ATLANTIS Evaluates Apixaban Versus Standard Care After TAVR

May 15, 2021—The blood thinner apixaban was not superior to standard of care following transcatheter aortic valve replacement (TAVR), according to findings from the ATLANTIS trial. Investigators found that apixaban reduced the formation of thrombosis around the implanted valve with no increased bleeding risk. However, a subset of patients taking apixaban who did not have an indication for anticoagulation apart from the TAVR procedure showed a tendency toward a higher rate of non-cardiovascular death. This observation deserves further exploration, advised the ATLANTIS investigators.

An announcement of the findings from the American College of Cardiology (ACC) noted that apixaban is a nonvitamin-K antagonist blood thinner that has demonstrated better net clinical benefit than vitamin K antagonists (VKA) like warfarin and antiplatelet drugs in some patients with atrial fibrillation (AFib). The ATLANTIS trial tested whether apixaban was superior to standard of care antithrombotic treatment, comprising either VKA or aspirin, after successful TAVR. The trial was conducted by the Allies in Cardiovascular Trials Initiatives and Organized Networks—the ACTION Group.

Jean-Philippe Collet, MD, presented the ATLANTIS study virtually at the ACC 70th Annual Scientific Session.

“Our results do not suggest we can routinely use apixaban as the default antithrombotic treatment after successful TAVR,” commented Dr. Collet in the ACC press release. “Although the safety of apixaban is the same as standard care and it better prevents valve thrombosis, we observed an unexplained signal on noncardiovascular 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.” Dr. Collet is Professor of Medicine and interventional cardiologist at Groupe Hospitalier Pitié-Salpêtrière in Paris, France.

According to ACC, the ATLANTIS trial investigators enrolled 1,510 patients at 50 centers in four countries who underwent a successful TAVR procedure between 2016 and 2019. Approximately one-third of the patients required anticoagulation therapy for reasons other than the TAVR procedure, mainly for AFib. Half of this group and half of the remaining patients were randomly assigned to receive apixaban. The remaining patients received standard care, which consisted of the VKA warfarin in patients requiring anticoagulation and an antiplatelet medication alone (typically aspirin) in those not requiring anticoagulation.

At 1 year, the investigators 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. The endpoint occurred in 18.4% of patients taking apixaban and 20.1% of patients assigned to standard care. Using 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 to the standard care group, reported the ATLANTIS investigators.

“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 noncardiovascular death,” advised Dr. Collet in the ACC press release. “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.”

The ACC announcement noted that the investigators used four-dimensional CT scans to examine the implanted valve and assess any evidence of thrombosis more closely. They found that study patients 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.

The investigators advised that the signal on noncardiovascular 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.

Dr. Collet said that the absolute number of noncardiovascular 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. “We cannot exclude a play of chance,” noted Dr. Collet in the ACC announcement.