ANTITHROMBOTIC THERAPIES FOR PATIENTS WITH AN INDICATION FOR ANTICOAGULATION AND STABLE CORONARY ARTERY DISEASE: A NETWORK META-ANALYSIS

Abstract

The optimal antithrombotic strategy for patients with atrial fibrillation and stable coronary artery disease (CAD) remains unclear. Oral anticoagulation (OAC) is indicated for the prevention of AF-related stroke and systemic embolism, whereas single antiplatelet therapy (SAPT) is indicated for the primary and secondary prevention of coronary events. We sought to determine if OAC alone a reasonable alternative to SAPT for the management of ischemic coronary outcomes in the non-ACS population, and whether there was incremental benefit to the addition of antiplatelet therapy to OAC therapy (dual pathway therapy - DT). We conducted a systematic review of studies in patients with coronary artery disease that reported a comparison of ASA, OAC, or DT, and presented absolute rates for safety outcomes (major bleeding) and efficacy outcomes (ischemic stroke, myocardial infarction, and all-cause mortality). A network meta-analysis was conducted to directly and indirectly compare the efficacy and safety with a Bayesian random-effects model. Results were presented as relative risks (RRs) and 95% confidence intervals (CIs). Fourteen randomized and six observational studies with 128,908 patients were included. Compared to SAPT, OAC alone reduced the risk of stroke (RR 0.66; 95%CI 0.49-0.87), and recurrent MI (RR 0.77; 95%CI 0.60-0.98), with a trend to reduced all-cause mortality (RR 0.85, 95%CI 0.68-1.06). Conversely DT was only superior to SAPT for stroke reduction (RR 0.77; 95%CI 0.61-0.99), with negligible influence on all-cause mortality and only a trend to reduction in recurrent MI. Both OAC and DT significantly increased the risk of bleeding over SAPT alone (RR 1.47, 95%CI 1.21-1.78 for OAC alone, and RR 2.02, 95%CI 1.70-2.39 for DT), however OAC alone was associated with significantly less major bleeding compared to DT (RR 0.73; 95%CI 0.64-0.83). Restricting the analysis to the 14 randomised studies (52,095 patients) reduced the power without substantially changing the point estimates. In patients with stable CAD at risk of AF-associated stroke/systemic embolism, OAC alone provides optimal protection against both stroke and ischemic coronary events. The addition of antiplatelet therapy to OAC offers no additional beneficial effect on ischemic or thrombotic coronary outcomes, while conferring a significantly increased risk of bleeding.