Direct oral anti-coagulants in patients with atrial fibrillation and bioprosthetic valve: a meta-analysis of randomized controlled trials

Abstract

Background: Patients with atrial fibrillation (AF) and bioprosthetic valve (BPV) are at increased risk for thromboembolic events and require anticoagulation. However, management strategies for these patients have not yet been well addressed by randomized controlled trials (RCTs). For years, warfarin was the only available oral anticoagulant, but this changed with the introduction of the direct oral anticoagulants (DOACs). However, there is no clear consensus about indications for DOACs in these patients due to the lack of prospective trials. Purpose(s): The objective of this meta-analysis is to show the efficacy of DOACs in AF patients with BPV in terms of composite cardiovascular outcomes. In addition, the study aims to show the safety of DOACs in terms of major bleeding. Method(s): A comprehensive literature search for randomized controlled trials (RCTs) was performed in MEDLINE, PubMed and Clinicaltrials.gov in human subjects done within 2010 to 2020. Results were pooled using fixed effects. The primary outcome was a composite cardiovascular outcome from all included studies, which include death, major bleeding and major adverse cardiac events (stroke, transient ischemic attack, valve thrombosis, myocardial infarction, systemic embolism, and hospitalization for heart failure). Secondary outcomes include all-cause stroke or systemic embolism, major bleeding, death from cardiovascular cause and all-cause death. Result(s): Four RCTs were included in the meta-analysis. DOACs used were Apixaban, Dabigatran, Edoxaban and Rivaroxaban. In patients with AF and BPV, DOACs performed similarly with warfarin in terms of composite cardiovascular outcome (RR 1.01, 95% CI 0.86-1.19, P=0.88, I2=0%). On the other hand, DOACs performed better than warfarin in reduction of all cause stroke and systemic embolism (RR 0.48, 95% CI 0.27-0.87, P=0.01). There is non-statistically significant risk reduction for major bleeding (RR 0.81, 95% CI 0.56-1.17, P=0.26, I2=0%) and other secondary outcomes such as death from cardiovascular causes (RR 0.79, 95% CI 0.39- 1.60, P=0.51, I2=0%) and all cause death (RR 0.94, 95% CI 0.55-1.62, P=0.71, I2=0%) showing similar outcomes with NOACs and warfarin. Conclusion(s): DOACs compared with warfarin are similar in terms of composite cardiovascular outcome, major bleeding and death. However, DOACs performed better than warfarin in reducing all-cause stroke/systemic embolism and can be an alternative for oral anticoagulation in patients with AF and BPV.