Acute Coronary Syndrome
Conditions
Keywords
ACS
Brief summary
This study will evaluate the relative efficacy and safety of prasugrel and clopidogrel in a medically managed Unstable Angina/Non-ST-Elevation Myocardial Infarction (UA/NSTEMI) acute coronary syndrome (ACS) population (that is, patients who are not managed with acute coronary revascularization).
Detailed description
Based upon the significant number of subjects with UA/NSTEMI ACS who are managed medically and their high risk for future cardiovascular events, further exploration of novel treatment strategies for this population, who are under-represented in large clinical trials, is warranted. Potential subjects will be those with a recent UA/NSTEMI event who are to be medically managed. Eligibility for this study will be determined by both the timing of the medical management decision and by prior commercial clopidogrel treatment at the time of randomization. The TaRgeted platelet Inhibition to cLarify the Optimal strateGy to medicallY manage Acute Coronary Syndromes (TRILOGY ACS) Study will assess the efficacy and safety of prasugrel and aspirin compared to the current standard of care, clopidogrel and aspirin, for long-term treatment of medically managed UA/NSTEMI ACS subjects.
Interventions
DRUGClopidogrel
300 milligrams (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
DRUGPrasugrel
30 milligrams (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
DRUGCommercially-available Aspirin
Low-dose aspirin, oral, as prescribed by physician through end of study
Sponsors
Daiichi Sankyo Co., Ltd.
Duke Clinical Research Institute
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Have had a Unstable Angina/Non-ST-Elevation Myocardial Infarction (UA/NSTEMI) index event within 10 days prior to randomization * Had a medical management strategy decision made with reasonable certainty that neither percutaneous coronary intervention (PCI) nor coronary artery bypass graft (CABG) is planned for treatment of the index event * Had at least 1 of 4 specified high-risk features at the time of the UA/NSTEMI event Key
Exclusion criteria
* Decision for medical management greater than 72 hours after onset of index event without commercial clopidogrel treatment within 72 hours following onset of the index event. * Insignificant coronary artery disease (CAD) on coronary angiography if performed for Index Event (absence of greater than or equal to 30% stenosis in at least one native vessel) * Previous or planned PCI or CABG as treatment for the index event * PCI/CABG within previous 30 days * ST-segment elevation myocardial infarction (STEMI) as the index event * Cardiogenic shock, Refractory ventricular arrhythmias, New York Heart Association (NYHA) Class IV congestive heart failure (CHF) within the previous 24 hours * History of ischemic or hemorrhagic stroke, transient ischemic attack (TIA), Intracranial neoplasm, arteriovenous malformation, or aneurysm * History of spontaneous gastrointestinal (GI) or non-GI bleeding requiring hospitalization for treatment, unless definitive treatment has occurred and there is low likelihood of recurrence * Hemodialysis or peritoneal dialysis
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With a Composite Endpoint of Cardiovascular (CV) Death, Myocardial Infarction (MI), or Stroke | Randomization through end of study (30-month visit) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With a Composite Endpoint of CV Death, MI, Stroke, or Re-hospitalization for Recurrent Unstable Angina (UA) | Randomization through end of study (30-month visit) | 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. |
| Percentage of Participants With a Composite Endpoint of All-cause Death, MI, or Stroke | Randomization through end of study (30-month visit) | 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. |
| Platelet Aggregation Measures | Day 30 and 12 Months | 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. |
| Biomarker Measurements of Inflammation/Hemodynamic Stress: Brain Natriuretic Peptide (BNP) | Day 30 and 6 Months | 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. |
| Percentage of Participants With a Composite Endpoint of CV Death and MI | Randomization through end of study (30-month visit) | 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. |
| Genotyping Related to Drug Metabolism | Baseline | 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. |
| Economic and Quality of Life Outcomes | Baseline and follow-up (24 months) | 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. |
| Summary of All Deaths | Randomization through end of study (30-month visit) | 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. |
| Biomarker Measurements of Inflammation/Hemodynamic Stress: C-Reactive Protein (CRP) | Day 30 and Month 6 | 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. |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Canada, Chile, China, Colombia, Costa Rica, Croatia, Czechia, Denmark, Egypt, Finland, France, Germany, Greece, Hungary, India, Ireland, Israel, Italy, Lithuania, Malaysia, Malta, Mexico, Netherlands, New Zealand, Panama, Peru, Philippines, Poland, Portugal, Puerto Rico, Romania, Russia, Serbia, Singapore, Slovakia, South Africa, South Korea, Spain, Sweden, Switzerland, Taiwan, Thailand, Tunisia, Turkey (Türkiye), Ukraine, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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. | 3,620 |
| 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. | 1,043 |
| 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. | 3,623 |
| 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. | 1,040 |
| Total | 9,326 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 2 | 1 | 3 | 1 |
| Overall Study | Physician Decision | 3 | 2 | 1 | 1 |
| Overall Study | Withdrawal by Subject | 194 | 83 | 202 | 80 |
Baseline characteristics
| Characteristic | Prasugrel: 75 Years of Age or Older | Total | Clopidogrel: 75 Years of Age or Older | Prasugrel: <75 Years of Age | Clopidogrel: <75 Years of Age |
|---|---|---|---|---|---|
| Age Continuous | 80.3 years STANDARD_DEVIATION 4.29 | 65.7 years STANDARD_DEVIATION 11.02 | 80.3 years STANDARD_DEVIATION 4.39 | 61.4 years STANDARD_DEVIATION 8.55 | 61.5 years STANDARD_DEVIATION 8.38 |
| Clinical Presentation of UA or NSTEMI Non-ST-segment Elevation Myocardial Infarction | 829 participants | 6520 participants | 804 participants | 2453 participants | 2434 participants |
| Clinical Presentation of UA or NSTEMI Unknown/Did not meet criteria | 48 participants | 504 participants | 44 participants | 204 participants | 208 participants |
