No go (again) for oral anticoagulation after TAVR: Results of the ADAPT-TAVR trial
Reported from ACC 2022
Francesco Costa analyses the results of ADAPT-TAVR, a prospective randomized trial on edoxaban vs dual antiplatelet therapy for valve thrombosis and cerebral thromboembolism after transcatheter aortic-valve replacement.
There is still discussion regarding the optimal antithrombotic therapy after transcatheter aortic valve replacement (TAVR). The main rationale for antithrombotic therapy after TAVR is two-fold: first to minimize the risk of stroke and embolic complications, which is higher early after the procedure, and secondly, to reduce the risk of clinically evident or subclinical valve thrombosis.
Most centres worldwide assign single or dual antiplatelet therapy after TAVR based on prior randomized clinical trials, yet the role of oral anticoagulation in patients without other concomitant indications to this treatment (e.g. atrial fibrillation) is still debated.
The ADAPT-TAVR Trial was a prospective randomized trial conducted at 5 centres in Asia with the objective to evaluate the impact of oral anticoagulation vs. dual antiplatelet therapy for the prevention of leaflet thrombosis, and the related impact of these imaging findings on neurological imaging and clinical assessment scales.
A total of 229 patients have been randomized to oral anticoagulation with Edoxaban 60mg (or 30mg if clinically indicated) or dual antiplatelet therapy with aspirin and clopidogrel. Established indications of oral anticoagulation (e.g. atrial fibrillation) were a study exclusion criteria.
The study's primary endpoint was the incidence of leaflet thrombosis on 4D, volume-rendered CT at 6 months, while secondary endpoints included number/volume of new cerebral lesions on brain MRI and a series of neurological/neurocognitive assessments.
The study finally showed no difference in the ITT analysis between oral anticoagulation with edoxaban and DAPT, with a non-significant trend towards reduction (8.5% difference; risk ratio of 0.53) of leaflet thrombosis with edoxaban. With respect to the neurological imaging and scales evaluated, edoxaban was not found superior to DAPT in any of the explored endpoints, including the number of new cerebral lesions, volume of new lesions, NHISS scale, modified Rankin scale or Montreal cognitive assessment scale. There was no association between subclinical leaflet thrombosis and new cerebral thromboembolic lesions and changes in neurological assessment scales.
The prior GALILEO 4D trial observed that rivaroxaban was more effective than antiplatelet therapy in preventing subclinical leaflet-motion abnormalities. Similar results were observed in the ATLANTIS trial that observed a lower rate of valve thrombosis with apixaban compared to antiplatelet therapy. Yet from a clinical standpoint, neither ATLANTIS nor GALILEO trial showed a benefit of oral anticoagulation in patients after TAVR, and in GALILEO rivaroxaban was associated with a higher risk of death or thromboembolic complications compared to antiplatelet therapy.
Similarly, the current ADAPT-TAVR trial, which was not powered to explore clinically meaningful hard endpoints, did not find any clinical advantage of oral anticoagulation and no impact of subclinical valve thrombosis with respect to the explored neurological imaging and clinical assessment scales.
So after three randomized trials, there is still no evidence that oral anticoagulation, in patients without any additional indication for it, is beneficial after TAVR.
Importantly, clinical implications of leaflet thrombosis have not been yet confirmed, and this imaging phenomenon should not prompt antithrombotic therapy for its prevention or routine screening with 4D-CT scan after TAVR. In addition, while prior meta-analysis suggested that treating subclinical valve thrombosis is associated with a reduction of MACE and cerebral ischemic events, no prospective randomized trial demonstrated a clinical benefit of routine treatment of subclinical valve thrombosis.
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