A direct oral anticoagulant (DOAC) was no better than existing antithrombotic treatments after transcatheter aortic valve replacement (TAVR), according to ATLANTIS trial investigators.
TAVR patients randomized to apixaban (Eliquis) instead of antiplatelet therapy or warfarin saw no reduction in the trial’s primary endpoint, a composite of death, MI, stroke, systemic emboli, intracardiac or bioprosthesis thrombus, episode of deep vein thrombosis (DVT) or pulmonary embolism (PE), and major bleeding over 1-year follow-up (18.4% vs 20.1%, HR 0.92, 95% CI 0.73-1.16).
These findings were consistent whether patients had an indication for oral anticoagulation or not, reported Jean-Philippe Collet, MD, PhD, of Pitié-Salpêtrière Hospital in Paris, at the American College of Cardiology (ACC) virtual meeting.
“The most appropriate antithrombotic therapy after TAVR remains uncertain. ‘Standard of care’ has not been standardized, although most patients are treated as in the control group in this trial with antiplatelet therapy, unless there is an indication for full anticoagulation, such as in patients with atrial fibrillation,” according to Robert Bonow, MD, of Northwestern University Feinberg School of Medicine in Chicago, who was not involved with the study.
“This trial provides important new information on use of DOACs after TAVR, but is unlikely to change practice,” he stated.
For now, valve thrombosis appears to be fairly common after TAVR but not associated with clinical events.
“There’s no evidence that anything other than aspirin is beneficial to these patients,” concluded ACC panelist Michael Mack, MD, of Baylor Scott & White Health System in Plano, Texas.
Previously, POPular TAVI investigators had reported that TAVR patients not requiring anticoagulation had worse outcomes when given dual antiplatelet therapy instead of aspirin alone.
Before that, harm had been suggested with low-dose rivaroxaban (Xarelto) compared with antiplatelet therapy after TAVR in the GALILEO trial. That study was terminated early due to safety reasons, namely increases in major adverse cardiovascular events and major bleeding among rivaroxaban users who did not have an indication for anticoagulation.
Now, the ATLANTIS trial shows that people without a need for oral anticoagulation who took apixaban showed significantly higher rates of non-cardiovascular death (2.66% vs 0.96%, HR 2.99, 95% CI 1.07-8.35).
“As expected, apixaban was more effective than antiplatelet therapy in reducing valve thrombosis in those without an indication for anticoagulation, but this came at the price of higher rates of the combined endpoint of death, stroke, and systemic embolism,” Bonow observed. “Assuming that apixaban did not increase embolism, these results are driven by higher rates of death or stroke, which is supported by the finding of increased non-cardiovascular death.”
ATLANTIS was an open-label, phase III trial conducted in Europe. Collet and colleagues randomized 1,510 people who had received successful TAVR for aortic stenosis to apixaban 5 mg twice a day (2.5 mg twice a day under certain criteria) or standard of care (single or dual antiplatelet therapy or warfarin).
The cohort had a mean age of 82, and about 47% were men. Average STS risk score was 5.14%.
Participants were roughly split between those getting self-expanding TAVR valves and those getting balloon-expandable devices.
Not counting valve thrombosis in the primary endpoint did not tilt the result in favor of the DOAC or standard of care groups (17.8% vs 16.1%, HR 1.12, 95% CI 0.88-1.44), according to a post hoc sensitivity analysis.
However, apixaban reduced the individual endpoints of bioprosthetic thrombosis (1.1% vs 4.7%, HR 0.23, 95% CI 0.11-0.50) and DVT or PE (0.1% vs 1.5%, HR 0.09, 95% CI 0.01-0.72).
A safety analysis showed no uptick in major, minor, or any bleeding in general when patients were given apixaban instead of warfarin or antiplatelets.
The investigators acknowledged that their open-label trial was subject to reporting and ascertainment biases, though outcomes had been prespecified and adjudicated by an independent, blinded clinical events committee.
Longer follow-up of these patients is also needed, suggested ACC session chair Valentin Fuster, MD, PhD, of Mount Sinai Hospital in New York City.
ATLANTIS was supported by Assistance Publique des Hôpitaux de Paris and funded by ACTION fonds and Alliance BMS/Pfizer.
Collet disclosed relevant relationships with AstraZeneca, Bayer, Bristol Myers Squibb, and Medtronic.
Mack disclosed relevant relationships with, and/or support from Gore, Carmat, Abbott Vascular, Edwards Lifesciences, and Medtronic.
Fuster reported no relevant relationships with industry.