With Preliminary Win for DOAC, Sights Set on Supplanting DAPT After LAA Closure

PARIS -- In the first randomized trial of antithrombotic therapy after successful left atrial appendage (LAA) occlusion, low-dose apixaban (Eliquis) provided the better balance of thrombotic and bleeding events compared with dual antiplatelet therapy (DAPT).

The low-dose direct oral anticoagulant (DOAC) performed better in the 3-month primary endpoint counting thromboembolic events and device-related thrombosis (4.6% vs 21.7% with DAPT, HR 0.18, 95% CI 0.04-0.84), according to Xavier Freixa, MD, PhD, of the Hospital Clinic of Barcelona.

The stark difference was largely driven by device-related thrombosis (0% vs 8.7%, P=0.045) and was part of the reason that the ADALA trial was stopped earlier than anticipated, Freixa told the audience here at the EuroPCR meeting.

His group's original goal had been to enroll 160 participants, but an interim analysis led to abbreviated enrollment that stopped at 90 people -- 46 assigned to the DOAC and 44 to DAPT.

"It was a dilemma," Freixa said. "We ended up maybe sacrificing the number [of patients] but believing it was something good for the patients because we already had the result."

Also supporting the investigators' decision to halt enrollment was that the low-dose DOAC did not significantly triumph over DAPT for VARC-3 major bleeding at 3 months (4.6% vs 13.0%, HR 0.34, 95% CI 0.07-1.69), though the totality of bleeds, major and minor, pointed to a significant safety advantage with apixaban (4.6% vs 28.3%, HR 0.14, 95% CI 0.03-0.63).

With rigorous evidence lacking, DAPT with aspirin and clopidogrel (Plavix) for 1 to 3 months is currently the most accepted antithrombotic regimen after LAA closure. "There's no proof, no rationale, no evidence behind that," Freixa noted.

Based on the present findings, session panelist Francesco Saia, MD, of IRCCS University Hospital of Bologna, Italy, predicted that future guidelines might give a class I recommendation to low-dose DOACs and a weaker class III recommendation to DAPT after LAA occlusion.

"This is a beautiful trial, very interesting data, and this could change the guidelines ... With 90 patients, you're probably not going to do it," Saia cautioned.

Freixa agreed that future trials are needed and his group's study was just the first one. The findings await confirmation in the ongoing ANDES trial of 400 patients on different drugs and different doses, he said.

The ADALA investigators randomized patients approximately 4 hours after successful LAA occlusion. Treatment assignments were either low-dose DOAC (apixaban 2.5 mg twice a day) or standard DAPT for 3 months.

For the 90 participants, mean age was 76.6 years, and men accounted for two-thirds of the cohort. Freixa noted that this was a fairly standard LAA occlusion cohort, with 62% having permanent atrial fibrillation at baseline, an average CHA₂DS₂-VASc score of 4.0, and an average HAS-BLED score of 3.5.

Although the study authors aimed for an all-comers population, Freixa acknowledged that people at extreme bleeding risk (e.g., with a history of spontaneous intracranial bleeding) would not be considered candidates for anticoagulation and therefore were not included in the study.

Regarding the LAA occlusion procedure, the most popular device was the Amulet (67.8%), with a minority of patients getting the Watchman (23.3%) and the LAmbre (8.9%). The procedure took place at experienced centers, so there was a 100% success rate.

One case of major bleeding occurred in the DAPT arm within 7 days. There were no other serious adverse events (i.e., deaths, device embolization, ischemic stroke, cardiac tamponade, or vascular access complication) in either group.

Participants underwent transesophageal echocardiography and CT at 1 and 3 months to detect all device clots. Another imaging test is scheduled at the 1-year mark for this group, Freixa said.

Comment