Prasugrel in the Poststroke Cohort of the TRITON Trial: The Clear and Present Danger

dogrel [1] . Patients with moderateto high-risk acute coronary syndromes with the defined coronary anatomy and planned stent placement were randomized to prasugrel or clopidogrel for 6–15 months. The primary endpoint was the time to the first event of cardiovascular death, myocardial infarction or stroke, and occurred in 12.1% of patients treated with clopidogrel and 9.9% of patients randomized to prasugrel (for details, see table 1 ). This difference favoring prasugrel was predominantly attributed to the early decrease in ischemic episodes during the first 3 days after intervention [2] . Analysis of the individual components of the combined efficacy endpoint suggests that the difference between the two treatment arms was exclusively driven by the rates of nonfatal myocardial infarction (475 vs. 620 events) favoring prasugrel. In contrast, mortality was identical (prasugrel – 154; clopidogrel – 155), when for each cardiovascular death prevented by prasugrel versus clopidogrel (133/150), one additional fatal bleeding event (21/5) occurred in the prasugrel group [3] . There was no difference in stroke prevention (prasugrel – 61; clopidogrel – 60). The excess bleeding risk after prasugrel is not surprising because the antiplatelet potency of the prasugrel loading and maintenance dose chosen for TRITON was about 2.5 times more potent than the clopidogrel regimen [4] . Exploratory post hoc analyses of the TRITON data set revealed a lack of benefit, and even harm, for patients with previous ischemic stroke and transient ischemic attack (TIA) who received prasugrel compared to clopidogrel. Considering that hemorrhagic stroke was one of the exclusion criteria, there were 518 patients in TRITON with the history of ischemic stroke or TIA, which were equally distributed between the prasugrel (n = 262) and clopidogrel (n = 256) cohorts. The outcome and safety measured in patients with previous cerebrovascular ischemic events are summarized in table 2 . The Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel Thrombolysis in Myocardial Infarction 38 (TRITON-TIMI 38) was an important phase 3, randomized study. The trial assessed head-to-head the efficacy and safety of the experimental thienopyridine prasugrel versus standard care with another P2Y12 platelet inhibitor, clopiPublished online: June 12, 2008