Safety and Efficacy of Selective, Clopidogrel-Based Strategies in Acute Coronary Syndrome: A Study-Level Meta-analysis.

Objectives:  To investigate outcomes with selective, clopidogrel-based therapies versus conventional treatment in patients undergoing percutaneous coronary intervention (PCI), especially for acute coronary syndrome.

Background:  Safety and efficacy of alternative, selective, clopidogrel-based therapies after PCI are not robustly established.

Methods:  We performed a study-level meta-analysis on six randomized trials investigating selective clopidogrel-based therapies (three on unguided de-escalation,  = 3,473; three on guided clopidogrel therapy,  = 7,533). Control groups received ticagrelor or prasugrel treatment. Main endpoints were major bleeding, any bleeding, major adverse cardiovascular events (MACE), and net clinical endpoint.

Results:  The incidence of major bleeding and MACE was similar in the selective, clopidogrel-based therapy versus the conventional treatment arm (odds ratio [OR]: 0.72, 95% confidence interval [CI]: 0.51-1.01,  = 0.06; OR: 0.93, 0.72-1.20,  = 0.58; respectively). The rates of any bleeding were lower in the selective, clopidogrel-based therapy versus conventional treatment group (OR: 0.57, 95% CI: 0.40-0.80,  = 0.001); this greater safety was significant for unguided de-escalation (OR: 0.43, 95% CI: 0.32-0.58,  = 0.00001) and nonsignificant for guided clopidogrel therapy (OR: 0.72, 95% CI: 0.51-1.02,  = 0.07; for interaction: 0.03). The incidence of the net clinical endpoint was fewer in the selective, clopidogrel-based therapy versus the conventional treatment arm (OR: 0.59, 95% CI: 0.41-0.85,  = 0.004); this benefit was significant for unguided de-escalation (OR: 0.50, 95% CI: 0.39-0.64,  < 0.00001) and nonsignificant for guided clopidogrel therapy (OR 0.85, 95% CI: 0.62-1.16,  = 0.30; for interaction: 0.01).

Conclusion:  As compared with prasugrel/ticagrelor treatment, alternative, selective, clopidogrel-based approaches provide a similar protection from cardiovascular events, reduce the risk of any bleeding, and are associated with a greater net benefit. These beneficial effects were prevalent with unguided de-escalation to clopidogrel.