ADAPT-TAVR Trial Evaluates Effects of Edoxaban on Thrombosis and Thromboembolism After TAVR

April 4, 2022—The American College of Cardiology (ACC) announced that data from the ADAPT-TAVR study demonstrated that patients treated with edoxaban for 6 months after a transcatheter aortic valve replacement (TAVR) experienced fewer symptomless blood clots inside the device than patients who were treated with two antiplatelet drugs.

However, the study found that compared with the patients in the antiplatelet therapy group, patients in the edoxaban group experienced no reduction in risk for strokes or transient ischemic attacks (TIAs), blood clots in the brain, or problems with thinking or memory during the 6 months after the valve replacement procedure.

The ADAPT-TAVR findings were presented by Principal Investigator Duk-Woo Park, MD, at ACC’s 71st annual scientific session, which was held April 2-4 in Washington DC. Dr. Park is with Asan Medical Center in Seoul, South Korea.

This study was simultaneously published online by Dr. Park et al in Circulation. The study was an investigator-initiated trial funded by the CardioVascular Research Foundation of Seoul, South Korea, and Daiichi Sankyo Korea (a subsidiary of the Japan-based maker of edoxaban).

According to the ACC press release, the study’s primary endpoint—the incidence of subclinical leaflet thrombosis (SLT) at 6 months after the valve replacement procedure—was lower in patients treated with edoxaban than in patient treated with dual antiplatelet therapy (DAPT), but it did not achieve statistical significance.

Additionally, Dr. Park reported that the trial failed to meet its secondary endpoint of a causative association of SLT with blood clotting in the brain and problems with thinking or memory.

In the ACC press release, Dr. Park commented, “The key messages from this study are that SLT has not been proven to affect clinical outcomes for patients undergoing valve replacement and that in patients in whom SLT 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. Additionally, these findings do not support the routine use of CT scans to detect SLT.”

At the time of enrollment in this study, most patients undergoing TAVR received treatment with DAPT (aspirin and clopidogrel) for 6 months postprocedure to reduce the risk of blood clots that can lead to a heart attack or stroke. Despite this drug therapy, however, some patients develop SLT that can be detected on a CT scan. Previous studies had suggested that as many as 38% of patients undergoing TAVR could develop SLT and that SLT might increase their risk for a stroke or TIA caused by a blood clot in the brain. Previous studies also suggested that treatment with a blood-thinning drug rather than DAPT after TAVR might reduce patients’ risk for a stroke or TIA.

Dr. Park noted that the ADAPT-TAVR study was designed to overcome the deficiencies of previous studies and resolve these uncertainties.

As summarized in the ACC press release, the study enrolled 229 patients (average age, 80 years; 58% women) who had undergone TAVR and did not have any heart conditions or other disorders that required long-term treatment with blood-thinning medications.

The patients were randomly assigned to receive either edoxaban or DAPT for 6 months. To detect blood clots in the brain or brain damage likely to cause problems with cognitive function, patients received MRI scans and tests of thinking and memory within 1 week of their TAVR procedure and again at 6 months. Approximately 95% of patients in the study completed all scans and cognitive function tests.

At the 6-month mark, patients received CT scans to detect SLT. Ten patients in the edoxaban group (9.8%) developed SLT that was detectable on the CT scan, compared with 20 patients in the DAPT group (18.4%); however, this difference was not statistically significant. Rates of death, stroke, TIA, blood clotting in the brain, and problems with thinking or memory were similar in the two groups.

“We saw no correlation between the number of occurrences of detectable SLT and the number of new signs of blood clotting in the brain or changes in cognitive function,” commented Dr. Park.

The study has several limitations, advised Dr. Park in the ACC press release. These limitations include that the study was not blinded; the number of patients enrolled was too small to identify any correlation between findings on MRI or CT scans and adverse events; and, the 6-month follow-up period was too short to determine the long-term effects of SLT or whether edoxaban or DAPT had any effect on the durability of a patient’s replacement heart valve. Dr. Park and his colleagues are planning future studies to address some of these questions, noted ACC.