By Jeffrey Zimmet, MD, PhD
Associate Professor of Medicine, University of California, San Francisco; Director, Cardiac Catheterization Laboratory, San Francisco VA Medical Center
SYNOPSIS: In patients without an indication for anticoagulation undergoing transcatheter aortic valve replacement, treatment with edoxaban did not significantly affect the incidence of leaflet thrombosis as detected by CT scans.
SOURCE: Park DW, Ahn JM, Kang DY, et al. Edoxaban versus dual antiplatelet therapy for leaflet thrombosis and cerebral thromboembolism after TAVR: The ADAPT-TAVR randomized clinical trial. Circulation 2022; Apr 4. doi: 10.1161/CIRCULATIONAHA.122.059512. [Online ahead of print].
The ADAPT-TAVR trial was designed based on the hypothesis that the oral factor Xa inhibitor edoxaban would prevent subclinical leaflet thrombosis to a greater extent than antiplatelet therapy, and that this would result in a lower degree of cerebral embolization. The authors targeted a sample of 220 patients, ultimately enrolling 229 patients who were randomized in the first week after transcatheter aortic valve replacement (TAVR) to a six-month regimen of either usual-dose edoxaban or dual antiplatelet therapy (DAPT) with clopidogrel and aspirin.
The primary endpoint was the incidence of leaflet thrombosis on CT imaging at six months after TAVR. Brain MRI was performed in the week following TAVR and again at six months. Important secondary endpoints included the occurrence of new lesions on MRI as well as the change in neurologic and neurocognitive function between the immediate post-TAVR period and the six-month checkup. Enrolled patients were a mean age of 80.1 years, and 58% were women. A total of 61.3% of the anticoagulant group received the lower dose of 30 mg edoxaban, based on established criteria for dose adjustment.
For the primary endpoint, 10 of 102 of patients in the edoxaban group showed evidence of leaflet thrombosis at six months vs. 20 of 109 of the DAPT group. This difference did not meet statistical significance (P = 0.076). Likewise, there was no significant difference in the incidence of new lesions on MRI, with 25% of patients showing this finding in the edoxaban group and 20.2% in the DAPT group. Only two patients in each group experienced clinically evident stroke.
Neurologic function as measured by the NIH Stroke Scale worsened to a similar degree between groups over the trial period. The percentage of patients with worsened neurocognitive function, as measured by the Montreal Cognitive Assessment, also was similar between patient sets (30% of the edoxaban group, 22.2% of the DAPT group). Importantly, comparisons of patients with and without valve leaflet thrombosis and reduced leaflet motion did not reveal any correlation with number of new cerebral lesions on MRI or measurements of decline in neurological function.
The authors concluded edoxaban led to a numerically lower incidence of leaflet thrombosis in post-TAVR patients that was not statistically significant vs. DAPT. Further, measures of cerebral lesions and neurological and neurocognitive function also did not change significantly. The authors cautioned the study was underpowered for clinical events.
COMMENTARY
Perhaps the most surprising finding in this study was the measured reduction in incidence of subclinical leaflet thrombosis (SLT) with edoxaban did not reach statistical significance, although the trend was in a consistent direction with every CT measure of thrombosis. The imaging substudy of the GALILEO trial did show a decrease in SLT with rivaroxaban, although the main study revealed an increase in the risk of death, thromboembolic events, and bleeding vs. antiplatelet therapy.
The fact anticoagulation did not lead to a reduction in the incidence of new cerebral lesions — the trend here was in the opposite direction — is an important one. Park et al went a step further, showing no demonstrable relationship between the imaging finding of SLT and either new brain lesions or measurements of neurologic function. This finding should convince clinicians that routine imaging to look for SLT is not indicated. Routine transthoracic echocardiography remains indicated in the post-TAVR patient, but further imaging by CT is not required in the absence of an unexplained increase in transvalvular gradient or other evidence of valve dysfunction.
Finally, we should note the comparator in these trials — DAPT — represents a holdover from early TAVR practice. Randomized trials, including POPular TAVI and ARTE, have shown more bleeding rather than benefit from dual vs. single antiplatelet therapy after TAVR.1,2 More work will be required to define the optimal regimen for TAVR patients without an indication for anticoagulation.
REFERENCES
- Nijenhuis VJ, Brouwer J, Delewi R, et al. Anticoagulation with or without clopidogrel after transcatheter aortic-valve implantation. N Engl J Med 2020;382:1696-1707.
- Rodés-Cabau J, Masson JB, Welsh RC, et al. Aspirin versus aspirin plus clopidogrel as antithrombotic treatment following transcatheter aortic valve replacement with a balloon-expandable valve: The ARTE (aspirin versus aspirin + clopidogrel following transcatheter aortic valve implantation) randomized clinical trial. JACC Cardiovasc Interv 2017;10:1357-1365.
In patients without an indication for anticoagulation undergoing transcatheter aortic valve replacement, treatment with edoxaban did not significantly affect the incidence of leaflet thrombosis as detected by CT scans.
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