• Gilles Montalescot, Leonardo Bolognese, Dariusz Dudek, Patrick Goldstein, Christian Hamm, Jean-Francois Tanguay, Jurrien M ten Berg, Debra L Miller, Timothy M Costigan, Jochen Goedicke, Johanne Silvain, Paolo Angioli, Jacek Legutko, Margit Niethammer, Zuzana Motovska, Joseph A Jakubowski, Guillaume Cayla, Luigi Oltrona Visconti, Eric Vicaut, Petr Widimsky, and ACCOAST Investigators.
• Institut de Cardiologie, Centre Hospitalier Universitaire Pitié–Salpêtrière (ACTION group, Assistance Publique–Hôpitaux de Paris [AP-HP], Université Paris 6), Paris, France. gilles.montalescot@psl.aphp.fr
• N. Engl. J. Med.. 2013 Sep 12;369(11):999-1010.

BackgroundAlthough P2Y12 antagonists are effective in patients with non-ST-segment elevation (NSTE) acute coronary syndromes, the effect of the timing of administration--before or after coronary angiography--is not known. We evaluated the effect of administering the P2Y12 antagonist prasugrel at the time of diagnosis versus administering it after the coronary angiography if percutaneous coronary intervention (PCI) was indicated.MethodsWe enrolled 4033 patients with NSTE acute coronary syndromes and a positive troponin level who were scheduled to undergo coronary angiography within 2 to 48 hours after randomization. Patients were randomly assigned to receive prasugrel (a 30-mg loading dose) before the angiography (pretreatment group) or placebo (control group). When PCI was indicated, an additional 30 mg of prasugrel was given in the pretreatment group at the time of PCI and 60 mg of prasugrel was given in the control group.ResultsThe rate of the primary efficacy end point, a composite of death from cardiovascular causes, myocardial infarction, stroke, urgent revascularization, or glycoprotein IIb/IIIa inhibitor rescue therapy (glycoprotein IIb/IIIa bailout) through day 7, did not differ significantly between the two groups (hazard ratio with pretreatment, 1.02; 95% confidence interval [CI], 0.84 to 1.25; P=0.81). The rate of the key safety end point of all Thrombolysis in Myocardial Infarction (TIMI) major bleeding episodes, whether related or not related to coronary-artery bypass grafting (CABG), through day 7 was increased with pretreatment (hazard ratio, 1.90; 95% CI, 1.19 to 3.02; P=0.006). The rates of TIMI major bleeding and life-threatening bleeding not related to CABG were increased by a factor of 3 and 6, respectively. Pretreatment did not reduce the rate of the primary outcome among patients undergoing PCI (69% of the patients) but increased the rate of TIMI major bleeding at 7 days. All the results were confirmed at 30 days and in prespecified subgroups.ConclusionsAmong patients with NSTE acute coronary syndromes who were scheduled to undergo catheterization, pretreatment with prasugrel did not reduce the rate of major ischemic events up to 30 days but increased the rate of major bleeding complications. (Funded by Daiichi Sankyo and Eli Lilly; ACCOAST ClinicalTrials.gov number, NCT01015287.).

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