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

Contribution To Literature:

The ENVISAGE-TAVI AF trial showed that edoxaban is noninferior to VKAs for efficacy but did not meet criteria for noninferiority for bleeding among patients undergoing TAVR with either incident or prevalent AF.


The goal of the trial was to assess the efficacy and safety of edoxaban compared with vitamin K antagonists (VKAs) among patients undergoing transcatheter aortic valve replacement (TAVR) with either incident or prevalent atrial fibrillation (AF).

Study Design

Eligible patients were randomized in an open-label 1:1 fashion to either edoxaban 60 mg daily (n = 713) or VKA with an international normalized ratio (INR) goal of 2-3 (n = 713). Specified antiplatelet therapy in either trial group was allowed at the treating physician’s discretion, including dual antiplatelet therapy for up to 3 months after TAVR or single antiplatelet therapy indefinitely.

  • Total screened: 1,451
  • Total number of enrollees: 1,426
  • Median duration of follow-up: 540 days
  • Mean patient age: 82.1 years
  • Percentage female: 47.5%

Inclusion criteria:

  • Age ≥18 years
  • Successful TAVR without unresolved periprocedural complications
  • Prevalent or incident AF

Exclusion criteria:

  • Coexisting conditions conferring high risk of bleeding

Other salient features/characteristics:

  • Mean Society of Thoracic Surgeons risk score (predicted 30-day mortality): 4.9%
  • Prior stroke: 17%
  • Mean CHA2DS2-VASc score: 4.5
  • Supra-annular self-expanding valve: 46%; balloon-expandable valve: 48%
  • Median time within the therapeutic range in VKA arm: 68.2%

Principal Findings:

The primary efficacy outcome, all-cause mortality, myocardial infarction, ischemic stroke, systemic thromboembolic event, valve thrombosis, or major bleeding, for edoxaban vs. VKA, was 17.3/100 person-years (PY) vs. 16.5/100 PY (hazard ratio [HR] 1.05, 95% confidence interval [CI] 0.85-1.31, p = 0.01 for noninferiority).

  • Primary safety endpoint, major bleeding: 9.7/100 PY vs. 7/100 PY (HR 1.40, 95% CI 1.03-1.91, p = 0.93 for noninferiority)

Secondary outcomes for edoxaban vs. VKA:

  • All-cause mortality: 7.8/100 PY vs. 9.1/100 PY
  • Ischemic stroke: 2.1/100 PY vs. 2.8/100 PY
  • Valve thrombosis: 0 vs. 0
  • Intracranial hemorrhage: 1.5/100 PY vs. 2.1/100 PY


The results of this trial indicate that edoxaban is noninferior to VKA for efficacy but did not meet criteria for noninferiority for bleeding among patients undergoing TAVR with AF (bleeding events, primarily gastrointestinal bleeding events, were higher). There were no clinical valve thrombosis events. These results are overall similar to data with edoxaban among patients with AF but not undergoing TAVR; the higher bleeding rates are likely a reflection of the population enrolled: elderly and frail with multiple comorbidities.

In the GALILEO trial, low-dose rivaroxaban had worse outcomes compared with antiplatelet therapy among patients undergoing TAVR and who did not have an indication for oral anticoagulation (OAC). In the ATLANTIS trial, apixaban was superior to VKA in reducing valve thrombosis on 4D computed tomography among TAVR patients who had an indication for OAC, but had similar clinical outcomes. Among patients who did not have an indication for OAC, noncardiovascular mortality was higher with apixaban compared with antiplatelet therapy use.


Van Mieghem NM, Unverdorben M, Hengstenberg C, et al., on behalf of the ENVISAGE-TAVI AF Investigators. Edoxaban Versus Vitamin K Antagonist for Atrial Fibrillation After TAVR. N Engl J Med 2021;Aug 28:[Epub ahead of print].

Presented by Dr. George Dangas at the European Society of Cardiology Virtual Congress, August 28, 2021.

Clinical Topics: Anticoagulation Management, Arrhythmias and Clinical EP, Cardiac Surgery, Geriatric Cardiology, Invasive Cardiovascular Angiography and Intervention, Valvular Heart Disease, Anticoagulation Management and Atrial Fibrillation, Atrial Fibrillation/Supraventricular Arrhythmias, Cardiac Surgery and Arrhythmias, Cardiac Surgery and VHD, Interventions and Structural Heart Disease

Keywords: ESC Congress, ESC21, Anticoagulants, Atrial Fibrillation, Brain Ischemia, Frail Elderly, Geriatrics, Heart Valve Diseases, Hemorrhage, Intracranial Hemorrhages, Myocardial Infarction, Myocardial Ischemia, Platelet Aggregation Inhibitors, Stroke, Thromboembolism, Thrombosis, Transcatheter Aortic Valve Replacement, Vascular Diseases, Vitamin K

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