Antithrombotic strategies and DOAC dosing following left atrial appendage occlusion: a network meta-analysis

Background/Introduction The optimal short-term antithrombotic strategy following left atrial appendage occlusion (LAAO) remains uncertain, with the need to balance thromboembolic prevention and bleeding risk presenting a critical challenge. Recent evidence suggests that direct oral anticoagulants (DOACs), may provide a favorable safety-efficacy profile, with low-dose regimens showing potential benefits during the device endothelialization period. Purpose This network meta-analysis (NMA) aimed to compare the efficacy and safety of various antithrombotic strategies, including DOAC dosing, following LAAO. Methods A systematic review and NMA were conducted following Cochrane and PRISMA guidelines. Eligible studies included randomized controlled trials and observational studies comparing at least two antithrombotic regimens in patients with non-valvular atrial fibrillation undergoing LAAO. Primary outcomes were major bleeding and thromboembolism. Secondary outcomes included device-related thrombosis (DRT) and all-cause mortality. Pairwise and network meta-analyses were performed using a random-effects model. Results A total of 52 studies involving 69751 patients were included. DOACs were consistently associated with significantly lower rates of major bleeding and all-cause mortality than other antithrombotic regimens. Low-dose DOACs showed a potential advantage over standard-dose DOACs in reducing major bleeding risk (RR 0.45, 95% CI: 0.22-0.92). Both standard- and low-dose DOACs reduced the risks of thromboembolism and DRT compared to antiplatelet therapy. In ranking analysis, DOACs emerged as the most effective and safest antithrombotic strategy, with low-dose DOACs demonstrating further safety benefits in bleeding outcomes (Figure 1). Conclusions DOACs provide a superior safety-efficacy profile compared to other antithrombotic strategies following LAAO, significantly reducing the risks of major bleeding, thromboembolic events, and mortality. While low-dose DOACs may offer additional bleeding risk reduction without compromising efficacy, further research is warranted to confirm their role in clinical practice.