ABSTRACT
Occluding the left atrial appendage during cardiac surgery for other indications reduced the risk of ischemic stroke or systemic embolism in patients with atrial fibrillation in LAAOS III (the third Left Atrial Appendage Occlusion Study) (N Engl J Med 2021; 384(22):2081–2091). But questions remain.
Left atrial appendage occlusion during cardiac surgery showed a 32% relative risk reduction in ischemic stroke or systemic embolism, a significant benefit for patients with atrial fibrillation and elevated stroke risk.
The benefit appears additive to that of standard anticoagulation, suggesting that this procedure may provide an additional layer of protection in patients at high risk.
No significant increase in perioperative complications (eg, bleeding or infection) was observed in the occlusion group, reinforcing that this procedure can be performed safely when bundled with routine cardiac surgery.
The results position surgical left atrial appendage occlusion as a potential standard of care for eligible patients undergoing cardiac surgery, particularly those at high risk of stroke.
Whenever patients who have atrial fibrillation undergo cardiac surgery, including coronary artery bypass grafting or surgical repair or replacement of heart valves, the patient’s risk of thromboembolic stroke can be lowered if the surgeon seizes the opportunity to also occlude the left atrial appendage.
This was the principal finding of LAAOS III (the third Left Atrial Appendage Occlusion Study).1 But questions remain about who should undergo this procedure, whether patients who undergo the procecure need to keep taking oral anticoagulants, and which surgical technique is best. Below, we summarize the LAAOS III trial’s rationale, methods, and results and discuss its controversies.
OCCLUDE THE APPENDAGE, PREVENT A STROKE?
Patients with atrial fibrillation have a significantly higher risk of stroke, often caused by embolization of clots that form in the left atrial appendage.2 In fact, atrial fibrillation is responsible for roughly a quarter of ischemic strokes,3,4 many of which are cardioembolic.5
Multiple studies have examined whether occluding the left atrial appendage, either percutaneously or surgically, can reduce the risk of stroke in patients with atrial fibrillation, especially those at high risk of bleeding who therefore cannot tolerate long-term anticoagulation.
PROTECT AF (Watchman Left Atrial Appendage System for Embolic Protection in Patients With Atrial Fibrillation)6 compared left atrial appendage occlusion using the percutaneously inserted Watchman device, after which warfarin was discontinued, vs ongoing warfarin therapy in patients with nonvalvular atrial fibrillation. The device was not inferior to warfarin for preventing stroke, systemic embolism, and cardiovascular death, though the rate of adverse events was higher in the procedure group, mainly due to periprocedural complications (pericardial effusion, procedure-related thrombotic stroke, device embolization).
PREVAIL (Prospective Randomized Evaluation of the Watchman Left Atrial Appendage Closure Device in Patients With Atrial Fibrillation Versus Long-Term Warfarin Therapy)7 was conducted to address safety concerns from PROTECT AF. It confirmed that the Watchman device had comparable efficacy to warfarin, and the procedural safety had improved since the earlier trial.
LAAOS I8 showed that surgical left atrial appendage occlusion could be safely performed with a low risk of complications, but it did not specifically assess whether the procedure lowered the risk of stroke in the long term.
LAAOS II9 showed that surgical left atrial appendage occlusion was achievable in most patients and was safe. However, the trial lacked power to assess the efficacy of surgical left atrial appendage closure in reducing strokes.
Thus, although these earlier studies showed that surgical left atrial appendage occlusion was feasible and had potential, large randomized trials were needed to establish definitive evidence for its role in stroke prevention.
Managing atrial fibrillation in patients who undergo cardiac surgery presents a clinical dilemma, as long-term anticoagulation remains the standard for stroke prevention but carries significant bleeding risks. Also, many patients do not adhere to it. While surgical left atrial appendage occlusion offers a potential adjunct or alternative to anticoagulation, its routine integration into surgical practice remains controversial due to uncertainties regarding efficacy, durability, and the need for continued anticoagulation.
