Adverse outcomes after primary percutaneous coronary intervention (PCI) for patients with ST-segment elevation myocardial infarction (STEMI) are less frequent with prasugrel (Effient) than with other drugs in the P2Y 12 antagonist class, a meta-analysis suggested. At 1 month, the evidence tipped toward fewer major adverse cardiovascular events (MACE) with prasugrel than clopidogrel (standard dose odds ratio 0.59, 95% CI 0.50- 0.69) or ticagrelor (standard dose OR 0.69, 95% CI 0.56-0.84), according to Timothy D. Henry, MD, of Cedars-Sinai Heart Institute in Los Angeles, and colleagues writing in JACC: Cardiovascular Interventions. Stroke rates were also lower with prasugrel versus clopidogrel (standard dose OR 0.36, 95% CI 0.17-0.70) as were rates of stent thrombosis (standard dose OR 0.48, 95% CI 0.30-0.78). Stroke, but not stent thrombosis, was also more likely with ticagrelor over prasugrel (standard dose OR 0.30, 95% CI 0.18-0.58). One year after PCI, prasugrel was the P2Y 12 inhibitor associated with the fewest deaths and MACE, the difference especially pronounced when patients also got bivalirudin and drug-eluting stents. What’s more, as was seen in earlier analyses, rates of bleeding were similar between P2Y 12 inhibitors. “Our study highlights the need for a randomized clinical trial to compare various P2Y 12 inhibitors in STEMI patients,” the investigators concluded. The meta-analysis included 37 studies with a total of 88,402 patients. Yet in an accompanying editorial, William Wijns, MD, PhD, of Belgium’s Cardiovascular Research Center Aalst, and colleagues suggested that the evidence currently in hand may be sufficient for choosing among the P2Y 12 antagonists. “It seems unlikely that a large enough dedicated comparative randomized trial will ever be performed, for two important reasons: funding of such a trial will be difficult, and, most important, today, identifying a winner among oral antiplatelet drugs with delayed onset of action, be it prasugrel or ticagrelor, is no longer a major, clinically relevant issue,” Wijns and colleagues wrote. Given the hours required for oral agents to take effect, they noted, “intravenous compounds may be even more effective in bridging patients to the full effect of oral antiplatelet agents.” Instead of comparing P2Y 12 inhibitors, the editorialists called for trials investigating a strategy of using both intravenous and oral agents. “In patients with acute thrombotic events, use of an antiplatelet agent with a fast onset of action, a predictable effect, and a fast offset is the best option, which will be provided by an intravenously administered drug,” Wijns and colleagues wrote. “During primary PCI for STEMI and the early in-hospital phase, the intravenous drug will cover the gap in platelet inhibition before the full effect of the oral drug.” “As to improving long-term prognosis, the intensity and duration of oral antiplatelet therapy will be tailored to each patient’s need, balancing ischemic and bleeding risks,” they suggested. Disclosures Henry disclosed serving on steering committes for TRANSLATE (sponsored by Eli Lily and Daiichi-Sankyo) and Artemis (supported by AstraZeneca). Wijns reported receiving institutional grant funding from Medtronic, Boston Scientific, Terumo, MiCell, Microport, St. Jude Medical, Stentys, AstraZeneca, Biotronik, and Abbott Vascular; and serving as a non-executive board member and shareholder of Argonauts Partners, Celyad, and Genae.