   Genotyping Related to Drug Metabolism   [ Time Frame: Baseline ]

Measure Type Secondary
Measure Title Genotyping Related to Drug Metabolism
Measure 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All randomized participants who provided a DNA sample.

Reporting Groups
  Description
Prasugrel: <75 Years of Age 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: 75 Years of Age or Older 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: <75 Years of Age 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: 75 Years of Age or Older 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.

Measured Values
    Prasugrel: <75 Years of Age     Prasugrel: 75 Years of Age or Older     Clopidogrel: <75 Years of Age     Clopidogrel: 75 Years of Age or Older  
Number of Participants Analyzed  
[units: participants]
  2210     639     2237     650  
Genotyping Related to Drug Metabolism  
[units: 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  

No statistical analysis provided for Genotyping Related to Drug Metabolism



9.  Secondary:   Economic and Quality of Life Outcomes   [ Time Frame: Baseline and follow-up (24 months) ]

Measure Type Secondary
Measure Title Economic and Quality of Life Outcomes
Measure 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)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All randomized participants (combined <75 years and 75 years and older) with SAQ data.

Reporting Groups
  Description
Prasugrel 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 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.

Measured Values
    Prasugrel     Clopidogrel  
Number of Participants Analyzed  
[units: participants]
  1506     1506  
Economic and Quality of Life Outcomes  
[units: units on a scale]
Mean ± Standard Deviation
   
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  


Statistical Analysis 1 for Economic and Quality of Life Outcomes
Groups [1] All groups
Method [2] ANCOVA
P Value [3] 0.5
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  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.

Statistical Analysis 2 for Economic and Quality of Life Outcomes
Groups [1] All groups
Method [2] ANCOVA
P Value [3] 0.72
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  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.

Statistical Analysis 3 for Economic and Quality of Life Outcomes
Groups [1] All groups
Method [2] ANCOVA
P Value [3] 0.63
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  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.

Statistical Analysis 4 for Economic and Quality of Life Outcomes
Groups [1] All groups
Method [2] ANCOVA
P Value [3] 0.53
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  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.



10.  Secondary:   Summary of All Deaths   [ Time Frame: Randomization through end of study (30-month visit) ]

Measure Type Secondary
Measure Title Summary of All Deaths
Measure 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)  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All randomized participants

Reporting Groups
  Description
Prasugrel: <75 Years of Age

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: 75 Years of Age or Older

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: <75 Years of Age

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: 75 Years of Age or Older

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.


Measured Values
    Prasugrel: <75 Years of Age     Prasugrel: 75 Years of Age or Older     Clopidogrel: <75 Years of Age     Clopidogrel: 75 Years of Age or Older  
Number of Participants Analyzed  
[units: participants]
  3620     1043     3623     1040  
Summary of All Deaths  
[units: 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  

No statistical analysis provided for Summary of All Deaths




  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.


  More Information