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Benefits From New ADP Antagonists as Compared With Clopidogrel in Patients With Stable Angina or Acute Coronary Syndrome Undergoing Invasive Management: A Meta-analysis of Randomized Trials

Verdoia, Monica MD*; Schaffer, Alon MD*; Barbieri, Lucia MD*; Cassetti, Ettore MD*; Piccolo, Raffaele MD; Galasso, Gennaro MD; Marino, Paolo MD*; Sinigaglia, Fabiola MD, PhD; De Luca, Giuseppe MD, PhD*

Journal of Cardiovascular Pharmacology: April 2014 - Volume 63 - Issue 4 - p 339–350
doi: 10.1097/FJC.0000000000000052
Original Article

Aims: New 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 Results: Literature 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].

Conclusions: Present 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.

*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.

Reprints: Giuseppe De Luca, MD, PhD, Division of Cardiology, Azienda Ospedaliera-Universitaria “Maggiore della Carità,” Eastern Piedmont University, Mazzini, 18, Novara 28100, Italy (e-mail:

The authors report no conflicts of interest.

Received August 05, 2013

Accepted November 18, 2013

© 2014 by Lippincott Williams & Wilkins.