The LAAOS III trial aimed to address these important questions and provide evidence to guide clinical decision-making, specifically to provide robust evidence on whether left atrial appendage occlusion during surgery improves stroke outcomes in patients with atrial fibrillation.
LAAOS III: A LARGE RANDOMIZED TRIAL
LAAOS III,1 published in 2021, was a multicenter randomized controlled trial that enrolled 4,811 patients, all of whom had atrial fibrillation at baseline and a CHA2DS2-VASc score of at least 2 (1 point given for congestive heart failure; hypertension; age 65 to 74 years or ≥ 75 years [doubled]; diabetes mellitus; prior stroke, transient ischemic attack, or thromboembolism [doubled]; vascular disease; female sex; possible scores range from 0 to 9, and the higher the score the higher the risk of stroke), who were undergoing cardiac surgery for another indication.
Participants were randomized in a 1:1 ratio to undergo either surgical left atrial appendage occlusion in addition to their planned cardiac surgery, or cardiac surgery without left atrial appendage occlusion. Although the surgeons knew which group the patients were in, the patients themselves, their other caregivers, and the researchers were blinded to the treatment. The median follow-up was 3.8 years.
The primary outcome was a composite of ischemic stroke or systemic embolism. Secondary outcomes included individual components of the primary outcome as well as safety outcomes such as bleeding and all-cause mortality.
MODEST BUT MEANINGFUL BENEFIT
Left atrial appendage occlusion reduced the risk of ischemic stroke or systemic embolism: the incidence was 4.8% in the occlusion group vs 7.0% in the control group over the follow-up period.1 This corresponds to a 32% relative risk reduction (hazard ratio 0.67, 95% confidence interval 0.53–0.85, P = .001).
The absolute risk reduction was therefore 2.2% over a mean follow-up of 3.8 years. We calculate the number needed to treat as 45 patients to prevent 1 ischemic stroke or systemic embolism over this period. These figures represent a modest absolute benefit but a meaningful impact in a population at elevated risk for stroke.
Compared with controls, the rate of perioperative complications such as bleeding or infection was not significantly higher in the occlusion group. The benefit of the procedure was consistent across subgroups, regardless of anticoagulation use after surgery. The mortality rate did not differ significantly between the groups. However, at 1 year, less than 80% of patients in both treatment groups remained on oral anticoagulation, indicating that more than 20% of patients in the control group were left without stroke prevention.
HOW WILL THIS CHANGE PRACTICE?
The LAAOS III trial1 provided compelling evidence that has the potential to change clinical practice in managing patients with atrial fibrillation undergoing cardiac surgery in several ways:
The trial supports integrating left atrial appendage occlusion as a standard practice during cardiac surgery for patients with atrial fibrillation, especially those at high risk of stroke.
Current guidelines on managing atrial fibrillation and preventing stroke may be updated to recommend surgical left atrial appendage occlusion for patients undergoing cardiac surgery.
While device-based left atrial appendage closure is typically reserved for patients with contraindications to anticoagulation, surgical occlusion during cardiac surgery may now be considered for a broader population, even those receiving anticoagulation.
Cardiologists and cardiac surgeons may work more closely to identify candidates for surgical left atrial appendage occlusion, ensuring it is incorporated into preoperative planning.
The study highlights the need for training and standardization of surgical techniques to ensure effective and complete left atrial appendage closure, which is critical for reducing residual stroke risk.
CONTROVERSIES AND UNANSWERED QUESTIONS
Although it is a benchmark for future atrial fibrillation guidelines, the LAAOS III trial leaves some questions to be answered.
Can occlusion replace anticoagulation?
At baseline, only a little more than half of the patients in LAAOS III were on anticoagulation, but at discharge from the hospital, this had increased to 83.4% of the occlusion group and 81.0% of the control group.1 At 3 years, the numbers were 75.3% vs 78.2%. Could left atrial appendage occlusion allow some patients to stop anticoagulation safely, reducing bleeding risks? This critical question was not directly addressed, but, as reviewed by Soltesz and Gillinov,10 several randomized controlled clinical trials and a meta-analysis showed this procedure to be an acceptable alternative to oral anticoagulation in patients with atrial fibrillation at increased stroke risk.