| Clinical Presentation of UA or NSTEMI Unstable Angina | 166 participants | 2302 participants | 192 participants | 963 participants | 981 participants |
| History of Coronary Revascularization (PCI or CABG) No | 703 participants | 6008 participants | 734 participants | 2332 participants | 2239 participants |
| History of Coronary Revascularization (PCI or CABG) Unknown | 10 participants | 45 participants | 7 participants | 9 participants | 19 participants |
| History of Coronary Revascularization (PCI or CABG) Yes | 330 participants | 3273 participants | 299 participants | 1279 participants | 1365 participants |
| History of Diabetes No | 678 participants | 5767 participants | 675 participants | 2221 participants | 2193 participants |
| History of Diabetes Unknown | 2 participants | 20 participants | 0 participants | 6 participants | 12 participants |
| History of Diabetes Yes | 363 participants | 3539 participants | 365 participants | 1393 participants | 1418 participants |
| History of Myocardial Infarction (MI) No | 603 participants | 5259 participants | 633 participants | 2035 participants | 1988 participants |
| History of Myocardial Infarction (MI) Unknown | 14 participants | 80 participants | 14 participants | 29 participants | 23 participants |
| History of Myocardial Infarction (MI) Yes | 426 participants | 3987 participants | 393 participants | 1556 participants | 1612 participants |
| Race/Ethnicity, Customized African | 14 participants | 185 participants | 12 participants | 87 participants | 72 participants |
| Race/Ethnicity, Customized Asian | 147 participants | 1932 participants | 164 participants | 821 participants | 800 participants |
| Race/Ethnicity, Customized Caucasian | 767 participants | 6276 participants | 773 participants | 2362 participants | 2374 participants |
| Race/Ethnicity, Customized Hispanic | 109 participants | 862 participants | 86 participants | 321 participants | 346 participants |
| Race/Ethnicity, Customized Other | 6 participants | 70 participants | 5 participants | 29 participants | 30 participants |
| Race/Ethnicity, Customized Unknown | 0 participants | 1 participants | 0 participants | 0 participants | 1 participants |
| Region of Enrollment Argentina | 58 participants | 357 participants | 41 participants | 120 participants | 138 participants |
| Region of Enrollment Australia | 6 participants | 41 participants | 7 participants | 13 participants | 15 participants |
| Region of Enrollment Austria | 6 participants | 23 participants | 5 participants | 6 participants | 6 participants |
| Region of Enrollment Belgium | 7 participants | 29 participants | 8 participants | 7 participants | 7 participants |
| Region of Enrollment Brazil | 27 participants | 362 participants | 34 participants | 154 participants | 147 participants |
| Region of Enrollment Bulgaria | 48 participants | 528 participants | 55 participants | 216 participants | 209 participants |
| Region of Enrollment Canada | 14 participants | 146 participants | 13 participants | 58 participants | 61 participants |
| Region of Enrollment Chile | 15 participants | 89 participants | 13 participants | 28 participants | 33 participants |
| Region of Enrollment China | 38 participants | 328 participants | 44 participants | 126 participants | 120 participants |
| Region of Enrollment Colombia | 21 participants | 123 participants | 17 participants | 40 participants | 45 participants |
| Region of Enrollment Costa Rica | 1 participants | 10 participants | 2 participants | 5 participants | 2 participants |
| Region of Enrollment Croatia | 28 participants | 182 participants | 31 participants | 63 participants | 60 participants |
| Region of Enrollment Czech Republic | 31 participants | 138 participants | 38 participants | 37 participants | 32 participants |
| Region of Enrollment Denmark | 7 participants | 55 participants | 10 participants | 21 participants | 17 participants |
| Region of Enrollment Egypt | 1 participants | 132 participants | 4 participants | 65 participants | 62 participants |
| Region of Enrollment Finland | 3 participants | 13 participants | 2 participants | 3 participants | 5 participants |
| Region of Enrollment France | 22 participants | 99 participants | 19 participants | 29 participants | 29 participants |
| Region of Enrollment Germany | 20 participants | 133 participants | 21 participants | 46 participants | 46 participants |
| Region of Enrollment Greece | 8 participants | 43 participants | 11 participants | 14 participants | 10 participants |
| Region of Enrollment Hungary | 43 participants | 260 participants | 44 participants | 86 participants | 87 participants |
| Region of Enrollment India | 56 participants | 1141 participants | 64 participants | 513 participants | 508 participants |
| Region of Enrollment Ireland | 4 participants | 18 participants | 3 participants | 5 participants | 6 participants |
| Region of Enrollment Israel | 33 participants | 214 participants | 21 participants | 75 participants | 85 participants |
| Region of Enrollment Italy | 44 participants | 232 participants | 47 participants | 71 participants | 70 participants |
| Region of Enrollment Korea, Republic of | 7 participants | 82 participants | 7 participants | 35 participants | 33 participants |
| Region of Enrollment Lithuania | 8 participants | 73 participants | 4 participants | 29 participants | 32 participants |
| Region of Enrollment Malaysia | 7 participants | 84 participants | 9 participants | 35 participants | 33 participants |
| Region of Enrollment Malta | 1 participants | 22 participants | 2 participants | 9 participants | 10 participants |
| Region of Enrollment Mexico | 15 participants | 109 participants | 16 participants | 38 participants | 40 participants |
| Region of Enrollment Netherlands | 23 participants | 155 participants | 24 participants | 55 participants | 53 participants |
| Region of Enrollment New Zealand | 3 participants | 26 participants | 3 participants | 10 participants | 10 participants |
| Region of Enrollment Panama | 7 participants | 70 participants | 10 participants | 29 participants | 24 participants |
| Region of Enrollment Peru | 19 participants | 156 participants | 12 participants | 58 participants | 67 participants |
| Region of Enrollment Philippines | 7 participants | 127 participants | 14 participants | 58 participants | 48 participants |
| Region of Enrollment Poland | 59 participants | 393 participants | 68 participants | 137 participants | 129 participants |
