Cardiology · Medical Literature
Long-term efficacy and safety of left atrial appendage closure vs. oral anticoagulation in atrial fibrillation: a meta-analysis of randomized controlled trials.
Abstract
Left atrial appendage closure (LAAC) has emerged as an alternative to oral anticoagulation (OAC) for stroke prevention in atrial fibrillation (AF), but its long-term comparative efficacy remains uncertain. This systematic review and meta-analysis evaluated randomized controlled trials (RCTs) comparing LAAC with OAC in AF. MEDLINE, Embase, Scopus, and the Cochrane Database of Systematic Reviews were searched through 8 April 2026. Risk ratios (RR) with 95% confidence intervals (CI) were pooled using random-effects models. Certainty of evidence (CoE) was assessed using GRADE. Six RCTs involving 7004 participants were included (3681 assigned to LAAC and 3323 to OAC). Compared with OAC, LAAC resulted in a significantly higher risk of ischaemic stroke or systemic embolism (134 vs. 80 events; RR 1.41, 95% CI 1.07-1.86; moderate CoE). No significant differences were observed for any stroke or systemic embolism (RR 1.10, 95% CI 0.87-1.39; moderate CoE), all-cause mortality (RR 0.92, 95% CI 0.77-1.10; high CoE), cardiovascular mortality (RR 0.90, 95% CI 0.67-1.21; moderate CoE), non-cardiovascular mortality (RR 0.92, 95% CI 0.75-1.12; moderate CoE), major bleeding (RR 0.91, 95% CI 0.77-1.08; high CoE), or haemorrhagic stroke (RR 0.58, 95% CI 0.28-1.17; moderate CoE). LAAC reduced the risk of nonprocedural clinically relevant bleeding compared with OAC (RR 0.50, 95% CI 0.43-0.59; high CoE). In patients with AF, LAAC results in a higher risk of ischaemic stroke or systemic embolism than an OAC-based strategy. Compared with OAC, LAAC has no effect on major bleeding or mortality and does not reduce haemorrhagic stroke.
Clinical relevance
This meta-analysis of 6 RCTs (n=7,004) directly addresses the long-standing clinical equipoise surrounding LAAC as an alternative to OAC for stroke prevention in AF — a question of high relevance given the growing procedural uptake of LAAC globally. It provides the most robust randomized evidence to date on long-term comparative efficacy and safety, using GRADE certainty-of-evidence ratings to guide clinical decision-making. Clinicians managing AF patients who are considered OAC-intolerant or who request LAAC must now reconcile these findings with current guideline recommendations.
Key findings
1. LAAC was associated with a significantly higher risk of ischaemic stroke or systemic embolism compared with OAC (134 vs. 80 events; RR 1.41, 95% CI 1.07–1.86; moderate certainty of evidence). 2. No significant difference was observed for the composite of any stroke or systemic embolism between LAAC and OAC (RR 1.10, 95% CI 0.87–1.39; moderate CoE). 3. All-cause mortality was not significantly different between groups (RR 0.92, 95% CI 0.77–1.10; high CoE), nor was cardiovascular mortality (RR 0.90, 95% CI 0.67–1.21; moderate CoE) or non-cardiovascular mortality (RR 0.92, 95% CI 0.75–1.12; moderate CoE). 4. Major bleeding rates were not significantly reduced with LAAC vs. OAC (RR 0.91, 95% CI 0.77–1.08; high CoE), and haemorrhagic stroke was not significantly different (RR 0.58, 95% CI 0.28–1.17; moderate CoE). 5. LAAC significantly reduced nonprocedural clinically relevant bleeding compared with OAC (RR 0.50, 95% CI 0.43–0.59; high CoE), representing the most robust safety signal in favour of LAAC. 6. The overall analysis included 6 RCTs with 3,681 patients allocated to LAAC and 3,323 to OAC, with evidence certainty assessed via GRADE methodology across all outcomes.
Practice implications
LAAC should not be routinely recommended as an efficacy-equivalent alternative to OAC for stroke prevention in AF, given the significantly higher risk of ischaemic stroke or systemic embolism (RR 1.41) with no offsetting reduction in major bleeding or mortality at high certainty of evidence. LAAC may retain a role in a narrowly selected population with AF who have absolute or near-absolute contraindications to any OAC and in whom nonprocedural bleeding risk is the dominant clinical concern, given the high-certainty 50% relative reduction in nonprocedural clinically relevant bleeding. Shared decision-making conversations with patients considering LAAC should explicitly convey the elevated ischaemic stroke risk relative to OAC, the absence of a major bleeding benefit, and the lack of mortality benefit, ensuring that patient expectations are aligned with the current evidence base.