Reviwer: Dr. Alper Karakuş

Trial: Edoxaban vs. Standard of Care and Their Effects on Clinical Outcomes in Patients Having Undergone Transcatheter Aortic Valve Implantation–Atrial Fibrillation - ENVISAGE-TAVI AF

Presented Congress: ESC 2021

Full Text Link: https://www.nejm.org/doi/full/10.1056/NEJMoa2111016

Background:

The GALILEO trial demonstrated more harm than benefit with low-dose rivaroxaban compared to antiplatelet therapy in patients who underwent transcatheter aortic valve replacement (TAVR) and did not have atrial fibrillation (AF). In the ATLANTIS study, leaflet thrombosis was found to be lower with apixaban compared to antiplatelet therapy, but this did not show an improvement in clinical results.

Objective:

ENVISAGE-TAVI AF aimed to evaluate the efficacy and safety of edoxaban compared with vitamin K antagonists (VKA) in patients with TAVR and AF.

Method:

1426 patients were randomized (open-label and 1:1) to edoxaban 60 mg daily or VKA groups with an  international normalized ratio (INR) target of 2-3. The primary efficacy outcome was considered a composite of adverse events consisting of death from any cause, myocardial infarction, ischemic stroke, systemic thromboembolism, valve thrombosis, or major bleeding. The primary safety outcome was major bleeding. Primary efficacy and safety outcomes were tested for non-inferiority, with edoxaban compared to VKA at 95% confidence interval (CI) and the upper limit of 1.38 for Hazard ratio (HR).

Results:

Considering the demographic characteristics of the study population, the mean patient age was 82.1 years, the mean 30-day mortality predictive STS score was 4.9%, the mean CHA2DS2-VASc score was 4.5, and the mean TTR rate in the VKA arm was 68.2%. Almost all of the patients had AF before TAVR. The composite primary efficacy outcome ratio was 17.3 per 100 subjects per 1 year in the edoxaban arm and 16.5 per 100 subjects per 1 year in the VKA arm (HR:1.05; 95% CI, 0.85 to 1.31) and non-inferiority criteria were met (P=0.01). The major bleeding rate was 9.7 per 100 subjects per 1 year in the edoxaban arm and 7.0 per 100 subjects per 1 year in the VKA arm (HR:1.40; 95% CI, 1.03 to 1.91) and non-inferiority criteria were not met (P=0.93). When Edoxaban and VKA were compared in terms of secondary outcomes; all-cause mortality was 7.8 per 1 year in the edoxaban arm and 9.1 per 100 per 1 year in the VKA arm; 2.1 per 1 year in the ischemic stroke edoxaban arm and 2.8 per 100 per 1 year in the VKA arm; intracranial haemorrhage was 1.5 per 1 year in the edoxaban arm and 2.1 per 100 per 1 year in the VKA arm. No valve thrombosis was observed in either arm.

Conclusion:

nalysis showed that in patients with AF who underwent successful TAVR, edoxaban was non-inferior in efficacy to VKA (38% HR margin was established for the combined primary outcome of adverse clinical events). However, non-inferiority criteria was not meet for bleeding. Bleeding events, primarily gastrointestinal, were higher with edoxaban.

Interpretation:

The results of the study were similar to the data on edoxaban in patients with AF who did not receive TAVR, thus suggesting that edoxaban therapy may be valuable in the co-management of AF and TAVR. However, caution should be exercised against the higher risk of bleeding with edoxaban.