Introduction and methods

Oral Anti-Xa Anticoagulation After Trans-aortic Valve Implantation For Aortic Stenosis: The Randomized ATLANTIS Trial

Presented at ACC.21 by Jean-Philippe Collet, MD, PhD (Paris, France)

Thrombotic and bleeding events after Transcatheter Aortic Valve Implantation (TAVI) are frequent and have a negative effect on short-term survival. The best strategy to prevent these complications is not completely clear. The ATLANTIS trial aimed to investigate whether apixaban was superior compared to standard-of-care after successful TAVI.

ATLANTIS was an international, randomized, open-label phase 3 trial which was conducted at 50 centers in four countries (France, Germany, Italy and Spain) and enrolled a total of 1510 patients. Patients who underwent a successful TAVI procedure were stratified according to the presence or absence of an indication other than the TAVI procedure for oral anticoagulation. In stratum 1, 451 patients with an indication for anticoagulation other than the TAVI procedure, were randomized 1:1 to receive either VKA or apixaban. In stratum 2, 1049 patients with no indication for anticoagulation other than the TAVI procedure, were randomized 1:1 to receive DAPT/SAPT or apixaban. A total of 749 patients received apixaban and 751 patients received standard-of-care. Patients in the apixaban arms received apixaban 5 mg bid, or apixaban 2.5 mg bid according to the drug label or when it was combined with antiplatelet therapy. The primary endpoint was a composite of death, MI, stroke, systemic emboli, intracardiac or bioprosthesis thrombus, episode of DVT or pulmonary embolism, major bleedings over one year follow-up. The primary safety outcome was defined as life-threatening (including fatal), disabling or major bleeding.

Main results

• There was no superiority of apixaban over standard-of-care for the primary endpoint (total population; HR 0.92, 95%CI 0.73-1.16). In addition, there was no interaction according to the indication for anticoagulation other than the TAVI procedure (stratum 1: HR 1.02, 95%CI 0.68-1.51; stratum 2: HR 0.88, 95%CI 0.66-1.17; P for interaction=0.57).
• There was no significant difference in the primary safety outcome between the apixaban arm and standard-of-care arm (HR 1.02, 95%CI 0.72-1.44).
• Outcomes according to the 2 different strata were investigated in post-hoc analyses. In patients with an indication for anticoagulation other than the TAVI procedure (stratum 1), there was no difference in any of the efficacy and safety outcomes between the apixaban arm and standard-of-care arm.
• In stratum 2, there were numerically higher numbers of secondary outcomes in the apixaban arm compared to the standard-of-care arm. This difference was not driven by an increase in MI or stroke events, but primarily by a higher number of non-CV deaths in the apixaban arm compared to the standard-of-care arm (non-CV death: HR 2.99, 95%CI 1.07-8.35). Any valve thrombosis was reduced in the apixaban group vs. standard-of-care group in stratum 2 (HR 0.19, 95%CI 0.08-0.47). These post-hoc analyses were exploratory with no statistical analysis, as there was no significant difference between groups with respect to the primary endpoint.

Conclusion

Treatment with apixaban following a successful TAVI procedure was not superior to standard-of-care in terms of net clinical benefit in the total study population and in each stratum (according to the presence or absence of an indication other than the TAVI procedure for oral anticoagulation). There was no significant difference in the primary safety outcome between the apixaban group and standard-of-care group. Exploratory post-hoc analyses showed a reduction in subclinical valve thrombosis in patients without an indication for anticoagulation other that the TAVI procedure. However, non-CV mortality was increased in the stratum of patients without an indication for anticoagulation other that the TAVI procedure.

Discussion

The discussant Jane Linderbaum (Rochester, MN, USA) said that although apixaban was not superior to standard-of-care after TAVI, and bleeding outcomes were similar between groups, the signal of reduced subclincal valve thrombosis is very interesting. It will be interesting to follow these groups of patients for a longer time period to gain additional insights in where apixaban may provide benefit.

-Our coverage of ACC.21 is based on the information provided during the congress –