Apixaban was not superior to standard of care following transcatheter aortic valve replacement (TAVR), according to findings from the ATLANTIS trial presented May 15 at ACC.21 during a Late-Breaking Clinical Trial session.

Researchers enrolled 1,510 patients at 50 centers in four countries (Spain, Italy, France and Germany) who underwent a successful TAVR procedure between 2016 and 2019. About one-third of the patients required anticoagulation therapy for reasons other than the TAVR procedure, mainly for atrial fibrillation (AFib). Half of this group and half of the remaining patients were randomly assigned to receive apixaban (5 mg bid). The remaining patients received standard care, which consisted of the vitamin K antagonist warfarin in patients requiring anticoagulation and an antiplatelet medication alone (typically aspirin) in those not requiring anticoagulation. 

At one year, the study found no significant difference in the primary endpoint, a composite of all-cause death, stroke, heart attack, valve thrombosis, pulmonary or systemic embolism, deep vein thrombosis or major bleeding, which occurred in 18.4% of those taking apixaban and 20.1% assigned to standard care.

According to statistical thresholds specified for the trial, these results show that apixaban was not superior to standard care in terms of the primary endpoint. In addition, there was no interaction according to the need for oral anticoagulation; however, there were numerically higher numbers of secondary endpoints including death, stroke, heart attack or systemic embolism in the apixaban group compared with the standard care group.

"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," said Jean-Philippe Collet, MD, the study's lead author. 

The researchers used 4D CT scans to examine the implanted valve and assess any evidence of thrombosis more closely. They found that participants taking apixaban had an 80% lower rate of clot formation around the implanted valve. In addition, patients with valve thrombosis had a higher rate of ischemic events.

"Our results do not suggest we can routinely use apixaban as the default antithrombotic treatment after successful TAVR," said Collet. "Although the safety of apixaban is the same as standard care and it better prevents valve thrombosis, we observed an unexplained signal on non-cardiovascular mortality among patients who do not need oral anticoagulation. In patients with an indication for oral anticoagulation, apixaban compares favorably with VKA on all endpoints and remains easier to use."

The signal on non-cardiovascular mortality reported in the subset of patients taking apixaban who did not require anticoagulation is consistent with findings from a previous trial, GALILEO, although the ATLANTIS trial did not find an excess of bleeds as was found in GALILEO, nor an excess of ischemic events. Collet said that the absolute number of non-cardiovascular deaths was low in the cohort without indication for anticoagulation, adding that these deaths were mainly due to sepsis or acute renal failure and were rarely preceded by minor bleeding events.

Clinical Topics: Anticoagulation Management, Cardiac Surgery, Heart Failure and Cardiomyopathies, Invasive Cardiovascular Angiography and Intervention, Valvular Heart Disease, Aortic Surgery, Cardiac Surgery and Heart Failure, Cardiac Surgery and VHD, Acute Heart Failure, Interventions and Imaging, Interventions and Structural Heart Disease, Angiography, Nuclear Imaging

Keywords: ACC Annual Scientific Session, ACC21, Aortic Valve, Aortic Valve Stenosis, Anticoagulants, Transcatheter Aortic Valve Replacement, Heart Failure, Heart Valve Diseases, Angiography

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