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Whitlock RP, et al. "Left atrial appendage occlusion during cardiac surgery to prevent stroke". The New England Journal of Medicine. 2021. 384(22):2081-2091.
PubMedFull text

Clinical Question

In patients with atrial fibrillation undergoing cardiac surgery, does left atrial appendage occlusion reduce the risk of stroke compared to no procedure?

Bottom Line

Concomitant left atrial appendage occlusion at the time of cardiac surgery was found to reduce the risk of stroke compared to no left atrial appendage occlusion at the time of cardiac surgery.

Major Points

Atrial fibrillation places patients at risk of significant morbidity and mortality from stroke, with a key component of the care of patients with atrial fibrillation being stroke risk reduction. This is predominantly accomplished using anticoagulation to prevent thrombus formation. Studies in patients with non-rheumatic atrial fibrillation have found that the left atrial appendage accounts for approximately 90% of atrial thrombus location. [1] Therefore there has been interest in occlusion of the left atrial appendage to prevent thrombi formation and stroke.

The Left Atrial Appendage Occlusion Study (LAAOS III) was a blinded, randomized trial of surgical occlusion of the left atrial appendage at the time of another indicated cardiac surgery. The study found that left atrial appendage closure reduced the risk of ischemic stroke or systemic embolism by 2.2% absolute risk reduction during the almost four year follow-up period. There was no significant increase in operating time. Notably most patients remained on anticoagulation during the trial.

Overall, the findings support concomitant surgical left atrial appendage closure during another indicated cardiac surgery to reduce the incidence of ischemic stroke in patients with atrial fibrillation. Given that most patients remained on anticoagulation, the trial does not support left atrial appendage occlusion as an alternative to anticoagulation, unlike the design of the PROTECT AF trial of the WATCHMAN device compared to warfarin. Future studies could investigate outcomes with surgical left atrial appendage closure outside of another indicated cardiac surgery to see if the risk of surgery are outweighed by benefit in terms of ischemic stroke reduction.


As of June 2021, No guidelines have been published that reflect the results of this trial.


  • Multicenter, randomized, controlled trial
    • Participants, providers, and trial coordinators were blinded to treatment allocation
    • Surgeons were not blinded
  • N=4811
    • LAAOS (n=2400)
    • No LAAO surgery (n=2411)
  • Setting: 105 centers in 27 countries
  • Enrollment: July 2012 to October 2018
  • Mean follow-up: 3.8 years
  • Analysis: all participants that underwent cardiac surgery
  • Primary Outcome: first occurrence of ischemic stroke or non cerebral systemic embolism during follow-up.


Inclusion Criteria

  • Age 18 years or older
  • Planned for surgery with cardiopulmonary bypass
  • History of atrial fibrillation and CHA2DS2-VASc of at least 2

Exclusion Criteria

  • Mechanical-valve implantation
  • Heart transplantation
  • Surgery for complex congenital heart disease
  • Isolated implantation of LVAD
  • Prior surgery requiring opening the pericardium
  • Previous implantation of left atrial appendage closure device

Baseline Characteristics

  • Mean age: 71 years
  • Male sex: 68%
  • Median CHA2DS2-VASc score: 4
  • LVEF <50%: 31%


  • Randomized to undergo or not undergo left atrial appendage occlusion at the time of cardiac surgery.

    • preferred technique was amputation and closure, but several techniques were allowed.
  • stratified by trial site
  • surgeons performing procedure aware of trial assignment, but participants, clinicians, and other personnel were not.


Comparisons are LAAO vs No LAAO.

Primary Outcomes

Ischemic stroke or systemic embolism
4.8% vs 7.9% (HR 0.67; 95% CI 0.53-0.85; P=0.001)

Secondary Outcomes

Ischemic stroke
4.6% vs 6.9% (HR 0.66; 95% CI 0.52-0.84)
Systemic embolism
0.3 vs 0.3% (HR 0.86; 95% CI 0.29-2.55)
Any stroke
4.7% vs 7.4% (HR 0.63; 95% CI 0.50-0.80)
Death from any cause
22.6% vs 22.5% (HR 1.00; 95% CI 0.89-1.13)

Subgroup Analysis

There was no significant treatment heterogeneity by important subgroups such as age, sex, surgery type, or prior atrial fibrillation ablation.

Adverse Events

Major bleeding event
10.4% vs 11.2% (HR 0.93; 95% CI 0.78-1.11)
Bypass time (min)
119 +/- 48 vs 113 +/- 47 (difference 5; 95% CI 3-8)
Cross-clamp time (min)
86 +/- 37 vs 82 +/- 37 (difference 4; 95% CI 1-6)



Canadian Institutes of Health Research Canadian Stroke Prevention Intervention Network Hamilton Health Sciences Research Institute Heart and Stroke Foundation of Canada Request for Applications Program-Research Strategic Initiatives Canadian Network and Centre for Trials Internationally McMaster University Surgical Associates

Further Reading

  1. Blackshear, Joseph L., and John A. Odell. "Appendage obliteration to reduce stroke in cardiac surgical patients with atrial fibrillation." The Annals of thoracic surgery 61.2 (1996): 755-759.