Anticoagulation strategies for atrial fibrillation (AF) with either edoxaban or vitamin K antagonists (VKA) were evaluated in patients post transcatheter aortic valve implantation (TAVI) in the ENVISAGE-TAVI AF trial. Edoxaban demonstrated non-inferiority in Net Adverse Clinical Events (NACE); however, due to a higher rate of major bleeding, there was no non-inferiority in the safety outcome1.
ENVISAGE-TAVI AF (NCT02943785) is a prospective randomised, open-label, blinded trial comparing edoxaban to VKA in AF patients with indication for chronic anticoagulation therapy after TAVI. The primary efficacy outcome was defined as NACE, comprising components such as all-cause death, myocardial infarction, or ischaemic stroke. An additional primary safety outcome was major bleeding as defined by the International Society on Thrombosis and Haemostasis (ISTH).
The study was designed as a non-inferiority trial with a positive result when the upper boundary of the 95% CI for the hazard ratio was below 1.38. At a mean of 67–70 hours after TAVI, the 1,426 participants were randomised to receive either 60 mg edoxaban daily or VKA as indicated to achieve an INR of 2–3. The average follow-up time was 548 days. At baseline, the study cohort included a mean age of 82 years with about equal rates for men and women, and an average creatinine clearance around 58 mL/min. Comorbidities were common with, for example, 83–87% congestive heart failure and about 41% coronary artery disease.
The primary efficacy outcome met the criteria of non-inferiority with a hazard ratio (HR) of 1.05 (95% CI 0.85–1.31; P=0.014). However, in the primary safety outcome, edoxaban did not reach significance due to a higher bleeding rate compared with VKA with an HR of 1.40 (95% CI 1.03–1.91; P=0.927). The analyses of stroke and all-cause death resulted in overall non-significant differences between the study arms.
In terms of safety, Prof. George Dangas (Mount Sinai Hospital, NY, USA) stated that higher rates of major bleeding with edoxaban were evident and driven by major gastro-intestinal bleedings. Of note, patients in the edoxaban group who required a dose reduction to 30 mg without receiving oral antiplatelet therapy had a similar rate of major bleeding compared with the VKA group, while in those taking antiplatelet treatment, the risk for major bleeding was in favour of the VKA regimen.
“Overall, this trial showed the non-inferiority of edoxaban compared with warfarin (or similar analogues) with respect to the composite efficacy endpoint of adverse clinical events. On the other hand, we need to be attentive to the higher bleeding risks with edoxaban. Based on secondary analyses, it seems that lowering the edoxaban dosage when indicated and avoiding patients on mandatory antiplatelet therapy is reasonable safety advice from a clinical point of view,” appraised Prof. Dangas.
1. Dangas GD. ENVISAGE-TAVI AF: edoxaban vs. vitamin K antagonists after TAVI in patients with atrial fibrillation. Hot Line Session, ESC Congress 2021, 27–30 August.