In atrial fibrillation patients with valvular heart disease, higher-dose edoxaban showed similar efficacy to warfarin for preventing stroke or systemic embolic events (HR 0.69; 95% CI 0.44-1.07).
RCT (n=21,046)
Yes
Does edoxaban improve efficacy and safety compared to warfarin in patients with atrial fibrillation and coexisting valvular heart disease?
Edoxaban maintains its relative efficacy and safety compared to warfarin in patients with atrial fibrillation regardless of the presence of coexisting valvular heart disease.
Hazard Ratio: 0.69 (95% CI 0.44–1.07)
The use of non-vitamin K antagonist oral anticoagulants (NOACs) instead of vitamin K antagonists (VKAs) in patients with atrial fibrillation (AF) and coexisting valvular heart disease (VHD) is of substantial interest. This study explored outcomes in patients with AF with and without VHD in the ENGAGE AF–TIMI 48 (Effective Anticoagulation with factor Xa Next Generation in Atrial Fibrillation-Thrombolysis In Myocardial Infarction 48) trial, comparing edoxaban with warfarin. Valvular heart disease was defined as history or baseline echocardiography evidence of at least moderate aortic/mitral regurgitation, aortic stenosis, or prior valve surgery (bioprosthesis replacement, valve repair, valvuloplasty). Patients with moderate to severe mitral stenosis or mechanical heart valves were excluded from the trial. Comparisons were made of rates of stroke/systemic embolic event (SSEE), major bleeding, additional efficacy and safety outcomes, as well as net clinical outcomes, in patients with or without VHD treated with edoxaban or warfarin, using adjusted Cox proportional hazards. After adjustment for multiple baseline characteristics, compared with no-VHD patients (n = 18,222), VHD patients (n = 2,824) had a similar rate of SSEE but higher rates of death (hazard ratio HR: 1.40; 95% confidence interval CI:1.26 to 1.56; p <0.001), major adverse cardiovascular events (HR: 1.29; 95% CI: 1.16 to 1.43; p <0.001), and major bleeding (HR: 1.21; 95% CI: 1.03 to 1.42; p = 0.02). Higher-dose edoxaban regimen had efficacy similar to warfarin in the presence of VHD (for SSEE, HR: 0.69; 95% CI: 0.44 to 1.07, in patients with VHD, and HR: 0.91; 95% CI: 0.77 to 1.07, in patients without VHD; p interaction pint = 0.26; and for less major bleeding, HR: 0.74; 95% CI: 0.53 to 1.02 in patients with VHD, and HR: 0.82; 95% CI: 0.71 to 0.94, in patients with no VHD; pint = 0.57). The presence of VHD increased the risk of death, major adverse cardiovascular events, and major bleeding but did not affect the relative efficacy or safety of higher-dose edoxaban versus warfarin in AF. (Global Study to Assess the Safety and Effectiveness of Edoxaban (DU-176b) vs. Standard Practice of Dosing With Warfarin in Patients With Atrial Fibrillation ENGAGE AF-TIMI 48; NCT00781391)
Caterina et al. (Wed,) conducted a rct in Atrial fibrillation with and without valvular heart disease (n=21,046). Edoxaban vs. Warfarin was evaluated on Stroke/systemic embolic event (SSEE) in patients with valvular heart disease (HR 0.69, 95% CI 0.44-1.07). In atrial fibrillation patients with valvular heart disease, higher-dose edoxaban showed similar efficacy to warfarin for preventing stroke or systemic embolic events (HR 0.69; 95% CI 0.44-1.07).