Apixaban Use Post-TAVR is Not Superior to Standard of Care

Jean-Phillipe Collet, MD, PhD

New late-breaking data from the American College of Cardiology (ACC) Annual Scientific Session indicates that non-vitamin K antagonist blood thinner apixaban was not superior to standard of care following transcatheter aortic valve replacement (TAVR).

Currently, there is great uncertainty surrounding the best post-operative preventative strategies for reducing risk of bleeding and blood clots and related adverse events.

“The role of chronic anticoagulation therapy remains debated versus antiplatelet therapy and even more for Non-vitamin K Oral Anti-Coagulants (NOAC), which have shown unfavorable results in patients with prosthetic heart valves,” explained the study investigators, led by Jean-Phillipe Collet, MD, PhD, of Groupe Hospitalier Pitié-Salpêtrière in Paris.

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In this international randomized open-label ATLANTIS trial, the investigators evaluated a total of 1510 patients who successfully completed a TAVI procedure. Patients were then stratified according to whether or not they were indicated for anti-coagulation therapy.

Regardless of stratification, patients were then randomized 1:1 to apixaban 5 mg, 2.5 mg (alone or in combination with antiplatelet therapy) twice a day or standard of care.

For patients requiring anticoagulation, standard of care was vitamin K antagonist (VKA) warfarin. For those not indicated for anticoagulation, the standard of care was antiplatelet medication. 

As such, the primary endpoint was the composite of death, myocardial infarction (MI), stroke, systemic emboli, intracardiac or bioprosthesis thrombus, episodes of deep vein thrombosis or pulmonary embolism, and major bleedings over the course of 1 year.

Included patients were ≥18 years of age and a mixture of both antithrombotic therapy-naïve and experienced. Patients with creatine clearance <15 mL/min or dialysis, mechanical valves, or any coagulopathies and significant risk of bleeding, among sever other criteria, were excluded.

Overall, patients in the apixaban arm experienced a total of 138 (18.4%) primary endpoint events—compared with 151 (20.1%) events in the standard of care arm (hazard ratio [HR], 0.92; 95% CI, 0.73-1.16).

Among patients with no indication for anti-coagulation therapy, 89 (16.9%) events occurred in the apixaban arm and 101 (19.3%) events in the standard of care arm (HR, 0.88; 95%, 0.66-1.17). For patients with an indication, 49 (21.9%) and 50 (21.9%) events occurred in the apixaban and standard of care arms, respectively (HR, 1.02; 95% CI, 0.68-1.51).

However, patients who received apixaban demonstrated higher numbers of secondary endpoints, which included death, stroke, heart attack, or systemic embolism.

For example, 79 (10.5%) patients experienced death, MI, or any stroke—versus 62 (8.26%) of standard of care patients (HR, 1.32; 95% CI, 0.95-1.85). Overall death from cardiovascular and non-cardiovascular causes occurred in 54 (7.2%) apixaban and 41 (5.5%) standard of care patients.

“This difference, although not significant, was unexpected and driven only by the cohort of patients who did not have an indication for oral anticoagulation and only by the rate of non-cardiovascular death,” Collet said in a statement.

“Among the subset of patients who are in need of oral anticoagulation, the results suggest that apixaban may be the default treatment given its ease of use and track record in atrial fibrillation,” he continued.

And finally, according to 4D CT scans of the implanted valve, apixaban users had an 80% lower rate of clot formation around the implanted valve.

“Axpixaban after a TAVI procedure is not superior to standard of care antithrombotic treatment in terms of net clinical benefit, globally and in each stratum,” concluded the investigative team.

The study, “Oral Anti-xa Anticoagulation After Trans-aortic Valve Implantation For Aortic Stenosis: The Randomized Atlantis Trial,” was presented at ACC 2021.