In patients undergoing transcatheter aortic valve replacement (TAVR), the incidence of leaflet thrombosis was numerically lower in those treated with the anticoagulant edoxaban for 6 months after the procedure than in those who received dual antiplatelet therapy, although the difference was not statistically significant, in the ADAPT-TAVR study.
There was no difference in new cerebral thromboembolism or neurologic/neurocognitive function between the two groups in the study.
Also, there was no significant relation between subclinical leaflet thrombosis and increased risk for cerebral thromboembolism and neurologic dysfunction.
The ADAPT-TAVR trial was presented April 4 at the American College of Cardiology (ACC) 2022 Scientific Session by Duk-Woo Park, MD, Asan Medical Center, Seoul, South Korea. It was simultaneously published online in Circulation.
Dr. Duk-Woo Park
“The key messages from this study are that subclinical leaflet thrombosis has not been proven to affect clinical outcomes for patients undergoing valve replacement and that in patients in whom leaflet thrombosis causes no symptoms or complications, its presence should not dictate the type of antithrombotic therapy that patients receive following the implantation of an artificial heart valve,” Dr. Park said.
“These findings do not support the routine use of computed tomography scans to detect subclinical leaflet thrombosis,” he added.
Commenting on the study at an ACC press conference, Megan Coylewright, MD, director of the Structural Heart Program at Erlanger Health System, Chattanooga, Tennessee, said: “Oftentimes when studies are negative, we’re disappointed. In this case, I think we are pleased that the study is negative because it suggests we do not have to expose our TAVR patients to anticoagulation for benefit.”
Dr. Coylewright explained that the ADAPT-TAVR study was asking whether clots form on the valve, as defined by CT.
“We are worried about that for two reasons: could that clot cause a stroke, and could that clot cause the valve to break down over time. This study looked at the first issue. And it found that there was some clot build up on the valve, but that it wasn’t significantly different between the anticoagulant and dual antiplatelet groups. And there was no correlation with embolic events, she noted.
“It shows how fast our field moves. In the U.S. now, we are using aspirin alone at 81 mg for patients who do not have an indication for oral anticoagulation after TAVR. We are moving away from dual antiplatelet therapy because the bleeding risk is so bad,” Dr. Coylewright said.
In his presentation, Dr. Park explained that it is believed that oral anticoagulants are more effective than antiplatelet therapy at reducing subclinical leaflet thrombosis, but it is not known whether there is a causal association between subclinical leaflet thrombosis and cerebral embolism, or whether oral anticoagulation can reduce cerebral embolism related to subclinical leaflet thrombosis.
The ADAPT-TAVR was conducted to look at these issues. The open-label randomized trial was conducted in five centers in Hong Kong, South Korea, and Taiwan.
For the study, 229 patients who had undergone successful TAVR and did not have an indication for anticoagulation were randomized to edoxaban 60 mg once daily, edoxaban 30 mg once daily for patients needing a reduced dose, or dual antiplatelet therapy for 6 months.
The primary endpoint was an incidence of leaflet thrombosis on four-dimensional CT at 6 months.
Results showed a strong trend toward a lower incidence of leaflet thrombosis in the edoxaban groups than in the dual antiplatelet group (9.8% vs. 18.4%; P = .076).
There was a nonsignificant difference in the percentage of patients with new cerebral lesions identified on brain MRI between the edoxaban and dual antiplatelet groups (25.0% vs. 20.2%).
The percentage of patients with worsening of neurologic and neurocognitive function was not different among the groups.
The incidence of any or major bleeding events was not different between two therapies.
There was also no significant association of the presence or extent of leaflet thrombosis with new cerebral lesions or change of neurologic or neurocognitive function.
Dr. Park noted that the trial had several limitations, including an open-label design, use of surrogate imaging outcomes for the primary outcome, and the relatively short follow-up period, so the study was underpowered to detect any meaningful differences in clinical efficacy and safety outcomes. The results should thus be considered hypothesis-generating, highlighting the need for further research, he added.
The long-term effect of leaflet thrombosis or different antithrombotic strategies on bioprosthetic valve durability is still unknown, Dr. Park said.
He also pointed out that the findings cannot be directly extrapolated to patients with an established indication for oral anticoagulant therapy.
The ADAPT-TAVR trial was an investigator-initiated trial and was funded by the CardioVascular Research Foundation (Seoul, Korea) and Daiichi Sankyo Korea.