| Region of Enrollment Portugal | 11 participants | 54 participants | 11 participants | 18 participants | 14 participants |
| Region of Enrollment Romania | 26 participants | 257 participants | 23 participants | 103 participants | 105 participants |
| Region of Enrollment Russian Federation | 22 participants | 299 participants | 14 participants | 128 participants | 135 participants |
| Region of Enrollment Serbia | 4 participants | 91 participants | 5 participants | 42 participants | 40 participants |
| Region of Enrollment Singapore | 5 participants | 13 participants | 1 participants | 2 participants | 5 participants |
| Region of Enrollment Slovakia | 20 participants | 162 participants | 20 participants | 62 participants | 60 participants |
| Region of Enrollment South Africa | 11 participants | 77 participants | 12 participants | 27 participants | 27 participants |
| Region of Enrollment Spain | 8 participants | 43 participants | 12 participants | 13 participants | 10 participants |
| Region of Enrollment Sweden | 3 participants | 14 participants | 1 participants | 4 participants | 6 participants |
| Region of Enrollment Switzerland | 4 participants | 20 participants | 6 participants | 6 participants | 4 participants |
| Region of Enrollment Taiwan | 6 participants | 25 participants | 9 participants | 6 participants | 4 participants |
| Region of Enrollment Thailand | 17 participants | 93 participants | 10 participants | 30 participants | 36 participants |
| Region of Enrollment Tunisia | 3 participants | 47 participants | 4 participants | 20 participants | 20 participants |
| Region of Enrollment Turkey | 24 participants | 200 participants | 19 participants | 76 participants | 81 participants |
| Region of Enrollment Ukraine | 28 participants | 707 participants | 42 participants | 326 participants | 311 participants |
| Region of Enrollment United Kingdom | 21 participants | 106 participants | 12 participants | 33 participants | 40 participants |
| Region of Enrollment United States | 133 participants | 1125 participants | 116 participants | 430 participants | 446 participants |
| Sex: Female, Male Female | 520 Participants | 3650 Participants | 531 Participants | 1309 Participants | 1290 Participants |
| Sex: Female, Male Male | 523 Participants | 5676 Participants | 509 Participants | 2311 Participants | 2333 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 2,581 / 4,623 | 2,494 / 4,617 |
| serious Total, serious adverse events | 1,573 / 4,623 | 1,594 / 4,617 |
Outcome results
Primary
Percentage of Participants With a Composite Endpoint of Cardiovascular (CV) Death, Myocardial Infarction (MI), or Stroke
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)
Population: All randomized participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Prasugrel: <75 Years of Age | Percentage of Participants With a Composite Endpoint of Cardiovascular (CV) Death, Myocardial Infarction (MI), or Stroke | 10.06 percentage of participants with an event |
| Prasugrel: 75 Years of Age or Older | Percentage of Participants With a Composite Endpoint of Cardiovascular (CV) Death, Myocardial Infarction (MI), or Stroke | 24.64 percentage of participants with an event |
| Clopidogrel: <75 Years of Age | Percentage of Participants With a Composite Endpoint of Cardiovascular (CV) Death, Myocardial Infarction (MI), or Stroke | 10.96 percentage of participants with an event |
| Clopidogrel: 75 Years of Age or Older | Percentage of Participants With a Composite Endpoint of Cardiovascular (CV) Death, Myocardial Infarction (MI), or Stroke | 24.13 percentage of participants with an event |
p-value: 0.2195% CI: [0.793, 1.055]Log Rank
p-value: 0.73195% CI: [0.865, 1.225]Log Rank
Secondary
Biomarker Measurements of Inflammation/Hemodynamic Stress: Brain Natriuretic Peptide (BNP)
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
Population: 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 | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Prasugrel: <75 Years of Age | Biomarker Measurements of Inflammation/Hemodynamic Stress: Brain Natriuretic Peptide (BNP) | Day 30 | 313.494 picograms per milliliter (pg/mL) | Standard Error 1.039 |
| Prasugrel: <75 Years of Age | Biomarker Measurements of Inflammation/Hemodynamic Stress: Brain Natriuretic Peptide (BNP) | 6 Months (n=725, 125, 701, 174) | 253.434 picograms per milliliter (pg/mL) | Standard Error 1.049 |
| Prasugrel: 75 Years of Age or Older | Biomarker Measurements of Inflammation/Hemodynamic Stress: Brain Natriuretic Peptide (BNP) | 6 Months (n=725, 125, 701, 174) | 770.132 picograms per milliliter (pg/mL) | Standard Error 1.135 |
| Prasugrel: 75 Years of Age or Older | Biomarker Measurements of Inflammation/Hemodynamic Stress: Brain Natriuretic Peptide (BNP) | Day 30 | 1082.396 picograms per milliliter (pg/mL) | Standard Error 1.093 |
| Clopidogrel: <75 Years of Age | Biomarker Measurements of Inflammation/Hemodynamic Stress: Brain Natriuretic Peptide (BNP) | Day 30 | 319.345 picograms per milliliter (pg/mL) | Standard Error 1.039 |
| Clopidogrel: <75 Years of Age | Biomarker Measurements of Inflammation/Hemodynamic Stress: Brain Natriuretic Peptide (BNP) | 6 Months (n=725, 125, 701, 174) | 250.982 picograms per milliliter (pg/mL) | Standard Error 1.049 |
| Clopidogrel: 75 Years of Age or Older | Biomarker Measurements of Inflammation/Hemodynamic Stress: Brain Natriuretic Peptide (BNP) | Day 30 | 951.359 picograms per milliliter (pg/mL) | Standard Error 1.092 |
| Clopidogrel: 75 Years of Age or Older | Biomarker Measurements of Inflammation/Hemodynamic Stress: Brain Natriuretic Peptide (BNP) | 6 Months (n=725, 125, 701, 174) | 722.750 picograms per milliliter (pg/mL) | Standard Error 1.13 |
p-value: 0.63195% CI: [0.91, 1.059]ANCOVA
p-value: 0.84495% CI: [0.916, 1.113]ANCOVA
p-value: 0.09895% CI: [0.977, 1.325]ANCOVA
p-value: 0.54595% CI: [0.867, 1.31]ANCOVA
Secondary
Biomarker Measurements of Inflammation/Hemodynamic Stress: C-Reactive Protein (CRP)
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
Population: 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 | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Prasugrel: <75 Years of Age | Biomarker Measurements of Inflammation/Hemodynamic Stress: C-Reactive Protein (CRP) | 6 Months (n=755, 143, 745, 178) | 2.272 milligrams per liter (mg/L) | Standard Error 1.06 |
| Prasugrel: <75 Years of Age | Biomarker Measurements of Inflammation/Hemodynamic Stress: C-Reactive Protein (CRP) | Day 30 | 2.330 milligrams per liter (mg/L) | Standard Error 1.053 |
