Risk of Bleeding on Triple Antithrombotic Therapy After Percutaneous Coronary Intervention/Stenting: A Systematic Review and Meta-analysis

Abstract Background There are no reported randomized controlled trials of triple antithrombotic therapy (TT; aspirin plus a thienopyridine plus vitamin K antagonist) vs dual antiplatelet therapy (DAPT; aspirin plus a thienopyridine) among patients undergoing percutaneous coronary intervention with stenting (PCI-S). A systematic review and meta-analysis was undertaken to assess the risk of bleeding among patients receiving TT after PCI-S. Methods Electronic databases were searched for studies reporting bleeding among patients receiving TT after PCI-S. Of the 4108 articles screened, 18 met study inclusion criteria and underwent detailed data extraction: of these, 6 reported in-hospital outcomes, 14 reported 30-day outcomes, and 9 reported 6-month outcomes. At each time point, pooled estimates of bleeding with TT were ascertained and where possible summary odds ratios (ORs) for comparative risks vs DAPT were calculated. Results The pooled estimate of major bleeding rate with TT post PCI-S was 2.38% by 30 days postprocedure (95% confidence interval [CI], 0.98-3.77%) and 4.55% by 6 months postdischarge (95% CI, 0.56-8.53%). At 30 days and 6 months the rates of major bleeding with TT were significantly higher than those observed with DAPT: OR, 2.38 at 30 days (95% CI, 1.05-5.38) and OR, 2.87 at 6 months (95% CI, 1.47-5.62). Conclusions This systematic review and meta-analysis of reports of triple therapy with a vitamin K antagonist, aspirin, and clopidogrel after PCI-S provides precise and valid bleeding risk data. Based on existing observational studies the rates of major and any bleeding associated with TT are clinically important and significantly greater than those reported with DAPT.