The efficacy and safety of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation and coronary artery disease: A meta-analysis of randomized trials

Abstract

Background: Patients with atrial fibrillation and concomitant coronary artery disease (CAD) are at higher risk for myocardial infarction or cardiovascular death, often require antiplatelet therapy and are therefore exposed to an increased risk of bleeding. This meta-analysis aimed to compare the efficacy and safety profile of non-vitamin K antagonist oral anticoagulants (NOACs) with warfarin in patients with atrial fibrillation and concomitant CAD. Materials and methods: We performed a trial-level meta-analysis of CAD subgroups from four trials of NOAC versus warfarin in patients with atrial fibrillation, comparing the primary trial endpoints (efficacy: stroke or systemic embolic event; safety: International Society on Thrombosis and Haemostasis major bleeding) in patients with versus those without CAD, and used interaction testing to assess for treatment effect modification. Results: In total, 58,606 patients with established CAD were included in this meta-analysis. NOACs reduced the risk of stroke/systemic embolic event irrespective of presence of CAD (CAD: 0.76 (0.56–1.04); no CAD: hazard ratio 0.77 (0.56–1.06); p-INT 0.93). Similarly, there was no effect modification by presence of CAD for major bleeding (CAD: hazard ratio 0.92 (0.65–1.32), no CAD: 0.83 (0.61–1.12); p-INT 0.46) or myocardial infarction (CAD: hazard ratio 0.95 (0.62–1.44); no CAD: hazard ratio 0.95 (0.60–1.50); p-INT = 0.98). While NOACs reduced all-cause mortality in patients without CAD compared with warfarin (hazard ratio 0.85 (0.71–1.02)), there was no difference in mortality between NOACs and warfarin in the CAD group (hazard ratio 0.99 (0.82–1.20); p-INT 0.01). Conclusion: The present meta-analysis of four trials supports that NOACs are safe and at least as effective as warfarin in patients with atrial fibrillation and established CAD.