| Prasugrel: 75 Years of Age or Older | Biomarker Measurements of Inflammation/Hemodynamic Stress: C-Reactive Protein (CRP) | Day 30 | 2.441 milligrams per liter (mg/L) | Standard Error 1.15 |
| Prasugrel: 75 Years of Age or Older | Biomarker Measurements of Inflammation/Hemodynamic Stress: C-Reactive Protein (CRP) | 6 Months (n=755, 143, 745, 178) | 1.593 milligrams per liter (mg/L) | Standard Error 1.173 |
| Clopidogrel: <75 Years of Age | Biomarker Measurements of Inflammation/Hemodynamic Stress: C-Reactive Protein (CRP) | Day 30 | 2.287 milligrams per liter (mg/L) | Standard Error 1.053 |
| Clopidogrel: <75 Years of Age | Biomarker Measurements of Inflammation/Hemodynamic Stress: C-Reactive Protein (CRP) | 6 Months (n=755, 143, 745, 178) | 2.149 milligrams per liter (mg/L) | Standard Error 1.059 |
| Clopidogrel: 75 Years of Age or Older | Biomarker Measurements of Inflammation/Hemodynamic Stress: C-Reactive Protein (CRP) | 6 Months (n=755, 143, 745, 178) | 1.543 milligrams per liter (mg/L) | Standard Error 1.17 |
| Clopidogrel: 75 Years of Age or Older | Biomarker Measurements of Inflammation/Hemodynamic Stress: C-Reactive Protein (CRP) | Day 30 | 2.226 milligrams per liter (mg/L) | Standard Error 1.15 |
p-value: 0.72795% CI: [0.919, 1.129]ANCOVA
p-value: 0.34695% CI: [0.942, 1.187]ANCOVA
p-value: 0.45895% CI: [0.859, 1.399]ANCOVA
p-value: 0.80295% CI: [0.803, 1.329]ANCOVA
Secondary
Economic and Quality of Life Outcomes
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)
Population: All randomized participants (combined \<75 years and 75 years and older) with SAQ data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Prasugrel: <75 Years of Age | Economic and Quality of Life Outcomes | Baseline, physical limitations | 67.8 units on a scale | Standard Deviation 26.1 |
| Prasugrel: <75 Years of Age | Economic and Quality of Life Outcomes | Baseline, angina frequency | 73.6 units on a scale | Standard Deviation 22.9 |
| Prasugrel: <75 Years of Age | Economic and Quality of Life Outcomes | 24 Months, physical limitations (n=420, 412) | 75.1 units on a scale | Standard Deviation 24.4 |
| Prasugrel: <75 Years of Age | Economic and Quality of Life Outcomes | 24 Months, angina frequency (n=420, 412) | 89.7 units on a scale | Standard Deviation 20 |
| Prasugrel: 75 Years of Age or Older | Economic and Quality of Life Outcomes | 24 Months, angina frequency (n=420, 412) | 89.5 units on a scale | Standard Deviation 19.1 |
| Prasugrel: 75 Years of Age or Older | Economic and Quality of Life Outcomes | Baseline, physical limitations | 67.0 units on a scale | Standard Deviation 26.5 |
| Prasugrel: 75 Years of Age or Older | Economic and Quality of Life Outcomes | 24 Months, physical limitations (n=420, 412) | 74.5 units on a scale | Standard Deviation 25.7 |
| Prasugrel: 75 Years of Age or Older | Economic and Quality of Life Outcomes | Baseline, angina frequency | 73.1 units on a scale | Standard Deviation 23.5 |
p-value: 0.5ANCOVA
p-value: 0.72ANCOVA
p-value: 0.63ANCOVA
p-value: 0.53ANCOVA
Secondary
Genotyping Related to Drug Metabolism
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
Population: All randomized participants who provided a DNA sample.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Prasugrel: <75 Years of Age | Genotyping Related to Drug Metabolism | IM, *1/*8 | 0.1 percentage participants with geneotype |
| Prasugrel: <75 Years of Age | Genotyping Related to Drug Metabolism | UNK, *9/*17 | 0.0 percentage participants with geneotype |
| Prasugrel: <75 Years of Age | Genotyping Related to Drug Metabolism | UNK, Undefined genotype | 0.7 percentage participants with geneotype |
| Prasugrel: <75 Years of Age | Genotyping Related to Drug Metabolism | UNK, *6/*17 | 0.0 percentage participants with geneotype |
| Prasugrel: <75 Years of Age | Genotyping Related to Drug Metabolism | PM, *2/*2 | 3.9 percentage participants with geneotype |
| Prasugrel: <75 Years of Age | Genotyping Related to Drug Metabolism | UNK, *2/*9 | 0.0 percentage participants with geneotype |
| Prasugrel: <75 Years of Age | Genotyping Related to Drug Metabolism | EM (non-UM), *1/*1 | 38.8 percentage participants with geneotype |
| Prasugrel: <75 Years of Age | Genotyping Related to Drug Metabolism | UNK, *2/*13 | 0.0 percentage participants with geneotype |
| Prasugrel: <75 Years of Age | Genotyping Related to Drug Metabolism | PM, *2/*3 | 0.3 percentage participants with geneotype |
| Prasugrel: <75 Years of Age | Genotyping Related to Drug Metabolism | UM, *17/*17 | 5.1 percentage participants with geneotype |
| Prasugrel: <75 Years of Age | Genotyping Related to Drug Metabolism | UNK, *1/*9, *9/*17 | 0.0 percentage participants with geneotype |
| Prasugrel: <75 Years of Age | Genotyping Related to Drug Metabolism | UNK, *4/*9 | 0.0 percentage participants with geneotype |
| Prasugrel: <75 Years of Age | Genotyping Related to Drug Metabolism | PM, *2/*4 | 0.0 percentage participants with geneotype |
| Prasugrel: <75 Years of Age | Genotyping Related to Drug Metabolism | IM, *1/*4 | 0.4 percentage participants with geneotype |
| Prasugrel: <75 Years of Age | Genotyping Related to Drug Metabolism | UM, *1/*17 | 24.0 percentage participants with geneotype |
| Prasugrel: <75 Years of Age | Genotyping Related to Drug Metabolism | UNK, *1/*9 | 0.1 percentage participants with geneotype |
| Prasugrel: <75 Years of Age | Genotyping Related to Drug Metabolism | PM, *2/*6 | 0.0 percentage participants with geneotype |
| Prasugrel: <75 Years of Age | Genotyping Related to Drug Metabolism | IM, *1/*3 | 0.8 percentage participants with geneotype |
| Prasugrel: <75 Years of Age | Genotyping Related to Drug Metabolism | UNK, *8/*17 | 0.2 percentage participants with geneotype |
| Prasugrel: <75 Years of Age | Genotyping Related to Drug Metabolism | UNK, *4/*17 | 0.2 percentage participants with geneotype |
| Prasugrel: <75 Years of Age | Genotyping Related to Drug Metabolism | PM, *2/*8 | 0.0 percentage participants with geneotype |
| Prasugrel: <75 Years of Age | Genotyping Related to Drug Metabolism | IM, *1/*6 | 0.0 percentage participants with geneotype |
| Prasugrel: <75 Years of Age | Genotyping Related to Drug Metabolism | IM, *1/*2 | 18.6 percentage participants with geneotype |
| Prasugrel: <75 Years of Age | Genotyping Related to Drug Metabolism | UNK, *2/*17 | 6.3 percentage participants with geneotype |
| Prasugrel: <75 Years of Age | Genotyping Related to Drug Metabolism | PM, *3/*3 | 0.0 percentage participants with geneotype |
| Prasugrel: <75 Years of Age | Genotyping Related to Drug Metabolism | UNK, *13/*17 | 0.0 percentage participants with geneotype |
