Use of clopidogrel, aspirin and oral anti-coagulant therapy in patients undergoing percutaneous coronary intervention: a meta-analysis of randomized controlled trials and adjusted observational result

Introduction: The optimal antiaggregant therapy after coronary stenting in patients under oral anticoagulation (OAC) is currently debated. Methods: Medline and Cochrane Library were searched for studies reporting outcomes of patients undergoing PCI and who were on triple therapy (TT) or double therapy (DT either aspirin and clopidogrel or OAC and clopidogrel). Major bleeding was the primary end point, while all-cause death, myocardial infarction (MI), stent thrombosis and stroke were secondary ones. Results were reported for all studies, and separately for those deriving from randomized controlled trials or multivariate analysis. Results: In eight studies 1354 patients treated with double therapy (DT) were on aspirin and clopidogrel: a significant reduction of major bleeding for DT patients was demonstrated for overall studies and for the subset of RCT and observational studies providing adjusted data (odds ratio OR 0.46 [95% confidence interval 0.36-0.65] and OR 0.36 [0.28-0.46]). No increase risk of major adverse cardiac events (MACE: death, myocardial infarction, stroke and stent thrombosis) was reported (OR 0.85 [0.57-1.28]), although not deriving from randomized controlled trials or multivariate analysis. Six studies with 5758 patients tested OAC and clopidogrel as DT with a significant reduction of bleeding (0.79 [0.63, 0.98]), without affecting rates of death, myocardial infarction, stroke and stent thrombosis (0.90 [0.69, 1.17] I2) also when including clinical data from randomized controlled trials or multivariate analysis. Conclusions: When compared to TT, DT (clopidogrel and OAC or aspirin and clopidogrel) reduces bleeding. No difference in major adverse cardiac events is present for DT with OAC and clopidogrel, while only low grade evidence is present for aspirin and clopidogrel.