Meta-analysis of randomized controlled trials and adjusted observational results of use of clopidogrel, aspirin, and oral anticoagulants in patients undergoing percutaneous coronary intervention

The optimal antiaggregant therapy after coronary stenting in patients receiving oral anticoagulants (OACs) is currently debated. MEDLINE and Cochrane Library were searched for studies reporting outcomes of patients who underwent PCI and who were on triple therapy (TT) or dual-antiplatelet therapy (DAPT) with aspirin and clopidogrel or dual therapy (DT) with OAC and clopidogrel. Major bleeding was the primary end point, whereas 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. In 9 studies, 1,317 patients were treated with DAPT and 1,547 with TT. DAPT offered a significant reduction of major bleeding at 1 year for overall studies and for the subset of observational works providing adjusted data (odds ratio [OR] 0.51, 95% confidence interval [CI] 0.39 to 0.68, I2 60% and OR 0.36, 95% CI 0.28 to 0.46) compared to TT. No increased risk of major adverse cardiac events (MACE: death, MI, stroke, and stent thrombosis) was reported (OR 0.71, 95% CI 0.46 to 1.08), although not deriving from randomized controlled trials or multivariate analysis. Six studies tested OAC and clopidogrel (1,263 patients) versus OAC, aspirin, and clopidogrel (3,055 patients) with a significant reduction of bleeding (OR 0.79, 95% CI 0.64 to 0.98), without affecting rates of death, MI, stroke, and stent thrombosis (OR 0.90, 95% CI 0.69 to 1.23) also when including clinical data from randomized controlled trials or multivariate analysis. In conclusion, compared to TT, both aspirin and clopidogrel and clopidogrel and OAC reduce bleeding. No difference in major adverse cardiac events is present for clopidogrel and OAC, whereas only low-grade evidence is present for aspirin and clopidogrel.