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

## TL;DR

This study compares anticoagulant strategies after heart device implantation and finds that low-dose DOACs reduce bleeding and mortality risks effectively.

## Contribution

A network meta-analysis identifies low-dose DOACs as a safer and more effective antithrombotic strategy following left atrial appendage occlusion.

## Key findings

- DOACs significantly reduce major bleeding and mortality compared to other antithrombotic regimens.
- Low-dose DOACs further reduce bleeding risk without compromising efficacy.
- Standard-dose DOACs outperform SAPT and DAPT in preventing thromboembolism and device-related thrombosis.

## Abstract

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 favourable safety–efficacy profile, with low-dose regimens showing potential benefits during the device endothelialization period. This network meta-analysis (NMA) aimed to compare the efficacy and safety of various antithrombotic strategies, including DOAC dosing, following LAAO.

A systematic review and NMA were conducted following Cochrane and PRISMA guidelines. Eligible studies included randomized controlled trials (RCT) and observational studies comparing at least two antithrombotic regimens in patients with non-valvular atrial fibrillation undergoing percutaneous 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. A total of 52 studies (49 observational and 3 RCTs) involving 69 751 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 (odds ratio 0.45, 95% confidence interval: 0.22–0.92). For thromboembolism and DRT, standard-dose DOAC significantly reduced risk compared with single antiplatelet therapy (SAPT) but not with dual antiplatelet therapy (DAPT), whereas low-dose DOAC significantly reduced both outcomes compared with SAPT, DAPT, and vitamin K antagonists plus SAPT. In ranking analysis, DOACs emerged as the most effective and safest antithrombotic strategy, with low-dose DOACs demonstrating further safety benefits in bleeding outcomes.

DOACs provide a superior safety–efficacy profile compared with 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.

Graphical Abstract