Trial Sequential Analysis Comparing Bleeding and Major Adverse Cardiovascular Events in Patients with Atrial Fibrillation and Acute Coronary Syndrome on Dual versus Triple Therapy

Abstract

Objective To assess efficacy and safety of dual therapy (DT) and triple therapy (TT) in patients with atrial fibrillation (AF) and acute coronary syndrome (ACS) with or without percutaneous coronary intervention (PCI) and evaluate the quality of evidence with respect to said outcomes based on contemporary randomized trials (RCTs). The efficacy outcome taken was major adverse cardiovascular events (MACE) while safety outcome was major bleeding events. Introduction Appropriate anti-thrombotic therapy is still controversial in patients with AF and concomitant ACS or PCI. We conducted a conventional meta-analysis pooling data from major RCTs to assess the efficacy and safety of DT and TT. Additionally, we utilized advanced analytic properties of trial sequential analysis (TSA) to assess for quality of evidence in this realm. Methods and results A total of 8,732 patients from five major RCTs were enrolled in this study. There was a statistically significant reduction in major bleeding on the DT group compared to the TT group (RR 0.65, 95% CI 0.48, 0.86). The incidence of major adverse cardiovascular events (MACE) was similar in both groups (RR 0.97, 95% CI 0.8,1.17). The trial sequential analysis showed strong evidence supporting reduction in bleeding from current major RCTs while being inconclusive based on MACE outcome. Conclusion Sufficient quality evidence could be ascertained from contemporary RCTs on reduced incidence of bleeding in DT patients compared to TT patients. Further adequately powered RCTs are needed to ensure non-inferiority of DT over TT with respect to MACE outcome.