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New P2Y12 Inhibitors Versus Clopidogrel in Percutaneous Coronary Intervention

A Meta-Analysis

Institut de Cardiologie, Pitié-Salpêtrière University Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France

Manuscript received June 3, 2010; revised manuscript received July 20, 2010, accepted July 26, 2010.

^_* Reprint requests and correspondence: Dr. Gilles Montalescot, Institut de Cardiologie, Bureau 2-236, Pitié-Salpêtrière Hospital, 47 Boulevard de l'Hôpital, 75013 Paris, France. (Email: gilles.montalescot{at}psl.aphp.fr).

Objectives: The purpose of this study was to perform a meta-analysis of randomized trials that compare new P2Y12 inhibitors with clopidogrel to determine whether they improve clinical outcomes after percutaneous intervention (PCI).

Background: Ticlopidine/clopidogrel prevents major adverse cardiac events after PCI, but no trials have shown an effect on mortality. New P2Y12 inhibitors are more potent and evaluated in PCI. Whether they decrease mortality after PCI compared with clopidogrel is unknown.

Methods: MEDLINE and Cochrane Controlled Trials Register databases were searched from January 1980 through January 2010. Randomized, placebo-controlled trials that compared new P2Y12 antagonists with clopidogrel in PCI were selected. Data from 8 studies were evaluated and analyses performed for all randomized patients, PCI patients (any PCI), and PCI for ST-segment elevation myocardial infarction (STEMI) patients. All-cause mortality was the primary efficacy end point. Thrombolysis In Myocardial Infarction major bleeding was the primary safety end point.

Results: A total of 48,599 patients were included with 94% of patients with acute coronary syndrome and 84% of patients undergoing PCI. New P2Y12 inhibitors significantly decreased death (odds ratio [OR]: 0.83, 95% confidence interval [CI]: 0.75 to 0.92, p < 0.001 for the whole cohort; OR: 0.85, 95% CI: 0.75 to 0.96, p = 0.008 for any PCI; and OR: 0.78, 95% CI: 0.66 to 0.92, p = 0.003 for PCI for STEMI). In PCI patients, new P2Y12 inhibitors also significantly decreased major adverse cardiac events by 18% (p < 0.001) and stent thrombosis by 40% (p < 0.001). Although there was an increase in Thrombolysis In Myocardial Infarction major bleeding for any PCI (OR: 1.23, 95% CI: 1.04 to 1.46, p = 0.01), no difference was observed in PCI for STEMI (OR: 0.98, 95% CI: 0.85 to 1.13, p = 0.76), with similar outcomes in primary PCI for STEMI. Results were confirmed in sensitivity analyses that removed the largest study.

Conclusions: New P2Y12 inhibitors decrease mortality after PCI compared with clopidogrel. The risk/benefit ratio is particularly favorable in PCI for STEMI patients.

Key Words: acute coronary syndrome • cangrelor • clopidogrel • elinogrel • P2Y12 antagonists • percutaneous coronary intervention • prasugrel

Abbreviations and Acronyms   ACS = acute coronary syndromes   CI = confidence interval   CV = cardiovascular   MACE = major adverse cardiac event   MI = myocardial infarction   OR = odds ratio   PCI = percutaneous coronary intervention   ST = stent thrombosis   STEMI = ST-segment elevation myocardial infarction   TIMI = Thrombolysis In Myocardial Infarction

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