| Prasugrel: <75 Years of Age | Genotyping Related to Drug Metabolism | UNK, *1/*13 | 0.0 percentage participants with geneotype |
| Prasugrel: <75 Years of Age | Genotyping Related to Drug Metabolism | UNK, *3/*17 | 0.1 percentage participants with geneotype |
| Prasugrel: <75 Years of Age | Genotyping Related to Drug Metabolism | UNK, *1/*10 | 0.0 percentage participants with geneotype |
| Prasugrel: 75 Years of Age or Older | Genotyping Related to Drug Metabolism | UNK, *4/*9 | 0.0 percentage participants with geneotype |
| Prasugrel: 75 Years of Age or Older | Genotyping Related to Drug Metabolism | UNK, Undefined genotype | 0.6 percentage participants with geneotype |
| Prasugrel: 75 Years of Age or Older | Genotyping Related to Drug Metabolism | UNK, *2/*9 | 0.0 percentage participants with geneotype |
| Prasugrel: 75 Years of Age or Older | Genotyping Related to Drug Metabolism | UNK, *1/*13 | 0.2 percentage participants with geneotype |
| Prasugrel: 75 Years of Age or Older | Genotyping Related to Drug Metabolism | UNK, *1/*9 | 0.2 percentage participants with geneotype |
| Prasugrel: 75 Years of Age or Older | Genotyping Related to Drug Metabolism | UNK, *2/*17 | 6.1 percentage participants with geneotype |
| Prasugrel: 75 Years of Age or Older | Genotyping Related to Drug Metabolism | UNK, *1/*9, *9/*17 | 0.0 percentage participants with geneotype |
| Prasugrel: 75 Years of Age or Older | Genotyping Related to Drug Metabolism | UNK, *13/*17 | 0.0 percentage participants with geneotype |
| Prasugrel: 75 Years of Age or Older | Genotyping Related to Drug Metabolism | IM, *1/*3 | 0.6 percentage participants with geneotype |
| Prasugrel: 75 Years of Age or Older | Genotyping Related to Drug Metabolism | UNK, *2/*13 | 0.0 percentage participants with geneotype |
| Prasugrel: 75 Years of Age or Older | Genotyping Related to Drug Metabolism | UNK, *8/*17 | 0.0 percentage participants with geneotype |
| Prasugrel: 75 Years of Age or Older | Genotyping Related to Drug Metabolism | IM, *1/*4 | 0.0 percentage participants with geneotype |
| Prasugrel: 75 Years of Age or Older | Genotyping Related to Drug Metabolism | UM, *17/*17 | 3.6 percentage participants with geneotype |
| Prasugrel: 75 Years of Age or Older | Genotyping Related to Drug Metabolism | IM, *1/*6 | 0.2 percentage participants with geneotype |
| Prasugrel: 75 Years of Age or Older | Genotyping Related to Drug Metabolism | UM, *1/*17 | 25.0 percentage participants with geneotype |
| Prasugrel: 75 Years of Age or Older | Genotyping Related to Drug Metabolism | UNK, *6/*17 | 0.0 percentage participants with geneotype |
| Prasugrel: 75 Years of Age or Older | Genotyping Related to Drug Metabolism | IM, *1/*8 | 0.5 percentage participants with geneotype |
| Prasugrel: 75 Years of Age or Older | Genotyping Related to Drug Metabolism | PM, *2/*2 | 2.2 percentage participants with geneotype |
| Prasugrel: 75 Years of Age or Older | Genotyping Related to Drug Metabolism | UNK, *1/*10 | 0.0 percentage participants with geneotype |
| Prasugrel: 75 Years of Age or Older | Genotyping Related to Drug Metabolism | PM, *2/*3 | 0.2 percentage participants with geneotype |
| Prasugrel: 75 Years of Age or Older | Genotyping Related to Drug Metabolism | EM (non-UM), *1/*1 | 42.1 percentage participants with geneotype |
| Prasugrel: 75 Years of Age or Older | Genotyping Related to Drug Metabolism | PM, *2/*4 | 0.2 percentage participants with geneotype |
| Prasugrel: 75 Years of Age or Older | Genotyping Related to Drug Metabolism | UNK, *4/*17 | 0.2 percentage participants with geneotype |
| Prasugrel: 75 Years of Age or Older | Genotyping Related to Drug Metabolism | PM, *2/*6 | 0.0 percentage participants with geneotype |
| Prasugrel: 75 Years of Age or Older | Genotyping Related to Drug Metabolism | UNK, *9/*17 | 0.0 percentage participants with geneotype |
| Prasugrel: 75 Years of Age or Older | Genotyping Related to Drug Metabolism | PM, *2/*8 | 0.0 percentage participants with geneotype |
| Prasugrel: 75 Years of Age or Older | Genotyping Related to Drug Metabolism | UNK, *3/*17 | 0.0 percentage participants with geneotype |
| Prasugrel: 75 Years of Age or Older | Genotyping Related to Drug Metabolism | PM, *3/*3 | 0.0 percentage participants with geneotype |
| Prasugrel: 75 Years of Age or Older | Genotyping Related to Drug Metabolism | IM, *1/*2 | 18.3 percentage participants with geneotype |
| Clopidogrel: <75 Years of Age | Genotyping Related to Drug Metabolism | UNK, *1/*13 | 0.0 percentage participants with geneotype |
| Clopidogrel: <75 Years of Age | Genotyping Related to Drug Metabolism | UM, *1/*17 | 25.1 percentage participants with geneotype |
| Clopidogrel: <75 Years of Age | Genotyping Related to Drug Metabolism | UM, *17/*17 | 5.4 percentage participants with geneotype |
| Clopidogrel: <75 Years of Age | Genotyping Related to Drug Metabolism | EM (non-UM), *1/*1 | 35.7 percentage participants with geneotype |
| Clopidogrel: <75 Years of Age | Genotyping Related to Drug Metabolism | IM, *1/*2 | 19.8 percentage participants with geneotype |
| Clopidogrel: <75 Years of Age | Genotyping Related to Drug Metabolism | IM, *1/*3 | 0.5 percentage participants with geneotype |
| Clopidogrel: <75 Years of Age | Genotyping Related to Drug Metabolism | IM, *1/*4 | 0.1 percentage participants with geneotype |
| Clopidogrel: <75 Years of Age | Genotyping Related to Drug Metabolism | IM, *1/*6 | 0.0 percentage participants with geneotype |
| Clopidogrel: <75 Years of Age | Genotyping Related to Drug Metabolism | IM, *1/*8 | 0.4 percentage participants with geneotype |
| Clopidogrel: <75 Years of Age | Genotyping Related to Drug Metabolism | PM, *2/*2 | 4.3 percentage participants with geneotype |
| Clopidogrel: <75 Years of Age | Genotyping Related to Drug Metabolism | PM, *2/*3 | 0.3 percentage participants with geneotype |
| Clopidogrel: <75 Years of Age | Genotyping Related to Drug Metabolism | PM, *2/*4 | 0.2 percentage participants with geneotype |
| Clopidogrel: <75 Years of Age | Genotyping Related to Drug Metabolism | PM, *2/*6 | 0.0 percentage participants with geneotype |
| Clopidogrel: <75 Years of Age | Genotyping Related to Drug Metabolism | PM, *2/*8 | 0.0 percentage participants with geneotype |
| Clopidogrel: <75 Years of Age | Genotyping Related to Drug Metabolism | PM, *3/*3 | 0.2 percentage participants with geneotype |
| Clopidogrel: <75 Years of Age | Genotyping Related to Drug Metabolism | UNK, *1/*10 | 0.1 percentage participants with geneotype |
| Clopidogrel: <75 Years of Age | Genotyping Related to Drug Metabolism | UNK, *1/*9 | 0.0 percentage participants with geneotype |
