Physicians' Academy for Cardiovascular Education

DOAC vs. standard of care after TAVR: risk of valve thrombosis and clinical outcomes

Apixaban and Valve Thrombosis After Transcatheter Aortic Valve Replacement: The ATLANTIS-4D-CT Randomized Clinical Trial Substudy

Literature - Montalescot G, Redheuil A, Vincent F, et al. - JACC Cardiovasc Interv. 2022 Sep 26;15(18):1794-1804. doi: 10.1016/j.jcin.2022.07.014

Introduction and methods


Transcatheter aortic valve replacement (TAVR) is possibly associated with subclinical leaflet thrombosis of the implanted bioprosthetic aortic valves, with or without valve dysfunction [1-3]. Furthermore, this early valve thrombosis could be linked to the occurrence of thromboembolic events, such as ischemic stroke, after TAVR [2-5]. Previous analyses have indicated that oral anticoagulation (OAC ) therapy perhaps prevents subclinical leaflet thrombosis [2,6,7].

Aim of the study

The study aims were to examine: (1) the incidence of subclinical obstructive valve thrombosis 90 days after successful TAVR; (2) the relationship between valve thrombosis and clinical outcomes at 1 year; and (3) the effect of anticoagulation with apixaban versus current standard of care on the occurrence of valve thrombosis (and to determine whether there was an interaction according to OAC indication status).


This was a prespecified substudy of the international, randomized, open-label, superiority, phase 3 ATLANTIS (Anti-Thrombotic Strategy to Lower All Cardiovascular and Neurologic Ischemic and Hemorrhagic Events After Trans-Aortic Valve Implantation for Aortic Stenosis) trial. Previously, this trial showed that apixaban 5 mg twice daily was not superior to standard of care (i.e., VKA or antiplatelet therapy, depending on OAC indication) after successful TAVR [8]. In addition, apixaban treatment was associated with similar safety but also with more non–CV deaths compared with standard of care [8].

To detect subclinical valve thrombosis, all randomized patients in the main ATLANTIS trial (i.e., intention-to-treat population) were offered dynamic cardiac 4-dimensional (4D) CT, 3–6 months after randomization. The 4D-CT images were assessed for the presence of valvular thrombosis and leaflet motion. In total, 762 patients were included in the ATLANTIS-4D-CT substudy, of whom 370 received apixaban and 392 received standard of care. There was no specific power calculation for the substudy.


The primary endpoint was the presence of subclinical valve thrombosis, which was defined as ≥1 prosthetic valve leaflet with reduced leaflet motion (RLM) of grade 3 or 4 (on a 5-point scale) or hypoattenuated leaflet thickening (HALT) of grade 3 or 4 (on a 5-point scale), 90 days after TAVR. Secondary endpoints included the percentage of patients with thrombi.

The authors defined 2 composite ischemic event endpoints: (1) death, MI, stroke, or peripheral embolism and (2) death, MI, or any stroke/TIA, both assessed at 1 year. The number of bleeding events (including any bleeding and life-threatening bleeding) was also determined.

Main results

Incidence of subclinical valve thrombosis

Clinical outcomes


In this substudy of the ATLANTIS trial, apixaban reduced the risk of subclinical valve thrombosis 90 days after successful TAVR compared with antiplatelet therapy in patients who did not have an OAC indication. However, this coincided with a nonsignificant higher rate of thromboembolic and bleeding events 1 year after the procedure. There was no benefit of apixaban over VKA therapy. As apixaban was overall not superior to standard of care in the main ATLANTIS trial, the authors warn that the results of this substudy should be interpreted with caution.


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Find this article online at JACC Cardiovasc Interv.

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