https://orcid.org/0000-0002-0366-1547
Abstract
Direct oral anticoagulant agents (DOACs) are indicated to prevent vascular events in patients with atrial fibrillation (AF) without concomitant valvular disease or severe chronic kidney disease (CKD), groups in which warfarin is the preferred choice. We aimed to evaluate the safety of DOACs in the aforementioned populations compared to warfarin. We conducted a systematic review in MEDLINE, Embase, and EBM Reviews to identify randomized-controlled trials (RCTs) and non-RCTs assessing warfarin or DOAC (rivaroxaban, dabigatran, apixaban, or edoxaban) in patients with AF with concomitant valvular disease or CKD (according to KDOQI guidelines), and that assessed bleeding, stroke, or systemic/arterial thromboembolism. Meta-analysis was performed for eligible studies using the Mantel-Haenszel method random-effects model. Of 3,172 screened studies, we included 110 studies (310,478 patients with concomitant AF and CKD; 99,299 patients with concomitant AF and valve disease). Meta-analysis showed that compared to warfarin, in patients with concomitant AF and CKD, DOACs were associated with reduced bleeding (OR 0.66, 95% Cl [0.49, 0.88], p=0.005) and strokes (OR 0.60, 95% CI [0.43, 0.85]; p=0.004), particularly in stages 4 and 5 CKD and in dialysis patients. In patients with concomitant AF and valvular disease, DOACs were associated with reduced bleeding (OR 0.75, 95% CI [0.57, 0.97], p=0.03) and stroke incidence (OR 0.66, 95% CI [0.47, 0.93], p=0.02). Differences were noted for RCTs and non-RCTs. Our findings suggest that DOACs may be equivalent or superior to warfarin both in the prevention of thromboembolic event and reduction of bleeding in the aforementioned patients.