| Clopidogrel: <75 Years of Age | Genotyping Related to Drug Metabolism | UNK, *1/*9, *9/*17 | 0.0 percentage participants with geneotype |
| Clopidogrel: <75 Years of Age | Genotyping Related to Drug Metabolism | UNK, *13/*17 | 0.0 percentage participants with geneotype |
| Clopidogrel: <75 Years of Age | Genotyping Related to Drug Metabolism | UNK, *2/*13 | 0.0 percentage participants with geneotype |
| Clopidogrel: <75 Years of Age | Genotyping Related to Drug Metabolism | UNK, *2/*17 | 6.8 percentage participants with geneotype |
| Clopidogrel: <75 Years of Age | Genotyping Related to Drug Metabolism | UNK, *2/*9 | 0.1 percentage participants with geneotype |
| Clopidogrel: <75 Years of Age | Genotyping Related to Drug Metabolism | UNK, *3/*17 | 0.0 percentage participants with geneotype |
| Clopidogrel: <75 Years of Age | Genotyping Related to Drug Metabolism | UNK, *4/*17 | 0.2 percentage participants with geneotype |
| Clopidogrel: <75 Years of Age | Genotyping Related to Drug Metabolism | UNK, *4/*9 | 0.0 percentage participants with geneotype |
| Clopidogrel: <75 Years of Age | Genotyping Related to Drug Metabolism | UNK, *6/*17 | 0.0 percentage participants with geneotype |
| Clopidogrel: <75 Years of Age | Genotyping Related to Drug Metabolism | UNK, *8/*17 | 0.1 percentage participants with geneotype |
| Clopidogrel: <75 Years of Age | Genotyping Related to Drug Metabolism | UNK, *9/*17 | 0.0 percentage participants with geneotype |
| Clopidogrel: <75 Years of Age | Genotyping Related to Drug Metabolism | UNK, Undefined genotype | 0.5 percentage participants with geneotype |
| Clopidogrel: 75 Years of Age or Older | Genotyping Related to Drug Metabolism | UNK, *2/*9 | 0.0 percentage participants with geneotype |
| Clopidogrel: 75 Years of Age or Older | Genotyping Related to Drug Metabolism | PM, *3/*3 | 0.0 percentage participants with geneotype |
| Clopidogrel: 75 Years of Age or Older | Genotyping Related to Drug Metabolism | PM, *2/*8 | 0.0 percentage participants with geneotype |
| Clopidogrel: 75 Years of Age or Older | Genotyping Related to Drug Metabolism | EM (non-UM), *1/*1 | 41.2 percentage participants with geneotype |
| Clopidogrel: 75 Years of Age or Older | Genotyping Related to Drug Metabolism | UNK, *3/*17 | 0.3 percentage participants with geneotype |
| Clopidogrel: 75 Years of Age or Older | Genotyping Related to Drug Metabolism | PM, *2/*6 | 0.0 percentage participants with geneotype |
| Clopidogrel: 75 Years of Age or Older | Genotyping Related to Drug Metabolism | PM, *2/*4 | 0.2 percentage participants with geneotype |
| Clopidogrel: 75 Years of Age or Older | Genotyping Related to Drug Metabolism | UNK, Undefined genotype | 0.6 percentage participants with geneotype |
| Clopidogrel: 75 Years of Age or Older | Genotyping Related to Drug Metabolism | UNK, *4/*17 | 0.0 percentage participants with geneotype |
| Clopidogrel: 75 Years of Age or Older | Genotyping Related to Drug Metabolism | PM, *2/*3 | 0.3 percentage participants with geneotype |
| Clopidogrel: 75 Years of Age or Older | Genotyping Related to Drug Metabolism | PM, *2/*2 | 3.8 percentage participants with geneotype |
| Clopidogrel: 75 Years of Age or Older | Genotyping Related to Drug Metabolism | UNK, *9/*17 | 0.0 percentage participants with geneotype |
| Clopidogrel: 75 Years of Age or Older | Genotyping Related to Drug Metabolism | UNK, *4/*9 | 0.0 percentage participants with geneotype |
| Clopidogrel: 75 Years of Age or Older | Genotyping Related to Drug Metabolism | IM, *1/*8 | 0.3 percentage participants with geneotype |
| Clopidogrel: 75 Years of Age or Older | Genotyping Related to Drug Metabolism | IM, *1/*6 | 0.2 percentage participants with geneotype |
| Clopidogrel: 75 Years of Age or Older | Genotyping Related to Drug Metabolism | UM, *17/*17 | 4.3 percentage participants with geneotype |
| Clopidogrel: 75 Years of Age or Older | Genotyping Related to Drug Metabolism | UNK, *6/*17 | 0.2 percentage participants with geneotype |
| Clopidogrel: 75 Years of Age or Older | Genotyping Related to Drug Metabolism | IM, *1/*4 | 0.3 percentage participants with geneotype |
| Clopidogrel: 75 Years of Age or Older | Genotyping Related to Drug Metabolism | IM, *1/*3 | 0.6 percentage participants with geneotype |
| Clopidogrel: 75 Years of Age or Older | Genotyping Related to Drug Metabolism | UNK, *13/*17 | 0.0 percentage participants with geneotype |
| Clopidogrel: 75 Years of Age or Older | Genotyping Related to Drug Metabolism | UM, *1/*17 | 21.8 percentage participants with geneotype |
| Clopidogrel: 75 Years of Age or Older | Genotyping Related to Drug Metabolism | UNK, *2/*13 | 0.0 percentage participants with geneotype |
| Clopidogrel: 75 Years of Age or Older | Genotyping Related to Drug Metabolism | UNK, *1/*9, *9/*17 | 0.0 percentage participants with geneotype |
| Clopidogrel: 75 Years of Age or Older | Genotyping Related to Drug Metabolism | UNK, *1/*9 | 0.0 percentage participants with geneotype |
| Clopidogrel: 75 Years of Age or Older | Genotyping Related to Drug Metabolism | UNK, *8/*17 | 0.0 percentage participants with geneotype |
| Clopidogrel: 75 Years of Age or Older | Genotyping Related to Drug Metabolism | UNK, *2/*17 | 6.2 percentage participants with geneotype |
| Clopidogrel: 75 Years of Age or Older | Genotyping Related to Drug Metabolism | UNK, *1/*13 | 0.0 percentage participants with geneotype |
| Clopidogrel: 75 Years of Age or Older | Genotyping Related to Drug Metabolism | UNK, *1/*10 | 0.0 percentage participants with geneotype |
| Clopidogrel: 75 Years of Age or Older | Genotyping Related to Drug Metabolism | IM, *1/*2 | 19.7 percentage participants with geneotype |
Secondary
Percentage of Participants With a Composite Endpoint of All-cause Death, MI, or Stroke
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)
Population: All randomized participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Prasugrel: <75 Years of Age | Percentage of Participants With a Composite Endpoint of All-cause Death, MI, or Stroke | 10.61 percentage of participants with an event |
| Prasugrel: 75 Years of Age or Older | Percentage of Participants With a Composite Endpoint of All-cause Death, MI, or Stroke | 27.04 percentage of participants with an event |
| Clopidogrel: <75 Years of Age | Percentage of Participants With a Composite Endpoint of All-cause Death, MI, or Stroke | 11.12 percentage of participants with an event |