LAAOS III did not specifically evaluate patients unable or unwilling to take anticoagulants.1 How well does surgical left atrial appendage occlusion perform in this population compared with newer stand-alone devices like Watchman? Which strategy offers better long-term outcomes, and how should the 2 approaches be sequenced or prioritized?
Which type of oral anticoagulant is best?
A 2023 subanalysis of the LAAOS III data by Connolly et al11 examined the interaction between oral anticoagulation adherence and left atrial appendage occlusion outcomes. It found that, while surgical occlusion provided benefits overall, its effect appeared less pronounced in patients receiving direct oral anticoagulants than in patients on vitamin K antagonists. Given that direct oral anticoagulants are now the standard of care, would the results of LAAOS III have differed if all patients had received them?
Because the trial did not mandate specific anticoagulation regimens, future studies should explore whether the benefit of surgical left atrial appendage occlusion remains consistent with different oral anticoagulants, particularly direct oral anticoagulants. This would provide crucial insight into the optimal stroke prevention strategy for patients with atrial fibrillation undergoing cardiac surgery.
Which patients should undergo occlusion?
The LAAOS III trial demonstrated a 32% relative risk reduction in ischemic stroke or systemic embolism, but the absolute risk reduction was modest at 2.2% over a median follow-up of 3.8 years.1 This raises the question of whether surgical left atrial appendage occlusion should be widely adopted, particularly in patients at lower risk. For individuals with lower CHA2DS2-VASc scores or well-controlled anticoagulation use, the incremental benefit of this procedure may not outweigh the procedural risks or added surgical complexity. Conversely, even a modest absolute risk reduction may translate into meaningful clinical benefits in patients at higher risk.
Therefore, while LAAOS III supports left atrial appendage occlusion as a valuable adjunct in patients at high risk of stroke undergoing cardiac surgery, its role in those at lower risk remains uncertain and requires further investigation.
Which occlusion technique is best?
A key limitation of the LAAOS III trial1 was that it did not mandate a specific occlusion technique, leading to variability in surgical approaches (internal ligation, stapled excision, clipping with an external device such as the AtriClip, or amputation and oversewing). This raises concerns regarding incomplete left atrial appendage closure, which has been associated with an increased risk of thrombus formation. Studies suggest that a partially closed left atrial appendage may be more thrombogenic than an untouched appendage due to altered flow dynamics and residual communication with the left atrium.12
Obtain transesophageal echocardiography afterward?
The LAAOS III trial did not mandate any postoperative imaging, such as transesophageal echocardiography, to confirm the completeness of left atrial appendage occlusion. This is in contrast to the trials of percutaneous occlusion devices, such as PROTECT AF6 and PREVAIL,7 which required routine transesophageal echocardiographic follow-up (typically at 45 days) to verify device positioning and closure.
The lack of imaging raises the possibility that some surgical left atrial appendage occlusion procedures resulted in incomplete occlusion, which may contribute to residual stroke risk. This highlights the need for better intraoperative and postoperative assessment of surgical left atrial appendage occlusion efficacy, as well as research into whether certain techniques—such as stapling, excision, or clipping—offer superior long-term stroke prevention with minimal residual risk.
Occlusion for all?
An analysis from the Nationwide Readmissions Database13 concluded that placing a clip on the left atrial appendage was associated with a lower early postdischarge incidence of stroke and a favorable overall risk-benefit profile in all patients undergoing cardiac surgery, not just those with atrial fibrillation.
