Safety and Efficacy of Selective, Clopidogrel-Based Strategies in Patients With Acute Coronary Syndrome: A Systematic Review and Meta-Analysis

Background: Selective, clopidogrel-based therapies after percutaneous coronary intervention (PCI) have been investigated to reduce the bleeding risk while maintaining an adequate anti-ischemic protection. However, single studies may be underpowered for events at low incidence, mainly major bleeding or ischemic complications. Methods: We performed an updated meta-analysis and meta-regression of randomized trials comparing outcome with unguided de-escalation to clopidogrel or guided clopidogrel therapy vs conventional treatment with potent oral P2Y12 inhibitors in patients undergoing PCI, especially for acute coronary syndrome (ACS). The primary safety endpoint was major bleeding. The primary efficacy endpoint was the incidence of major adverse cardiovascular events (MACE, cardiovascular death, myocardial infarction, stroke). Stent thrombosis was also an outcome measure. Findings: We considered six randomized trials, three on unguided de-escalation (N=3473) and three on guided clopidogrel therapy (N=7533). Control groups received conventional treatment with ticagrelor/prasugrel in all studies. The incidence of major bleeding was significantly lower with unguided de-escalation (1·0% vs 2·0% with conventional treatment; OR 0·53, 95% CI 0·30-0·95, p=0·03) and non-significantly reduced with guided de-scalation clopidogrel therapy (2·2% vs 3·6%; OR 0·79, 95% CI 0·49-1·27, p=0·33). Both unguided (3·3% vs 4·4%; OR 0·74, 95% CI 0·52-1·05, p=0·09) and guided clopidogrel therapy (2·8% vs 2·7%; OR 1·09, 95% CI 0·79-1·51, p=0·61) were associated with similar incidence of MACE vs conventional treatment. A trend towards an increased risk of stent thrombosis was observed in studies on guided clopidogrel therapy (OR 2·27, 95% CI 0·72-7·16, p=0·16). Meta-regression indicated greater safety and similar ischemic protection of the two alternatives clopidogrel-based therapies, regardless of baseline bleeding and ischemic risk. Interpretation: As compared with prasugrel/ticagrelor treatment, unguided de-escalation to clopidogrel, but no a guided clopidogrel therapy, decreases bleeding complications among patients with ACS undergoing PCI. Both unguided de-escalation and guided clopidogrel therapy appear as effective as in preventing MACE. Funding Information: None. Declaration of Interests: G.P.: speaker/consultant fee from Abbott, Astra Zeneca, Sanofi, Amgen, Menarini, Bayer, Pfizer, BMS, Daiichi Sankyo, PIAM, Malesci, Sigma Tau, Chiesi, Medtronic, MSD, Boehringer Ingelheim, Servier. L.G., E.G.S., A.R., M.M.: none.