Anti-Thrombotic Strategy to Lower All cardiovascular and Neurologic Ischemic and Hemorrhagic Events after Trans-Aortic Valve Implantation for Aortic Stenosis - ATLANTIS

Contribution To Literature:

The ATLANTIS trial showed that full-dose apixaban is not superior to standard of care (VKA if indication for OAC; APT if no indication) among patients undergoing TAVR despite a reduction in valve leaflet thrombosis (compared with APT).

Description:

The goal of the trial was to assess the efficacy and safety of apixaban 5 mg BID compared with standard of care (antiplatelet therapy [APT] or oral anticoagulant [OAC]) among patients undergoing transcatheter aortic valve replacement (TAVR).

Study Design

Eligible patients were stratified based on indication of OAC, and randomized in a 1:1 fashion to either apixaban 5 mg BID vs. vitamin K antagonist (VKA) (21%) [stratum 1 = among patients with an indication for OAC, n = 451], or apixaban 5 mg BID vs. single APT (15%)/dual APT (57%) [stratum 2 = among patients without an indication for OAC, n = 1,049].

  • Total number of patients: 1,500
  • Duration of follow-up: 1 year
  • Mean patient age: 82 years
  • Percentage female: 53%

Inclusion criteria:

  • Age ≥18 years
  • Successful native or valve-in-valve TAVR
  • Approved/marketed TAVR device

Exclusion criteria:

  • Creatinine clearance <15 ml/min or dialysis
  • Mechanical valves
  • Severe mitral valve stenosis requiring an intervention
  • Unsuccessful TAVR requiring re-intervention
  • Ongoing major bleeding or vascular complication
  • Prior history of intracranial hemorrhage
  • Recent stroke/transient ischemic attack (TIA) on anticoagulant therapy (<6 weeks)
  • Planned major surgery during follow-up
  • Expected survival <1 year
  • Concomitant use of prasugrel or ticagrelor
  • Coronary stent implantation <2 weeks prior to randomization
  • Concomitant treatments that are potent inhibitors of CYP3A4
  • Any coagulopathy and significant risk of bleeding

Other salient features/characteristics:

  • Society of Thoracic Surgeons Predicted Risk of Mortality (STS-PROM) score: 5.1%
  • Prior stroke: 11%
  • CHA2DS2-VASc score: 4.3
  • Self-expanding valve: 53%; balloon-expandable valve: 47%; valve-in-valve: 5%

Principal Findings:

The primary outcome, time to death, stroke, myocardial infarction (MI), systemic emboli, intracardiac or valve thrombosis, deep vein thrombosis/pulmonary embolism, or major bleeding, for apixaban vs. standard of care: 18.4 vs. 20.1% (hazard ratio [HR] 0.92, 95% confidence interval CI 0.73-1.16).

  • Stratum 1: apixaban vs. VKA: 21.9% vs. 21.9%
  • Stratum 2: 16.9% vs. 19.3%
  • p for interaction = 0.57
  • Without including valve thrombosis in composite endpoint: 17.8% vs. 16.1% (HR 1.12, 95% CI 0.88-1.44)

Primary safety endpoint: 8.5% vs. 8.5%

  • Bioprosthetic thrombosis: 1.1% vs. 4.7% (p < 0.05)
  • Stratum 1: apixaban vs. VKA: 0.9% vs. 1.3% (p > 0.05)
  • Stratum 2: Apixaban vs. APT: 1.1% vs. 6.1% (p < 0.05)

4D-CT subset (n = 762):

The primary outcome, ≥1 prosthetic leaflet with reduced leaflet motion (RLM) grade 3/4 or hypoattenuated leaflet thrombosis (HALT) grade 3/4 at 90 days, for apixaban vs. standard of care, was 8.9% vs. 13.0% (p = 0.038).

  • Stratum 1: 9.5% vs. 5.5% (p = 0.28)
  • Stratum 2: 8.7% vs. 15.9% (p = 0.011)

Secondary outcomes for apixaban vs. standard of care:

  • Death/MI/stroke: 10.5% vs. 8.3% (HR 1.32, 95% CI 0.95-1.85)
  • All-cause mortality: 7.2% vs. 5.5%
  • Venous thromboembolism event: 0.1% vs. 1.5% (p < 0.05)
  • Major bleeding: 6.7% vs. 6.4%
  • Noncardiovascular mortality for apixaban vs. APT (stratum 2): 2.7% vs. 1.0% (p < 0.05)

4D-CT subset:

  • Patients without presence of thrombus at 90 days: 19.2% vs. 25% (p = 0.011)

Interpretation:

The results of this trial indicate that apixaban is not superior to standard of care (VKA if indication for OAC; APT if no indication) among patients undergoing TAVR. Valve leaflet thrombosis was lower with apixaban compared with APT, but this did not translate into an improvement in clinical outcomes. In fact, among patients without an indication for OAC, apixaban use resulted in higher noncardiovascular mortality compared with APT use. Results are similar to the GALILEO trial with low-dose rivaroxaban. These data do, however, support the use of apixaban instead of VKA if needed among patients requiring long-term OAC.

References:

Presented by Dr. Jean-Philippe Collet at the American College of Cardiology Virtual Annual Scientific Session (ACC 2021), May 15, 2021.

Presented by Dr. Gilles Montalescot at the American College of Cardiology Virtual Annual Scientific Session (ACC 2021), May 15, 2021.

Clinical Topics: Anticoagulation Management, Cardiac Surgery, Cardiovascular Care Team, Geriatric Cardiology, Invasive Cardiovascular Angiography and Intervention, Valvular Heart Disease, Aortic Surgery, Cardiac Surgery and VHD, Interventions and Structural Heart Disease, Interventions and Vascular Medicine

Keywords: ACC21, ACC Annual Scientific Session, Anticoagulants, Aortic Valve Stenosis, Cardiac Surgical Procedures, Geriatrics, Heart Valve Diseases, Heart Valve Prosthesis, Hemorrhage, Myocardial Infarction, Platelet Aggregation Inhibitors, Pulmonary Embolism, Standard of Care, Stroke, Thrombosis, Transcatheter Aortic Valve Replacement, Venous Thrombosis, Vitamin K


< Back to Listings