In addition, a 2024 meta-analysis concluded that concomitant left atrial appendage occlusion was associated with reduced stroke rates at early and long-term follow-up and possibly reduced all-cause mortality at long-term follow-up.14 However, the benefits were limited to patients with preoperative atrial fibrillation. There was insufficient evidence to support routine concomitant left atrial appendage occlusion in patients without atrial fibrillation. For those reasons, long-term follow-up data are needed to confirm sustained benefits, particularly as patients’ stroke risk evolves-over time.
Is surgical occlusion cost-effective?
Although adding left atrial appendage occlusion to cardiac surgery is relatively low-cost,15 its cost-effectiveness remains an important consideration, particularly in healthcare systems with limited resources. Because left atrial appendage occlusion is often performed concomitantly with cardiac surgery (in the United States, it was performed in more than 85% of concomitant surgical ablation procedures),16 it adds minimal additional procedural costs compared with stand-alone percutaneous left atrial appendage closure, which requires specialized devices and follow-up imaging.
However, the long-term economic benefits of surgical left atrial appendage occlusion depend on whether it reduces stroke-related healthcare costs and the need for prolonged anticoagulation. In high-income settings, cost-effectiveness analyses have generally favored percutaneous left atrial appendage occlusion in patients with contraindications to anticoagulation. In contrast, in resource-limited settings, surgical occlusion may offer a more accessible stroke prevention strategy if the procedural success rate is high and patients are selected appropriately. Future studies should assess whether the modest absolute risk reduction observed in LAAOS III translates into meaningful healthcare cost savings across different economic environments.
What is the role for surgical ablation of atrial fibrillation?
In LAAOS III, 34% of the occlusion group and 31.5% of the control group underwent concomitant surgical ablation of atrial fibrillation.1 Catheter-based and surgical ablation of atrial fibrillation continue to evolve,17 and if ablation can correct the heart rhythm and suppress the atrial fibrillation, we would expect it to reduce the risk of stroke.
FUTURE RESEARCH DIRECTIONS
Future trials are warranted and should focus on the following:
Comparing surgical left atrial appendage occlusion with stand-alone percutaneous devices in specific populations such as patients who cannot tolerate anticoagulation
Whether left atrial appendage occlusion alone suffices to protect against stroke in patients unable to tolerate anticoagulation
Which surgical technique is optimal to ensure consistent closure and eliminate residual thrombotic risks
Actively identifying patient subgroups that benefit most (or least) from left atrial appendage occlusion, refining criteria for its use.
AN ADJUNCTIVE STRATEGY IN APPROPRIATE CASES
The LAAOS III trial1 demonstrated that adding left atrial appendage occlusion to routine cardiac surgery significantly reduces the risk of ischemic stroke or systemic embolism in patients with atrial fibrillation and high stroke risk, without increasing surgical complications. These findings support incorporating this procedure into the standard surgical care for eligible patients with atrial fibrillation undergoing cardiac surgery. This trial has influenced guidelines on stroke prevention in patients with atrial fibrillation, emphasizing the role of surgical left atrial appendage occlusion as an adjunctive strategy in appropriate cases.
However, the trial has not established left atrial appendage occlusion as a definitive alternative to anticoagulation yet. Current expert recommendations suggest that occlusion should be viewed as an adjunct rather than a replacement for oral anticoagulation, except in cases where anticoagulation is contraindicated. Questions remain about its role in anticoagulation management, its performance in nonsurgical settings, and its cost-effectiveness compared with alternatives.
Future studies should focus on whether left atrial appendage occlusion alone is sufficient for stroke prevention in select patients at high risk of bleeding and will thus help resolve these ambiguities, ensuring the intervention is used optimally.
DISCLOSURES
Dr. Soltesz has disclosed teaching and speaking for Abbott Vascular, Abiomed, and Atricure. Dr. Djordjević reports no relevant financial relationships which, in the context of their contributions, could be perceived as a potential conflict of interest.
Acknowledgments:
The authors acknowledge the editorial services of Urška Antonic of University Medical Centre Maribor, Maribor, Slovenia.
- Copyright © 2025 The Cleveland Clinic Foundation. All Rights Reserved.
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