Comparing DOACs with warfarin in AF patients with chronic kidney disease or valvular disease: A systematic review and meta-analysis

ObjectiveTo analyze the safety and efficacy of different direct oral anticoagulant agents (DOACs) compared to warfarin in patients with concomitant atrial fibrillation (AF) and valvular disease or concomitant AF and chronic kidney disease (CKD). MethodsWe conducted literature searches in MEDLINE, Embase, and EBM Reviews to examine randomized-controlled trials (RCTs) and non-RCTs that included the aforementioned patient populations treated with warfarin or DOAC (rivaroxaban, dabigatran, apixaban, or edoxaban) and assessed outcomes of bleeding, stroke, or systemic/arterial thromboembolism. Meta-analysis was performed for eligible studies using the Mantel-Haenszel method random-effects model. Results3,172 studies were screened and 154 studies were selected after two levels of screening. Meta-analysis showed that, in patients with concomitant AF and CKD, DOAC was associated with reduced bleeding in non-RCTs (OR 0.65, 95% Cl [0.49, 0.86], p=0.003), particularly in more severe CKD (eGFR < 60mL/min/1.73m2). Apixaban in particular was associated with reduced bleeding (OR 0.52, 95% Cl [0.44, 0.63], p<0.00001) and stroke incidence (OR 0.60, 95% Cl [0.41, 0.87], p=0.007). In patients with concomitant AF and valvular disease, DOAC was 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) in non-RCTs. ConclusionOur study studied populations that are typically excluded from large-scale anticoagulation studies and our findings suggest that DOACs may be superior to warfarin both in the prevention of thromboembolic event and in the reduction of bleeding risks in patients with concomitant CKD or valvular disease.