Apixaban and Valve Thrombosis after TAVR

TAVR has been associated with early valve thrombosis, characterized by thrombus formation in the prosthetic valve with or without valve dysfunction. This dysfunction is related to leaflet thickening and reduced motion, reduced effective orifice area, or increased transvalvular gradient. A multidetector CT scan allows the dynamic assessment of valves and ruling out fibrosis vs. thrombosis.

Subclinical thrombosis by CT is characterized as hypoattenuated leaflet thickening (HALT) and reduced leaflet motion (RLM) which can be identified in up to 10% to 30% of patients. Some studies have linked subclinical valve thrombosis to thromboembolic events. Two registries, the GALILEO (Global Study Comparing a Rivaroxaban-Based Antithrombotic Strategy to an Antiplatelet-Based Strategy After Transcatheter Aortic Valve Replacement to Optimize Clinical Outcomes) and the ATLANTIS (Anti-Thrombotic Strategy to Lower All Cardiovascular and Neurologic Ischemic and Hemorrhagic Events after Trans-Aortic Valve Replacement for Aortic Stenosis), have suggested the potential use of anticoagulation to prevent subclinical thrombosis.

The multicenter, randomized study ATLANTIS compared apixaban vs standard treatment after TAVR. The aim of this sub-study ATLANTIS-4D-CT was to assess the incidence of subclinical thrombosis at 90 days, its association to clinical events at 1 year and the effect of treatment.

Primary end point was the presence of at least one valve with grade III or IV reduced motion, defined as moderate and severe dysfunction (51-70% or >70% motion reduction); and grade III or IV leaflet thickness. Secondary end point was the presence of thrombi in the valve area measured by planimetry, in addition to ischemic events at one year.

762 patients undergoing 4D CT were looked at; 370 were randomized to Apixaban and 392 to standard treatment. Mean age was 82 and they were mostly women.

Primary end point occurred in 13% of patients in the standard treatment group vs 8.9% in the Apixaban group. The percentage of patients with marked dysfunction was significantly lower with Apixaban (1.4%) vs. standard treatment (7.1%) (OR: 0.18; 95% CI: 0.07-0.42). The use of Apixaban reduced grade III or IV RLM or HALT by 49% vs. antiplatelet treatment in patients with no indication of anticoagulation (OR: 0.51; 95% CI: 0.30-0.86; P= 0.01), while there were no differences in patients with anticoagulation indication. Neither were there differences in secondary end point.

Conclusion

The use of Apixaban as antithrombotic strategy after TAVR reduced valve thrombosis risk in patients with and without long term anticoagulation indication with no increase in thromboembolic or bleeding events. These results must be interpreted with caution given the sub-study design. The use of low doses of Apixaban in low risk populations requires further research.