Compared with dual antiplatelet therapy (DAPT), direct oral anticoagulant (DOAC) monotherapy is associated with reduced risks of device-related thrombosis (DRT) and major bleeding within the first two to three months after left atrial appendage occlusion (LAAO), according to a meta-analysis of three small randomized controlled trials (RCTs) published Oct. 13 in EHJ.

Through a literature search, Ahmed Samy Badran, MBBCH, and Gregg W. Stone, MD, FACC, identified three RCTs that compared DOAC monotherapy with DAPT (aspirin and a P2Y₁₂ inhibitor) after LAAO: ADRIFT, ADALA and ANDES, with a total of 704 patients. In ADRIFT and ADALA, reduced-dose DOACs were used (rivaroxaban 10 or 15 mg qd and apixaban 2.5 mg bid, respectively), whereas standard 'atrial fibrillation (AFib) doses' of any of four DOACs were used in ANDES.

The studies were conducted across multiple centers in Europe and Canada, and the devices used were Watchman, Watchman FLX, Amulet and Lambre.

The primary endpoint was DRT, and additional outcomes included major and minor bleeding events, all-cause and cardiovascular mortality, and stroke/systemic embolism.

Participants had a mean age of 77 years and about two-thirds were men. They had substantial thromboembolic and bleeding risk, with mean CHA2DS2-VASc scores ranging from 4.0 to 4.7 and HAS-BLED scores ranging from 3.4 to 3.8. Prior bleeding was common (65-79%), more than 80% had hypertension and half had permanent AFib. The duration of the study drug treatment ranged from two months in one trial to three months in the other two trials.

Results of the analysis showed that DOAC monotherapy significantly reduced DRT risk (risk ratio [RR], 0.17, p=0.022; I²=0%) and major bleeding risk (RR, 0.51, p=0.045; I²=0%) when compared with DAPT. No significant differences between groups were observed for all-cause mortality, cardiovascular mortality, minor bleeding or stroke/systemic embolism.

"...our findings are most applicable to contemporary patients undergoing LAAO because of elevated bleeding risk and should be extrapolated cautiously to lower-risk populations," write Badran and Stone, noting that, given the relatively small size of the trials in the analysis, "larger trials are required to determine the optimal DOAC dose for this application."