OPTION

Published

Wazni OM, et al. "Left atrial appendage closure after ablation for atrial fibrillation". The New England Journal of Medicine. 2025. 392(13):1277-1287.
PubMed • Full text • PDF • ClinicalTrials.gov

Clinical Question

Among adults with non-valvular AF with elevated CHA2DS2-VASc scores, is AF ablation followed by LAA occlusion non-inferior for embolic events and superior for bleeding events when compared to AF ablation followed by anticoagulation?

Bottom Line

Among adults with non-valvular AF with elevated CHA2DS2-VASc scores, AF ablation followed by LAA occlusion is non-inferior for embolic events and superior for bleeding events when compared to AF ablation followed by anticoagulation.

Major Points

Systemic embolism, including stroke, is a major complication from atrial fibrillation and guidelines recommend interventions like oral anticoagulation therapy to lower risk of systemic embolism among persons with AF at higher risk for such an event (2023 ACC/AHA guidelines: COR 1, LE A). Among persons with non-valvular AF, 90% of atrial thrombi originate in the left atrial appendage (LAA). It has been hypothesized that persons with AF who undergo ligation or occlusion of the LAA may not require anticoagulation therapy. To this point, surgical ligation of the LAA was associated with fewer strokes among patients undergoing cardiac surgery with AF and higher stroke risk in the 2021 LAAOS III trial. The WATCHMAN device is a percutaneously-placed device that occludes the LAA. The 2009 PROTECT AF trial found the first generation WATCHMAN to be non-inferior to warfarin for a composite outcome of ischemic or hemorrhagic stroke, systemic embolism, cardiovascular mortality, or unexplained mortality. The device was not found to be non-inferior to warfarin for reduction in ischemic strokes, of note. Because of weaker evidence, there is not a strong recommendation for use of LAA occlusion devices among persons with AF, and guidelines suggest its use in persons who may not tolerate long-term anticoagulation therapy.

Contemporary AF practice has changed with emergence of DOACs. Additionally, the WATCHMAN device has undergone generational changes and may now have fewer adverse events. Further, rhythm control strategies (including AF ablation) may provide additional stroke risk reduction when compared to rate control, as was shown in the 2020 EAST-AFNET 4 trial. Whether the current generation WATCHMAN device combined with AF ablation is associated with non-inferiority for systemic embolism or mortality events and superiority in terms of bleeding events when compared to anticoagulation was unknown.

Published in 2025, the cOmParison of anTIcoagulation with left atrial appendage clOsure after atrial fibrillation ablatioN (OPTION) trial randomized 1,600 participants with non-valvular AF and elevated CHA2DS2-VASc score who are eligible for anticoagulation to (1) AF ablation followed by LAA closure or (2) AF ablation followed by anticoagulation. The trial excluded persons with valvular AF and those with LVEF ≤30 or NYHA class IV HF symptoms. At 36 months, the LAA closure was found to be non-inferior to anticoagulation for the efficacy outcome, which included all-cause mortality, stroke, or systemic embolism (5.3% vs. 5.8%; non-inferiority P<0.001), and superior to anticoagulation for the safety outcome, which included non-procedure related major bleeding or clinically relevant nonmajor bleeding (3.9% vs. 5.0%; HR 0.44; 95% CI 0.33 to 0.59; P<0.001). Of note, there were similar numbers of ischemic strokes, hemorrhagic strokes, and systemic embolism events in both arms.

OPTION provides initial evidence that a strategy of AF ablation followed by LAA occlusion may be an ideal strategy to lower risk of stroke or systemic embolism among adults with non-valvular AF who have an elevated CHA2DS2-VASc score.

Guidelines

As of April 2025, no guidelines have been published that reflect the results of this trial.

Design

• Multicenter, open-label, randomized controlled trial
• N=1600
  • LAA closure (n=803)
  • Anticoagulation (n=797)
• Setting: 106 sites in 10 countries in the US, Europe, & Australia
• Enrollment: 2019-2021
• Follow-up: 36 months
• Analysis: Intention-to-treat
• Primary efficacy outcome: All-cause mortality, stroke, or systemic embolism (non-inferiority)
• Primary safety outcome: Non-procedure related major bleeding or clinically relevant nonmajor bleeding (superiority)

Population

Inclusion Criteria

• Legal age to participate per country
• Non-valvular AF with catheter ablation in prior 90-180 days or planned to have clinically-indicated ablation in following 10 days
• CHA2DS2-VASc score ≥2 if male or ≥3 if female
• Reasonable that the participant would be assigned to pharmacological regimen based upon their clinical status
• Able to undergo TEE
• Written/informed consent and able/willing to return for follow-up visits

Exclusion Criteria

• TTE with any of the following:
  • LVEF <30%
  • Pericardial effusion with echo-free space >5 mm
  • High-risk PFO with any of the following:
    • Atrial septal aneurysm excursion >15 mm or length >15 mm
    • Large shunt (early/within 3 beats and/or substantial bubble passage)
  • Significant MV stenosis (MV area <1.5 cm²
• In another trial that would interfere with the current study
• Require long-term anticoagulation for non-AF reasons or unsuitable for use of long-term anticoagulation or antiplatelet therapy
• Planned cardiac or major surgery in 30 days before and 60 days after randomization
• TIA in 60 days before randomization
• ISTH major bleed in 14 days before randomization
• MI in 90 days before randomization
• Prior AD/PFO repair
• Prosthetic valve
• Usual pregnancy/childbearing exclusions
• Life expectancy <2 years
• Cardiac tumor, acute/chronic pericariditis, tamponade physiology, or active infection
• Contraindication to catheterizations
• NYHA class IV HF symptoms
• Prior LAA closure

Baseline Characteristics

From the LAA closure group except where classified.

