Edoxaban Versus Dual Antiplatelet Therapy for Leaflet Thrombosis and Cerebral Thromboembolism After TAVR: The ADAPT-TAVR Randomized Clinical Trial

Abstract

Background: It is unknown whether direct oral anticoagulant edoxaban can reduce leaflet thrombosis and the accompanying cerebral thromboembolic risk after transcatheter aortic-valve replacement (TAVR). Also, the causal relationship of subclinical leaflet thrombosis with cerebral thromboembolism and neurological or neurocognitive dysfunction remains unclear. Methods: We conducted a multicenter, open-label randomized trial comparing edoxaban with dual antiplatelet therapy (DAPT; aspirin plus clopidogrel) in patients who had undergone successful TAVR and did not have an indication for anticoagulation. The primary end point was an incidence of leaflet thrombosis on four-dimensional computed tomography (CT) at 6-month. Key secondary end points were the number and volume of new cerebral lesions on brain magnetic resonance imaging (MRI) and the serial changes of neurological and neurocognitive function between 6-month and immediate post-TAVR. Results: A total of 229 patients were included in the final intention-to-treat population. There was a trend toward a lower incidence of leaflet thrombosis in the edoxaban group than in the DAPT group (9.8% vs. 18.4%; absolute difference, −8.5%; 95% confidence interval [CI], −17.8% to 0.8%; P=0.076). The percentage of patients with new cerebral lesions on brain MRI (edoxaban vs. DAPT; 25.0% vs. 20.2%; difference, 4.8%; 95% CI, −6.4% to 16.0%) and median total new lesion number and volume were not different between two groups. Also, the percentages of patients with worsening of neurological and neurocognitive function were not different among the groups. The incidence of any or major bleeding events were not different between two groups. We found no significant association of the presence or extent of leaflet thrombosis with new cerebral lesions and a change of neurological or neurocognitive function. Conclusions: In patients without an indication for long-term anticoagulation after successful TAVR, the incidence of leaflet thrombosis was numerically lower with edoxaban than with DAPT, but this was not statistically significant. The effect on new cerebral thromboembolism and neurological or neurocognitive function were also not different between two groups. Because the study was underpowered, the results should be considered hypothesis-generating, highlighting the need for further research.

A 20-year journey in transcatheter aortic valve implantation: Evolution to current eminence

“…Finally, in the ADAPT-TAVR study with 229 patients undergoing TAVI and without any indications for anticoagulation, edoxaban resulted in numerically twofold lower subclinical THV leaflet thrombosis at 6 months (9.8 vs. 18.4%). However, the rates of death, stroke, transient ischemic attack, blood clotting in the brain and neurocognitive dysfunction were not different between the groups ( 158 ). Until further long-term follow-up results become available to further elucidate whether the reduction of THV thrombosis with oral anticoagulation will eventually be translated to overt clinical benefits, the primary antithrombotic therapy unless there is another indication for oral anticoagulation should include a single antiplatelet regimen with aspirin or clopidogrel.…”

Stroke prevention during and after transcatheter aortic valve implantation: From cerebral protection devices to antithrombotic management

“…The ADAPT-TAVR ( n = 229) was an open-label trial that evaluated the use of edoxaban for 6 months or DAPT with ASA plus clopidogrel on leaflet thrombosis assessed by 4DCT in patients without indication of OAC. At 6 months after TAVI, the researchers noted no link between subclinical leaflet thrombosis and an increased risk of cerebral thromboembolism or neurological impairment ( 52 ). Also, no statistically significant difference between edoxaban and DAPT in leaflet thrombosis incidents were found, although edoxaban group patients did show a lower trend (9.8 vs. 18.4% for DAPT; absolute difference: −8.5%; 95% CI: −17.8 to 0.8%; p = 0.076).…”

Orale Antikoagulation nach Klappeneingriffen – Was ist der Standard?

“…Konsistent hierzu war in ATLANTIS die Rate an HALT/RLM in der Apixaban-gegenüber der antithrombozytären Gruppe reduziert, bei jedoch erhöhter Gesamtmortalität [11]. Die ebenfalls kürzlich erschienene ADAPT-TAVR-Studie (229 Patienten) ging hier noch einen Schritt weiter: Hier wurde Edoxaban mit einer dualen antithrombozytären Therapie nicht nur hinsichtlich des Auftretens von HALT/RLM (primärer Endpunkt), sondern auch bezüglich der zerebralen ischämischen Ereignisrate (mittels systematischer MRT-Untersuchungen, sekundärer Endpunkt) verglichen [39]. Edoxaban führte hier zu einer statistisch nicht signifikanten Reduktion subklinischer Klappenthrombosen (9,8% vs. 18,4%).…”

“…Hinsichtlich klinischer Endpunkte wie Blutung und embolischer Ereignisse ergaben sich keine Unterschiededie Studie war hierfür aber weder ausgelegt noch ausreichend gepowert. Interessant war jedoch auch hier, dass sich keine eindeutige Assoziation zwischen dem Auftreten oder der Ausprägung von thrombotischen Auflagerungen und zerebralen Läsionen in der MRT zeigte [39]. Somit bleibt unklar, ob die Detektion von HALT/RLM zu einer Anpassung der antithrombotischen Therapie nach TAVI führen sollte, um embolische Ereignisse und eine möglicherweise beschleunigte Degeneration der TAVI-Prothese zu verhindern.…”