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Published on: February 28, 2012
Valvular Heart Disease Patients on Edoxaban or Warfarin in the ENGAGE AF-TIMI 48 Trial
Raffaele De Caterina1, Giulia Renda1, Anthony P Carnicelli2
1Institute of Cardiology and Center of Excellence on Aging, G. d'Annunzio University, Chieti, Italy.
Insights
Patients with valvular heart disease (VHD) and atrial fibrillation (AF) face higher risks of death, cardiovascular events, and bleeding. However, edoxaban and warfarin showed similar efficacy and safety in this population.
Area of Science:
- Cardiology
- Pharmacology
- Clinical Trials
Background:
- Non-vitamin K antagonist oral anticoagulants (NOACs) are increasingly used for atrial fibrillation (AF).
- The safety and efficacy of NOACs versus vitamin K antagonists (VKAs) in AF patients with coexisting valvular heart disease (VHD) require investigation.
Purpose of the Study:
- To compare outcomes in AF patients with and without VHD treated with edoxaban or warfarin.
- To assess the relative efficacy and safety of edoxaban versus warfarin in patients with VHD.
Main Methods:
- Analysis of data from the ENGAGE AF-TIMI 48 trial, comparing edoxaban and warfarin.
- VHD defined by moderate/severe regurgitation, stenosis, or prior valve surgery.
- Outcomes included stroke/systemic embolic events (SSEE), major bleeding, and net clinical outcomes using adjusted Cox proportional hazards.
Main Results:
- VHD patients (n=2,824) had similar SSEE rates but higher rates of death (HR 1.40), major adverse cardiovascular events (HR 1.29), and major bleeding (HR 1.21) compared to no-VHD patients (n=18,222).
- Higher-dose edoxaban demonstrated efficacy similar to warfarin for SSEE (pint=0.26) and less major bleeding (pint=0.57) in VHD patients.
- No significant interaction was observed for efficacy or safety outcomes between edoxaban and warfarin based on VHD status.
Conclusions:
- Valvular heart disease increases risks of death, MACE, and major bleeding in AF patients.
- Higher-dose edoxaban and warfarin show comparable efficacy and safety profiles in AF patients with VHD.
- VHD presence does not alter the relative effectiveness or safety of edoxaban compared to warfarin.
Background:
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.
Objectives:
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.
Methods:
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.
Results:
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).
Conclusions:
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).
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