• Demographics: Age 70 years, 65% males, White race 84%, Black race 2%, Hispanic/Latino 2%, Asian 0.5%, AIAN 0.2%, other 0.4%, not disclosed 12%
• CHA2DS2-VASc: 3.5; one 0.6%, two-three 53%, four-five 39%, six+ 8%
• HAS-BLED: 1.2; zero 18%, one-two 75%, three+ 3%
• AF type: Persistent 41%, paroxysmal 59%, present for <1y 32%, present for ≥1y 68%
• Ablation timing:
  • (LAA closure arm) 90-180 days before randomization: 59%
  • (Anticoagulation arm) 90-18 days before randomization: 59%
  • (LAA closure arm) Concomitant with LAA closure, within 10 days after randomization: 41%
  • (Anticoagulation arm) Within 10 days of after randomization: 41%

Interventions

• Participants were randomized to a group:
  • LAA closure - with WATCHMAN FLX device, if ablation was performed in the same procedure, the WATCHMAN device was placed after the ablation. Patients received anticoagulation+aspirin for 90 days then aspirin alone through 12 months.
    • Participants were allowed to undergo ablations at the time of the WATCHMAN implant procedure, excluding LAA catheter ablation, non-standard ablation, non-AF-related ablation (e.g., Vtach but CTI and cardioversion allowed), other procedures such as PPM/ICD procedures or TAVR-like procedures.
    • TEE or CT scan assesment of the device was performed at 3 and 12 months.
  • Anticoagulation - Start or continuation of anticoagulation, with selection at the treating physician's discretion.

Outcomes

Presented as LAA closure vs. anticoagualtion except where noted.

Primary Outcomes

Primary efficacy outcome

All-cause mortality, stroke, or systemic embolism

Non-inferiority with 5% margin

5.3% vs. 5.8% (difference -0.5; 97.5% one-sided upper confidence limit 1.8; HR 0.91; 95% CI 0.59 to 1.39; P<0.001)

Primary safety outcome

Non-procedure related major bleeding or clinically relevant nonmajor bleeding, which was a combination of ISTH major and clinically relevant non-major bleeding (excluding events related to the procedure).

Superiority

3.9% vs. 5.0% (HR 0.44; 95% CI 0.33 to 0.59; P<0.001)

Secondary Outcomes

ISTH major bleed including procedure-related bleeding

Non-inferiority with 5.25% margin

3.9% vs. 5.0% (difference -1.1%; 97.5% one-sided upper confidence limit 1.0; HR 0.77; 95% CI 0.48 to 1.24; P<0.001)

Subgroup Analysis

There were no differences in the primary endpoints and secondary endpoint by age, sex, CHA2DS2-VASC score, HAS-BLED score, and AF type.

Additional End Points

HRs only shown for comparisons that do not include the null. Adapted from Figure S1, Figure S4, Table S17, and Table S19.

Anticoagulation use at the end of follow-up

10.1% vs. 84.8%

~95% of patients on anticoagulation received DOACs and only ~5% received warfarin or similar agents.

Use of antiarrhythmic medications

See Figure S4

Baseline: ~80% in each arm

36 months: ~30% in each arm

All-cause mortality

3.8% vs. 4.5%

CV mortality: 1.2% vs 1.3%

Non-CV mortality: 1.9% vs. 2.6%

Unexplained mortality: 0.8% vs. 0.7%

Ischemic stroke or systemic embolism

1.5% vs. 1.5%

Stroke

1.6% vs. 2.0%

Ischemic: 1.2% vs. 1.3%

Hemorrhagic: 0.4% vs. 0.4%

Disabling: 0 vs 0.3%

Non-disabling: 0.8% vs. 1.1%

Systemic embolism

0.3% vs. 0.1%

TIA

1.6% vs. 1.5%

ISTH bleeding

9.5% vs. 18.1% (HR 0.50; 95% CI 0.38, 0.66)

Major: 3.9% vs. 5.0%

Clinically-relevant nonmajor bleeding: 6.0% vs. 14.6% (HR 0.39; 95% CI 0.28, 0.55)

Pericardial effusion requiring intervention

0.3% vs. 0.7%

Sinus rhythm at follow-up

12 mo: 80.3% vs. 83.5%

24 mo: 77.9% vs. 77.2%

36 mo: 75.2% vs. 77.7%

Other clinical events

Repeat ablation: 14.4% vs. 12.9%

Medical/electrical cardioversion: 23.0% vs. 21.3%

New onset AF or atrial tachycardia: 12.6% vs. 13.4%

Resumed antiarrhythmic drug: 9.7% vs. 8.8%

Increase in dose of antiarrhythmic drug: 9.2% vs. 9.4%

Adverse Events

An extensive list of serious adverse events is presented in Table S18 on PDF page 35 of the supplementary appendix.

LAA closure arm events

Device-related serious adverse events: 0.6%

LAA closure procedure-related serious adverse events: 2.8%

Hospitalization for adverse event

38.7% vs. 38.8%

Criticisms

• Pulse field ablation was not available during the study window.
• Did not include persons with more advanced HF symptoms or LVEF ≤30%.
• Open label design.
• Limited follow up.
• Did not compare against LAA occlusion or anticogulation without AF ablation.

Funding

Boston Scientific