LAAOS III
(2021)Objective
To determine whether concomitant left atrial appendage occlusion during cardiac surgery reduces ischemic stroke or systemic embolism in patients with atrial fibrillation receiving usual care including anticoagulation
Study Summary
• Benefit was more pronounced after 30 days post-surgery (HR 0.58) than within first 30 days (HR 0.82)
• No increase in perioperative bleeding, heart failure, or mortality with the procedure
Intervention
Surgical left atrial appendage occlusion (amputation and closure, stapler closure, double-layer linear closure, or approved surgical device) during cardiac surgery for another indication
Inclusion Criteria
Age ≥18 years, scheduled cardiac surgery with cardiopulmonary bypass, history of atrial fibrillation, CHA2DS2-VASc score ≥2
Study Design
Arms: 1) LAA occlusion during cardiac surgery with usual care; 2) No LAA occlusion during cardiac surgery with usual care
Patients per Arm: Occlusion: 2379; No occlusion: 2391
Outcome
• NNT of 37 over 5 years to prevent one stroke
• No significant difference in mortality (22.6% vs 22.5%), major bleeding, or heart failure hospitalization
Bottom Line
Among patients with atrial fibrillation undergoing cardiac surgery, concomitant left atrial appendage occlusion reduced the risk of stroke or systemic embolism by 33% compared to no occlusion, with a number needed to treat of 37 over 5 years. The procedure did not increase perioperative bleeding, heart failure, or mortality. The benefit was additive to ongoing anticoagulation therapy.
Major Points
- Left atrial appendage occlusion reduced ischemic stroke/systemic embolism from 7.0% to 4.8% (HR 0.67, 95% CI 0.53-0.85, P=0.001)
- The treatment effect was more pronounced beyond 30 days (HR 0.58) than within the first 30 days post-surgery (HR 0.82)
- 76.8% of participants continued oral anticoagulation at 3 years, indicating the benefit was additive to anticoagulation
- 92.1% of participants received the assigned procedure with high compliance
- No significant increase in heart failure hospitalization despite theoretical concerns about atrial natriuretic peptide
- The NNT was 37 (95% CI 22-111) over 5 years to prevent one stroke
- Multiple occlusion techniques were used successfully including cut-and-sew (55.7%), closure device (15.1%), stapler (11.2%), and closure from within (13.8%)
- The trial was stopped early by the data safety monitoring board after the second interim analysis showed clear benefit
Study Design
- Study Type
- Multicenter randomized controlled trial
- Randomization
- Yes
- Blinding
- Participants, trial personnel, and clinicians (other than surgeons) were blinded to trial-group assignments. Surgeons received confidential email with assignment just before surgery. Surgical reports indicated only enrollment in LAAOS III without specifying group assignment.
- Sample Size
- 4770
- Follow-up
- Mean 3.8 years (final follow-up January-March 2021)
- Centers
- 105
- Countries
- Canada, Italy, Germany, Czech Republic, Greece, Russia, USA, Australia, New Zealand, Netherlands, UK, Brazil, and 15 others
Primary Outcome
Definition: First occurrence of ischemic stroke (including transient ischemic attack with positive neuroimaging) or non-cerebral systemic embolism. Strokes of undetermined cause were included as ischemic strokes.
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| 168/2391 (7.0%) | 114/2379 (4.8%) | 0.67 (0.53 to 0.85) | 0.001 |
Limitations & Criticisms
- Lack of direct comparison between LAA occlusion and oral anticoagulation - cannot determine if occlusion could replace anticoagulation
- Findings apply primarily to surgical occlusion performed as a concomitant procedure during cardiac surgery, not to stand-alone surgical or endovascular occlusion
- Cannot discern whether all surgical closure methods are comparable in efficacy
- Did not examine whether occlusion was sustained over follow-up (no imaging confirmation of persistent closure)
- The trial was stopped early which may affect precision of effect estimates
- High perioperative stroke rate (2.2-2.7% in first 30 days) reflects surgical population and may dilute early treatment effect
- Information on occlusion method was only collected for 70.8% of patients in the occlusion group
Citation
N Engl J Med 2021;384:2081-91