| Clopidogrel: 75 Years of Age or Older | Percentage of Participants With a Composite Endpoint of All-cause Death, MI, or Stroke | 26.83 percentage of participants with an event |
p-value: 0.2795% CI: [0.81, 1.063]Log Rank
p-value: 0.83195% CI: [0.862, 1.2]Log Rank
Secondary
Percentage of Participants With a Composite Endpoint of CV Death and MI
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)
Population: All randomized participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Prasugrel: <75 Years of Age | Percentage of Participants With a Composite Endpoint of CV Death and MI | 9.61 percentage of participants with an event |
| Prasugrel: 75 Years of Age or Older | Percentage of Participants With a Composite Endpoint of CV Death and MI | 22.53 percentage of participants with an event |
| Clopidogrel: <75 Years of Age | Percentage of Participants With a Composite Endpoint of CV Death and MI | 10.21 percentage of participants with an event |
| Clopidogrel: 75 Years of Age or Older | Percentage of Participants With a Composite Endpoint of CV Death and MI | 22.69 percentage of participants with an event |
p-value: 0.38895% CI: [0.812, 1.088]Log Rank
p-value: 0.9995% CI: [0.833, 1.195]Log Rank
Secondary
Percentage of Participants With a Composite Endpoint of CV Death, MI, Stroke, or Re-hospitalization for Recurrent Unstable Angina (UA)
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)
Population: All randomized participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Prasugrel: <75 Years of Age | Percentage of Participants With a Composite Endpoint of CV Death, MI, Stroke, or Re-hospitalization for Recurrent Unstable Angina (UA) | 12.13 percentage of participants with an event |
| Prasugrel: 75 Years of Age or Older | Percentage of Participants With a Composite Endpoint of CV Death, MI, Stroke, or Re-hospitalization for Recurrent Unstable Angina (UA) | 26.27 percentage of participants with an event |
| Clopidogrel: <75 Years of Age | Percentage of Participants With a Composite Endpoint of CV Death, MI, Stroke, or Re-hospitalization for Recurrent Unstable Angina (UA) | 12.83 percentage of participants with an event |
| Clopidogrel: 75 Years of Age or Older | Percentage of Participants With a Composite Endpoint of CV Death, MI, Stroke, or Re-hospitalization for Recurrent Unstable Angina (UA) | 25.67 percentage of participants with an event |
p-value: 0.35395% CI: [0.826, 1.073]Log Rank
p-value: 0.71995% CI: [0.869, 1.218]Log Rank
Secondary
Platelet Aggregation Measures
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
Population: 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 | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Prasugrel: <75 Years of Age | Platelet Aggregation Measures | Day 30 | 93.280 P2Y12 Reaction Units (PRU) | Standard Error 3.804 |
| Prasugrel: <75 Years of Age | Platelet Aggregation Measures | Month 12 (n=386, 76, 400, 103) | 94.529 P2Y12 Reaction Units (PRU) | Standard Error 5.706 |
| Prasugrel: 75 Years of Age or Older | Platelet Aggregation Measures | Month 12 (n=386, 76, 400, 103) | 135.096 P2Y12 Reaction Units (PRU) | Standard Error 14.631 |
| Prasugrel: 75 Years of Age or Older | Platelet Aggregation Measures | Day 30 | 151.872 P2Y12 Reaction Units (PRU) | Standard Error 8.148 |
| Clopidogrel: <75 Years of Age | Platelet Aggregation Measures | Day 30 | 193.489 P2Y12 Reaction Units (PRU) | Standard Error 3.78 |
| Clopidogrel: <75 Years of Age | Platelet Aggregation Measures | Month 12 (n=386, 76, 400, 103) | 199.003 P2Y12 Reaction Units (PRU) | Standard Error 5.663 |
| Clopidogrel: 75 Years of Age or Older | Platelet Aggregation Measures | Day 30 | 200.285 P2Y12 Reaction Units (PRU) | Standard Error 8.238 |
| Clopidogrel: 75 Years of Age or Older | Platelet Aggregation Measures | Month 12 (n=386, 76, 400, 103) | 181.360 P2Y12 Reaction Units (PRU) | Standard Error 14.38 |
p-value: <0.00195% CI: [-107.872, -92.545]ANCOVA
p-value: <0.00195% CI: [-115.383, -93.566]ANCOVA
p-value: <0.00195% CI: [-63.718, -33.108]ANCOVA
p-value: <0.00195% CI: [-69.061, -23.468]ANCOVA
Secondary
Summary of All Deaths
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)
Population: All randomized participants
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Prasugrel: <75 Years of Age | Summary of All Deaths | Congestive Heart Failure | 10 participants |
| Prasugrel: <75 Years of Age | Summary of All Deaths | Sudden death due to cardiovascular event | 75 participants |
| Prasugrel: <75 Years of Age | Summary of All Deaths | Non-Hemorrhagic Stroke | 4 participants |
| Prasugrel: <75 Years of Age | Summary of All Deaths | Stent Thrombosis | 0 participants |
| Prasugrel: <75 Years of Age | Summary of All Deaths | Cause unknown (nonadjudicated event) | 0 participants |
| Prasugrel: <75 Years of Age | Summary of All Deaths | Intracranial Hemorrhage | 2 participants |
| Prasugrel: <75 Years of Age | Summary of All Deaths | Directly Related to Revascularization-CABG or PCI | 1 participants |
| Prasugrel: <75 Years of Age | Summary of All Deaths | Malignancy | 14 participants |
| Prasugrel: <75 Years of Age | Summary of All Deaths | Infection | 14 participants |
| Prasugrel: <75 Years of Age | Summary of All Deaths | Cardiogenic Shock | 8 participants |
| Prasugrel: <75 Years of Age | Summary of All Deaths | Accidental | 1 participants |
| Prasugrel: <75 Years of Age | Summary of All Deaths | Hemorrhage, not intracranial | 1 participants |
| Prasugrel: <75 Years of Age | Summary of All Deaths | Trauma | 2 participants |
| Prasugrel: <75 Years of Age | Summary of All Deaths | Cardiac Rupture | 0 participants |
| Prasugrel: <75 Years of Age | Summary of All Deaths | Other Non-Cardiovascular event | 8 participants |
| Prasugrel: <75 Years of Age | Summary of All Deaths | Cardiovascular event, unknown type | 40 participants |
| Prasugrel: <75 Years of Age | Summary of All Deaths | Other Cardiovascular Event | 6 participants |
| Prasugrel: <75 Years of Age | Summary of All Deaths | Myocardial Infarction | 16 participants |
| Prasugrel: <75 Years of Age | Summary of All Deaths | Suicide | 1 participants |
| Prasugrel: <75 Years of Age | Summary of All Deaths | Stroke, unknown type | 0 participants |
| Prasugrel: <75 Years of Age | Summary of All Deaths | Pulmonary Embolism | 0 participants |
| Prasugrel: <75 Years of Age | Summary of All Deaths | Dysrhythmia | 5 participants |
| Prasugrel: 75 Years of Age or Older | Summary of All Deaths | Hemorrhage, not intracranial | 1 participants |
| Prasugrel: 75 Years of Age or Older | Summary of All Deaths | Congestive Heart Failure | 21 participants |
| Prasugrel: 75 Years of Age or Older | Summary of All Deaths | Cardiogenic Shock | 4 participants |
