October 1, 2026Stroke
Updated Meta-Analysis of Left Atrial Appendage Closure Versus Oral Anticoagulation to Prevent Stroke in Atrial Fibrillation
PRINCE KWABLA PEKYI-BOATENGArankesh MahadevanSmith Kofi FrimpongLilly KanishkaStephen GbekorHamilton AbimbillaBrian Jose Villafuerte-TrisoliniGeorge BlanksonP. Pekyi-BoatengDan Youg NguyenOmid ShorakaJana WoldAaron ShoskesStephanie LydenPugazhendhi VijayaramanJaydevsinh DoliaJennifer J. MajersikAnwar TandarKarol P. BudohoskiRamesh Grandhi
Key result
LAAC shows no benefit over oral anticoagulation for overall stroke, with higher ischemic stroke risk.
- OR 1.10
- 95% CI 0.78-1.56
- n=7,028
Why the study?
Randomized evidence comparing percutaneous left atrial appendage closure with oral anticoagulation in nonvalvular atrial fibrillation was limited before two large 2026 trials.
Does percutaneous left atrial appendage closure reduce stroke, bleeding, and mortality compared to oral anticoagulation in patients with nonvalvular atrial fibrillation?
Key Points
- To evaluate the pooled effects of percutaneous left atrial appendage closure compared with oral anticoagulation on stroke, bleeding, and mortality across different bleeding risk profiles and anticoagulant regimens.
- Systematic review and meta-analysis searching PubMed, Scopus, and Embase through April 15, 2026, for randomized controlled trials comparing percutaneous left atrial appendage closure to oral anticoagulation in nonvalvular atrial fibrillation (PROSPERO CRD420261370546).
- Analyzed six randomized controlled trials across 358 multicenter sites in North America, Europe, and Asia encompassing 7,028 patients.
- Calculated pooled odds ratios (OR) for cumulative-incidence clinical outcomes using random-effects models, Cochrane Risk of Bias 2 evaluations, and trial sequential analysis.
- Overall stroke rates showed no statistically significant difference between closure and anticoagulation arms (OR, 1.10 [95% CI, 0.78–1.56]).
- Ischemic stroke occurred significantly more often with left atrial appendage closure (OR, 1.41 [95% CI, 1.07–1.86]), though this outcome did not reach the optimal information size in trial sequential analysis.
- Nonprocedural bleeding was significantly reduced with left atrial appendage closure (OR, 0.58 [95% CI, 0.35–0.96]), which met the required information size and was observed in standard-risk and postablation cohorts but not in high-bleeding-risk cohorts.
Study Design
Type
Meta-Analysis (n=7,028)
Multicenter
Yes
Structured PICO
Does percutaneous left atrial appendage closure reduce stroke, bleeding, and mortality compared to oral anticoagulation in patients with nonvalvular atrial fibrillation?
P
Population
7,028 patients with nonvalvular atrial fibrillation across 6 randomized controlled trials comparing left atrial appendage closure with oral anticoagulation.
I
Intervention
Percutaneous left atrial appendage closure (LAAC)
C
Comparator
Oral anticoagulation (warfarin in 2 trials, direct oral anticoagulant in 4 trials)
O
Outcome
Stroke, bleeding, and mortalityhard clinical
Main Result
Odds Ratio: 1.1 (95% CI 0.78–1.56)
LAAC reduces nonprocedural bleeding compared to oral anticoagulation in standard-to-moderate bleeding risk patients, but is associated with a higher risk of ischemic stroke.
Limitations
- Ischemic stroke outcome did not reach the required information size
Ask about this paper
Answers are grounded in this paper and cite their sources.
Key expert perspectives
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“Although the rates of stroke and major bleeding appear to be similar between the groups, our analysis also highlighted a significant 27% reduction in non-procedural major bleeding rates in patients undergoing LAAC and a 34% increase in ischaemic stroke”
“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%.”
“The trial has been well executed from the methodological point of view. Its 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
Stroke rates similar with LAAC versus warfarin; extends RCT data by pooling evidence in AF.
Abstract
BACKGROUND: Ninety percent of left atrial thrombi in nonvalvular atrial fibrillation arise in the left atrial appendage, which can be occluded percutaneously (left atrial appendage closure [LAAC]). Two 2026 trials (CHAMPION-AF and CLOSURE-AF) more than doubled the available randomized evidence comparing LAAC with oral anticoagulation. We evaluated pooled effects of LAAC on stroke, bleeding, and mortality by bleeding risk, anticoagulation eligibility, and comparator. METHODS: In this systematic review and meta-analysis, we searched PubMed, Scopus, and Embase from inception to April 15, 2026, for randomized controlled trials comparing percutaneous LAAC with oral anticoagulation in nonvalvular atrial fibrillation. Risk of bias was assessed with the Cochrane Risk of Bias 2 tool. Cumulative-incidence outcomes were pooled as odds ratios using random-effects models, with prediction intervals, prespecified subgroups, and trial sequential analysis. RESULTS: Six randomized controlled trials (2014-2026; 358 sites in North America, Europe, and Asia; 7028 patients) compared LAAC with warfarin (2 trials) or a direct oral anticoagulant (4 trials); populations were predominantly anticoagulation-eligible with low prior-stroke prevalence, plus 2 high-bleeding-risk and 1 postablation trial. Overall stroke rates were similar between arms (odds ratio, 1.10 [95% CI, 0.78-1.56]). Ischemic stroke was more frequent with LAAC (odds ratio, 1.41 [95% CI, 1.07-1.86]) but did not reach the required information size. Nonprocedural bleeding was lower with LAAC (odds ratio, 0.58 [95% CI, 0.35-0.96]), the only outcome reaching a sufficient information size, in standard-risk and postablation but not high-bleeding-risk patients. CONCLUSIONS: LAAC is best positioned to reduce nonprocedural bleeding in anticoagulation-eligible patients at standard-to-moderate bleeding risk, rather than as a stroke-equivalent substitute for oral anticoagulation. REGISTRATION: URL: https://www.crd.york.ac.uk/PROSPERO/; Unique identifier: CRD420261370546.
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Cite This Study
PEKYI-BOATENG et al. (2026) conducted a meta-analysis in Nonvalvular atrial fibrillation (n=7,028). Left atrial appendage closure vs. Oral anticoagulation was evaluated on Overall stroke (OR 1.10, 95% CI 0.78-1.56). Left atrial appendage closure resulted in similar overall stroke rates compared to oral anticoagulation, but increased ischemic stroke and reduced nonprocedural bleeding.