Study Shows New P2Y₁₂ Inhibitors Decrease Mortality in PCI Compared to Clopidogrel

November 2, 2010—In the Journal of the American College of Cardiology, Anne Bellemain-Appaix, MD, et al have published findings from a meta-analysis of randomized trials that compare new P2Y₁₂ inhibitors with clopidogrel to determine whether the they improve clinical outcomes after percutaneous coronary intervention (PCI) (2010;56:1542–1551).

The investigators concluded that new P2Y₁₂ inhibitors decrease mortality after PCI compared with clopidogrel, and that the risk/benefit ratio is particularly favorable in PCI for STEMI patients.

According to the investigators, the background of the study is that 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, but it is unknown if they decrease mortality after PCI compared with clopidogrel.

As detailed in the study, the investigators searched MEDLINE and Cochrane Controlled Trials Register databases from January 1980 through January 2010. They selected randomized, placebo-controlled trials that compared new P2Y₁₂ antagonists with clopidogrel in PCI. Data from eight studies were evaluated and analyses performed for all randomized patients, PCI patients (any PCI), and PCI for ST-segment elevation myocardial infarction (STEMI) patients. The primary efficacy endpoint was all-cause mortality. Thrombolysis in myocardial infarction (TIMI) major bleeding was the primary safety endpoint.

A total of 48,599 patients were included, with 94% of patients with acute coronary syndrome and 84% of patients undergoing PCI.

The investigators reported that new P2Y₁₂ inhibitors significantly decreased death (odds ratio [OR], 0.83; 95% confidence interval [CI], 0.75–0.92; P < .001 for the whole cohort; OR, 0.85; 95% CI, 0.75–0.96; P = .008 for any PCI; and OR, 0.78; 95% CI, 0.66–0.92; P = .003 for PCI for STEMI). In PCI patients, new P2Y₁₂ inhibitors also significantly decreased major adverse cardiac events by 18% (P < .001) and stent thrombosis by 40% (P < .001). Although there was an increase in TIMI major bleeding for any PCI (OR, 1.23; 95% CI, 1.04–1.46; P = .01), no difference was observed in PCI for STEMI (OR, 0.98; 95% CI, 0.85–1.13; P = .76), with similar outcomes in primary PCI for STEMI. Results were confirmed in sensitivity analyses that removed the largest study, the investigators advised.