| Prasugrel: 75 Years of Age or Older | Summary of All Deaths | Cardiac Rupture | 1 participants |
| Prasugrel: 75 Years of Age or Older | Summary of All Deaths | Myocardial Infarction | 24 participants |
| Prasugrel: 75 Years of Age or Older | Summary of All Deaths | Dysrhythmia | 2 participants |
| Prasugrel: 75 Years of Age or Older | Summary of All Deaths | Stent Thrombosis | 0 participants |
| Prasugrel: 75 Years of Age or Older | Summary of All Deaths | Directly Related to Revascularization-CABG or PCI | 1 participants |
| Prasugrel: 75 Years of Age or Older | Summary of All Deaths | Intracranial Hemorrhage | 1 participants |
| Prasugrel: 75 Years of Age or Older | Summary of All Deaths | Non-Hemorrhagic Stroke | 4 participants |
| Prasugrel: 75 Years of Age or Older | Summary of All Deaths | Sudden death due to cardiovascular event | 39 participants |
| Prasugrel: 75 Years of Age or Older | Summary of All Deaths | Pulmonary Embolism | 1 participants |
| Prasugrel: 75 Years of Age or Older | Summary of All Deaths | Stroke, unknown type | 1 participants |
| Prasugrel: 75 Years of Age or Older | Summary of All Deaths | Other Cardiovascular Event | 1 participants |
| Prasugrel: 75 Years of Age or Older | Summary of All Deaths | Cardiovascular event, unknown type | 41 participants |
| Prasugrel: 75 Years of Age or Older | Summary of All Deaths | Trauma | 3 participants |
| Prasugrel: 75 Years of Age or Older | Summary of All Deaths | Accidental | 0 participants |
| Prasugrel: 75 Years of Age or Older | Summary of All Deaths | Infection | 21 participants |
| Prasugrel: 75 Years of Age or Older | Summary of All Deaths | Malignancy | 7 participants |
| Prasugrel: 75 Years of Age or Older | Summary of All Deaths | Suicide | 0 participants |
| Prasugrel: 75 Years of Age or Older | Summary of All Deaths | Other Non-Cardiovascular event | 4 participants |
| Prasugrel: 75 Years of Age or Older | Summary of All Deaths | Cause unknown (nonadjudicated event) | 1 participants |
| Clopidogrel: <75 Years of Age | Summary of All Deaths | Malignancy | 14 participants |
| Clopidogrel: <75 Years of Age | Summary of All Deaths | Pulmonary Embolism | 2 participants |
| Clopidogrel: <75 Years of Age | Summary of All Deaths | Myocardial Infarction | 24 participants |
| Clopidogrel: <75 Years of Age | Summary of All Deaths | Suicide | 0 participants |
| Clopidogrel: <75 Years of Age | Summary of All Deaths | Stroke, unknown type | 0 participants |
| Clopidogrel: <75 Years of Age | Summary of All Deaths | Other Cardiovascular Event | 0 participants |
| Clopidogrel: <75 Years of Age | Summary of All Deaths | Cardiac Rupture | 0 participants |
| Clopidogrel: <75 Years of Age | Summary of All Deaths | Cardiovascular event, unknown type | 45 participants |
| Clopidogrel: <75 Years of Age | Summary of All Deaths | Cause unknown (nonadjudicated event) | 0 participants |
| Clopidogrel: <75 Years of Age | Summary of All Deaths | Trauma | 0 participants |
| Clopidogrel: <75 Years of Age | Summary of All Deaths | Cardiogenic Shock | 10 participants |
| Clopidogrel: <75 Years of Age | Summary of All Deaths | Other Non-Cardiovascular event | 8 participants |
| Clopidogrel: <75 Years of Age | Summary of All Deaths | Hemorrhage, not intracranial | 0 participants |
| Clopidogrel: <75 Years of Age | Summary of All Deaths | Infection | 16 participants |
| Clopidogrel: <75 Years of Age | Summary of All Deaths | Congestive Heart Failure | 13 participants |
| Clopidogrel: <75 Years of Age | Summary of All Deaths | Accidental | 1 participants |
| Clopidogrel: <75 Years of Age | Summary of All Deaths | Stent Thrombosis | 0 participants |
| Clopidogrel: <75 Years of Age | Summary of All Deaths | Intracranial Hemorrhage | 4 participants |
| Clopidogrel: <75 Years of Age | Summary of All Deaths | Non-Hemorrhagic Stroke | 4 participants |
| Clopidogrel: <75 Years of Age | Summary of All Deaths | Dysrhythmia | 6 participants |
| Clopidogrel: <75 Years of Age | Summary of All Deaths | Directly Related to Revascularization-CABG or PCI | 1 participants |
| Clopidogrel: <75 Years of Age | Summary of All Deaths | Sudden death due to cardiovascular event | 70 participants |
| Clopidogrel: 75 Years of Age or Older | Summary of All Deaths | Non-Hemorrhagic Stroke | 3 participants |
| Clopidogrel: 75 Years of Age or Older | Summary of All Deaths | Cause unknown (nonadjudicated event) | 0 participants |
| Clopidogrel: 75 Years of Age or Older | Summary of All Deaths | Hemorrhage, not intracranial | 4 participants |
| Clopidogrel: 75 Years of Age or Older | Summary of All Deaths | Pulmonary Embolism | 1 participants |
| Clopidogrel: 75 Years of Age or Older | Summary of All Deaths | Congestive Heart Failure | 23 participants |
| Clopidogrel: 75 Years of Age or Older | Summary of All Deaths | Other Non-Cardiovascular event | 6 participants |
| Clopidogrel: 75 Years of Age or Older | Summary of All Deaths | Intracranial Hemorrhage | 1 participants |
| Clopidogrel: 75 Years of Age or Older | Summary of All Deaths | Stroke, unknown type | 0 participants |
| Clopidogrel: 75 Years of Age or Older | Summary of All Deaths | Cardiac Rupture | 0 participants |
| Clopidogrel: 75 Years of Age or Older | Summary of All Deaths | Suicide | 0 participants |
| Clopidogrel: 75 Years of Age or Older | Summary of All Deaths | Infection | 17 participants |
| Clopidogrel: 75 Years of Age or Older | Summary of All Deaths | Other Cardiovascular Event | 1 participants |
| Clopidogrel: 75 Years of Age or Older | Summary of All Deaths | Dysrhythmia | 3 participants |
| Clopidogrel: 75 Years of Age or Older | Summary of All Deaths | Accidental | 1 participants |
| Clopidogrel: 75 Years of Age or Older | Summary of All Deaths | Stent Thrombosis | 0 participants |
| Clopidogrel: 75 Years of Age or Older | Summary of All Deaths | Cardiovascular event, unknown type | 45 participants |
| Clopidogrel: 75 Years of Age or Older | Summary of All Deaths | Cardiogenic Shock | 9 participants |
| Clopidogrel: 75 Years of Age or Older | Summary of All Deaths | Malignancy | 11 participants |
| Clopidogrel: 75 Years of Age or Older | Summary of All Deaths | Directly Related to Revascularization-CABG or PCI | 1 participants |
| Clopidogrel: 75 Years of Age or Older | Summary of All Deaths | Trauma | 1 participants |
| Clopidogrel: 75 Years of Age or Older | Summary of All Deaths | Sudden death due to cardiovascular event | 43 participants |
| Clopidogrel: 75 Years of Age or Older | Summary of All Deaths | Myocardial Infarction | 21 participants |