This was driven by a risk reduction for MI and stent thrombosis with no differ- ence in mortality.302 Counterbalancing the salutary effects of prasugrel was a significant increase in spontaneous bleeding, life-threatening bleeding, and fatal bleeding in the patients treated with prasugrel compared with patients treated with clopidogrel. There was net harm in patients with a history of cerebrovascular events and no clinical benefit in patients >75 years of age or those with low body weight (<60 kg).302 In patients with NSTE-ACS treated with an ischemia-guided strategy, 1 RCT comparing aspirin and either clopidogrel or prasugrel evaluated the primary endpoint of death from car- diovascular causes, MI, or stroke for up to 30 months; there were similar bleeding rates and no benefit of treatment with prasugrel when compared with treatment with clopidogrel.303 The ACCOAST (A Comparison of Prasugrel at the Time of Percutaneous Coronary Intervention or as Pretreatment at the Time of Diagnosis in Patients With Non ST-Elevation Myocardial Infarction) RCT of high-risk patients with NSTE- ACS scheduled to undergo early coronary angiography found that a strategy of administration of prasugrel at the time of randomization before angiography did not lead to a reduc- tion in the composite primary endpoint when compared with a strategy of administration of prasugrel only at the time of PCI; however, it did lead to an increase in bleeding complica- On the basis of TRITON (Trial toAssess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel) study design and the results of TRILOGY ACS (Targeted Platelet Inhibition to Clarify the Optimal Strategy to Medically Manage Acute Coronary Syndromes) and ACCOAST, prasugrel is not recommended for upfront therapy in patients with NSTE-ACS. The use of prasugrel in patients undergoing PCI is addressed in Section 5. 