“Left Atrial Appendage Closure Versus Medical Therapy in Atrial Fibrillation: A Systematic Review and Meta‐Analysis of Randomized Controlled Trials”
Key result
LAAC shows comparable outcomes to medical therapy for major events in AF despite underpowered evidence.
- n=7,004
Why the study?
The study aimed to compare the impact of left atrial appendage closure versus medical therapy on clinical outcomes in patients with AF, focusing on key outcomes relevant to thromboembolic prevention.
Does left atrial appendage closure improve clinical outcomes compared to medical therapy in adults with atrial fibrillation?
Key Points
- To compare the efficacy and safety of left atrial appendage closure versus medical therapy for thromboembolic prevention in patients with atrial fibrillation.
- Searched PubMed, Embase, Scopus, ClinicalTrials.gov, and Cochrane Library from inception to March 2026 following PRISMA guidelines.
- Included 6 randomized controlled trials encompassing 7,004 adult patients with atrial fibrillation.
- Pooled risk ratios with random-effects models, analyzed reconstructed Kaplan–Meier time-to-event data, and evaluated evidence conclusiveness with trial sequential analysis.
- Left atrial appendage closure showed comparable outcomes to medical therapy for all-cause mortality, any stroke, major bleeding, systemic embolism, and cardiac death, with similar cumulative incidence over time.
- There was a non-significant trend toward increased ischemic stroke and decreased hemorrhagic stroke with left atrial appendage closure.
- Trial sequential analysis showed the required information size was not met for any major endpoint, indicating current randomized evidence remains underpowered.
Study Design
Type
Meta-Analysis (n=7,004)
Structured PICO
Does left atrial appendage closure improve clinical outcomes compared to medical therapy in adults with atrial fibrillation?
P
Population
7,004 adults with atrial fibrillation from 6 randomized controlled trials comparing left atrial appendage closure with medical therapy.
I
Intervention
Left atrial appendage closure (LAAC)
C
Comparator
Medical therapy
O
Outcome
All-cause mortality, any stroke, ischemic stroke, hemorrhagic stroke, major bleeding, systemic embolism, and cardiac deathhard clinical
Limitations
- Current evidence remains underpowered as the required information size was not reached for any major endpoint
- Further adequately powered trials with longer follow-up are required
- Current evidence remains underpowered (required information size not reached for any major endpoint)
Key expert perspectives
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“While I am biased by being an author on this paper, I see the data as strengthening the case against using LAAC as a substitute for oral anticoagulation. There is a clear signal of higher rates of ischemic stroke. From a Bayesian point of view, the probability of reaching non-inferiority for stroke and systemic embolism using a lax measure of 1.4 is less than 50%.”
“These findings are quite disruptive and they go against a procedure - LAAC - which is largely performed. Analysing specifically all the various points of the trial, it is difficult to find out an explanation of these negative results, and this may give us a word of caution in performing large volume of LAAC, which is probably a procedure to be restricted to specific patients instead of being performed in any atrial fibrillation at high risk of ischemic and bleeding events.”
Implication
LAAC provides similar overall efficacy and safety compared with medical therapy for stroke prevention in AF, but current evidence is underpowered, supporting its continued reservation for selected patients.
Abstract
We aim to compare the impact of left atrial appendage closure vs. medical therapy on clinical outcomes in patients with atrial fibrillation, focusing on key clinical outcomes relevant to thromboembolic prevention. We conducted a PRISMA‐guided systematic review and meta‐analysis of studies comparing LAAC with medical therapy in AF adults. PubMed, Embase, Scopus, ClinicalTrial. gov, and Cochrane Library were searched from inception to March 2026. Outcomes included all‐cause mortality, any stroke, ischemic stroke, hemorrhagic stroke, major bleeding, systemic embolism and cardiac death. Risk ratios (RRs) with 95% confidence intervals (CIs) were pooled using random‐effects models. Reconstructed individual patient‐level survival data from published Kaplan–Meier curves were used for time‐to‐event analyses. Trial sequential analysis (TSA) assessed the conclusiveness of cumulative evidence. Six randomized controlled trials involving 7004 patients were included. LAAC demonstrated comparable outcomes to medical therapy for all‐cause mortality, any stroke, major bleeding, systemic embolism, and cardiac death. There was a non‐significant trend toward increased ischemic stroke and reduced hemorrhagic stroke with LAAC. Reconstructed time‐to‐event analyses showed similar cumulative incidence of stroke and bleeding outcomes over follow‐up. TSA demonstrated that the required information size was not reached for any major endpoint, indicating that current evidence remains underpowered and additional randomized trials are needed. LAAC provides similar overall efficacy and safety compared with medical therapy for stroke prevention in AF but should currently remain reserved for selected patients rather than replacing oral anticoagulation broadly. Further adequately powered trials with longer follow‐up are required.
Discussion
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Cite This Study
Al‐Janabi et al. (2026) conducted a meta-analysis in Atrial fibrillation (n=7,004). Left atrial appendage closure vs. Medical therapy was evaluated on All-cause mortality, any stroke, ischemic stroke, hemorrhagic stroke, major bleeding, systemic embolism and cardiac death. Left atrial appendage closure demonstrated comparable outcomes to medical therapy for mortality, stroke, and bleeding in atrial fibrillation, though evidence is underpowered.