• Risk of the composite endpoint of first occurence of CV death and MI. [ Time Frame: Randomization through end of study (minimum of 6-month follow-up period). ] [ Designated as safety issue: Yes ]
• Risk of the composite endpoint of first occurrence CV death, MI, stroke, or re-hospitalization for recurrent UA. [ Time Frame: Randomization through end of study (minimum of 6-month follow-up period). ] [ Designated as safety issue: Yes ]
• Risk of the composite endpoint of first occurrence of all-cause death, MI, or stroke. [ Time Frame: Randomization through end of study (minimum of 6-month follow-up period). ] [ Designated as safety issue: Yes ]
• Platelet aggregation measures. [ Time Frame: Baseline and at various timepoints during study treatment. ] [ Designated as safety issue: No ]
• Biomarker measurements of inflammation/hemodynamic stress. [ Time Frame: Baseline and at various timepoints during study treatment. ] [ Designated as safety issue: No ]
• Genotyping related to drug metabolism. [ Time Frame: Baseline ] [ Designated as safety issue: No ]
• Economic and Quality of Life Outcomes. [ Time Frame: Baseline, follow-up, and discontinuation from study. ] [ Designated as safety issue: No ]

This study will evaluate the relative efficacy and safety of prasugrel and clopidogrel in a medically managed UA/NSTEMI ACS population (that is, patients who are not managed with acute coronary revascularization).

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 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.

• Drug: Clopidogrel
• Drug: Prasugrel
• Drug: Commercially-available Aspirin

• Experimental: Prasugrel and Low-dose Commercially-available Aspirin
• Active Comparator: Clopidogrel and Low-Dose Commercially-available Aspirin

Key Inclusion Criteria:

• Have had a UA/NSTEMI index event within 7 days prior to randomization
• Had a medical management strategy decision made with reasonable certainty that neither PCI nor CABG is planned for treatment of the index events
• Had at least 1 of 3 specified high-risk features at the time of the UA/NSTEMI event
• Have at least 1 native coronary artery stenosis greater than 50% (if diagnostic coronary angiography performed during the index event hospitalization).

Key Exclusion Criteria:

• Decision for medical management greater than 24 hours after onset of index event without commercial clopidogrel treatment within 24 hours following onset of the index event.
• Previous or planned PCI or CABG as treatment for the index event
• PCI or CABG within the previous 30 days
• STEMI as the index event
• Cardiogenic shock, Refractory ventricular arrhythmias, NYHA Class IV CHF within the previous 24 hours
• History of ischemic or hemorrhagic stroke, TIA, Intracranial neoplasm, arteriovenous malformation, or aneurysm
• History of spontaneous GI or non-GI internal bleeding requiring in-hospital treatment
• Hemodialysis or peritoneal dialysis

• Daiichi Sankyo Co., Ltd.
• DCRI