Subclinical valve thrombosis after transcatheter aortic valve intervention (TAVI) has emerged as a challenge to the standardization of antithrombotic therapy after valve implantation. Results of the randomized ATLANTIS trial, presented also today, May 15, as a Late Breaking Clinical Trial at ACC 2021, showed no superiority of apixaban over standard of care after transcatheter aortic valve intervention, irrespective of the baseline need for anticoagulants. In his Focused Clinical Research Session, Gilles Montalescot, MD, PhD, Professor of Cardiology at the Pitié-Salpêtrière Hospital, Paris, presented the 4D-CT substudy results to assess the incidence and implications of CT-proven valve thrombosis.
This substudy was mandated as part of the original study protocol. Of the 1500 patients assigned to the treatment group, 762 had CT scans complete for all desired endpoints, 370 of whom were in the apixaban arm and 392 of whom were in the standard of care arm. The primary outcome of Grade 3 or 4 restricted leaflet motion (RLM) or Grade 3 or 4 hypoattenuation leaflet thickening (HALT) was seen in 8.9% of patients taking apixaban versus 13% in those undergoing standard of care (OR 0.65, 95% CI 0.41-1.04), P=0.0375. The difference was starker when apixaban was compared to antiplatelet therapy alone in those without an indication for oral anticoagulation, with an event rate of 8.7% versus 15.9% (OR 0.51, 95% CI 0.3-0.86). With respect to the primary outcome, there was no difference between apixaban and warfarin.
Given concern for the link between RLM, HALT and ischemic stroke, the investigators sought to assess the incidence of stroke with respect to their CT findings. While those with RLM and HALT had numerically higher rates of stroke at one year (10.7% vs 7.1%), the difference did not meet statistical significance (HR 1.68, 95% CI 0.82-3.44).
After the presentation, Dr. David Cohen of St. Francis Hospital, questioned the need for continued examination of subclinical valve thrombosis in trials, given the unknown clinical benefit. “It is too early to tell,” replied Dr. Montalescot, and then added, “Valve thrombosis may have an impact on the durability of these valves, which has been seen in surgical valves. We need to accumulate data on valve thrombosis in TAVI and long-term follow up after a year.” Both physicians agreed that the mortality signal seen in ATLANTIS and GALILEO in patients without an indication for oral anticoagulation are concerning but need to be taken in the context of patients’ causes of death, which were almost always due to noncardiac causes.
While this substudy was limited by its short-term, follow up of 1 year duration, it adds to the growing body of evidence for oral anticoagulants in the prevention of subclinical valve thrombosis, the implications of which are yet to be defined.