• Monica Verdoia, Alon Schaffer, Lucia Barbieri, Ettore Cassetti, Raffaele Piccolo, Gennaro Galasso, Paolo Marino, Fabiola Sinigaglia, and Giuseppe De Luca.
• *Division of Cardiology, Azienda Ospedaliera-Universitaria "Maggiore della Carità," Eastern Piedmont University, Novara, Italy; †Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy; and ‡Department of Translational Medicine, Centro di Biotecnologie per la Ricerca Medica Applicata (BRMA), Eastern Piedmont University, Novara, Italy.
• J. Cardiovasc. Pharmacol. 2014 Apr 1; 63 (4): 339-50.

AimsNew P2Y12 receptor inhibitors have provided new and more potent antiplatelet strategies, although raising several concerns on possible increase of bleedings. The aim of current meta-analysis was to evaluate the efficacy and safety of new adenosine diphosphate (ADP) receptor antagonists as compared with clopidogrel in elective or ACS patients managed invasively.Methods And ResultsLiterature archives (Pubmed, EMBASE, Cochrane) and main scientific sessions abstracts were scanned for randomized trials comparing new ADP antagonists with clopidogrel in patients with acute coronary syndromes or stable angina. Primary endpoint was mortality. Secondary endpoints were: (1) nonfatal myocardial infarction (MI), (2) recurrent ischemia symptoms or ischemia-driven revascularization (RI/IDR), (3) stent thrombosis (ST), and (4) safety endpoints, defined as for TIMI major bleeding criteria. A total of 8 randomized clinical trials were finally included, for a total population of 67,851 patients. Mean follow-up was 7.6 months, ranging from 48 hours to 30 months. New ADP antagonists significantly reduced mortality {3.1% vs. 3.6%, odds ratio [OR] [95% confidence interval (CI)], 0.86 [0.79-0.94], P = 0.0008, P(het) = 0.18}, with greater impact of oral drugs. Similar benefits were found for MI [6.1% vs. 7%; OR (95% CI) (random-effect model) = 0.88 (0.79-0.98), P = 0.01, P(het) = 0.02], RI [2.7% vs. 3.1%; OR (95% CI) = 0.85 (0.77-0.93), P = 0.0005, P(het) = 0.09], or ST [1.1% vs. 1.7%; OR (95% CI) = 0.60 (0.51-0.71), P < 0.00001, P(het) = 0.13]. By meta-regression analysis, no relationship was observed between benefits in mortality, new MI, RI, and ST with new ADP antagonists and patients' risk profile [beta (95% CI) = -0.01 [-0.30 to 0.27], P = 0.94; beta (95% CI) = -0.05 [-1.49 to 1.43], P = 0.96); beta (95% CI) = 0.19 (-0.18 to 0.57), P = 0.31, and beta (95% CI) = -0.08 (-0.86 to 0.70), P = 0.84, respectively].ConclusionsPresent meta-analysis shows that the new ADP antagonists prasugrel, ticagrelor, and cangrelor are associated to significant reduction of mortality, reinfarction, RI, and ST respect to clopidogrel alone, without significant increase in bleeding complications.

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