The administration of apixaban monotherapy after transcatheter aortic valve replacement is not superior to the standard of the care antithrombotic treatment, results of the randomized, phase IIIb, prospective, open label, ATLANTIS trial, Anti-Thrombotic Strategy After Trans-Aortic Valve Implantation for Aortic Stenosis (NCT02664649), show. These findings hold true regardless of a patient’s baseline requirement for anticoagulation.
The need for antithrombotic therapy after TAVR has moved in several directions, with evidence that single antiplatelet therapy is safer than dual antiplatelet therapy, and a vitamin K antagonist alone is safer than when combined with antiplatelet therapy. After GALILEO last year demonstrated more harm with low dose rivaroxaban after TAVR, the world waited in anticipation to see if a single oral anticoagulant agent could be proven safe and effective. In a Late Breaking Clinical Trial session at the American College of Cardiology 2021 Scientific Sessions, May 15, Dr. Jean-Philippe Collet of Pitié-Salpêtrière Hospital, Paris, presented the findings of the anticipated randomized ATLANTIS trial, which assessed the safety and efficacy of apixaban after successful TAVR.
The investigators studied 1510 participants, categorized into strata: those with a baseline indication for anticoagulation, and those without one. Apixaban was studied in a 1:1 fashion against vitamin K antagonists for those with an indication for oral anticoagulation, and against dual or single antiplatelet therapy for those without an indication. Participants were followed for one year and assessed for a primary outcome composite of death, myocardial infarction, stroke, systemic emboli, intracardiac or bioprosthesis thrombus, and major bleeds. The average age was 82 years, and all patients were medium to high risk for surgical aortic valve replacement. Of note, patients with recent acute coronary syndrome, stent implantation, or bleeding were excluded for the trial.
The primary outcome was seen in 18.4% of patients receiving apixaban, and 20.1% of patients in the standard of care arm, which did not reach significance (HR 0.92, CI 0.73-1.16). After excluding valve thrombosis from the primary outcome, apixaban was shown to have numerically higher rates of death, MI, and stroke. However, with regard to subclinical valve thrombosis, apixaban did have fewer events when compared to standard of care (1.1% vs 4.7%; HR 0.23; 95% CI 0.11-0.50).
After the presentation, Dr. Collet stated that the main benefit of the study was in its showing that “Patients with an underlying need for anticoagulation would benefit similarly from warfarin or apixaban, because of its ease of use.” Dr. Michael Mack, medical director of cardiothoracic surgery at Baylor Scott &White Health, called the area of antithrombotic therapy after TAVR a “significant clinical conundrum.” In response to his concerns of the low incidence of subclinical valve thrombosis in the study, Dr. Collet stated that serial CT scans were likely to have shown higher rates of valve thrombosis, and that oral anticoagulants should be considered for patients who are at higher risk of developing thrombus, such as those undergoing valve-in-valve TAVI and those with small annuli.
The authors acknowledged several limitations of the trial, namely that this was an open-label trial, which subjects it to reporting and ascertainment bias. Furthermore, the results pertain only to those who underwent successful TAVI procedures in the absence of other valve procedures. Finally, the study was not designed to assess definitive conclusions on efficacy.