A left atrial appendage (LAA) closure device provides long-term thromboembolic protection that is equivalent to direct oral anticoagulants after ablation for atrial fibrillation (AF), along with a lower risk of bleeding, according to the multicenter, randomized OPTION trial.

Based on this study, which is the first to compare LAA closure with oral anticoagulants for prevention of stroke after AF ablation, LAA closure should now be considered “an effective first-line option,” said Oussama M. Wazni, MD, chief of electrophysiology at the Cleveland Clinic.

In the open-label study conducted at 106 sites in 10 countries, 1600 patients with AF and a planned ablation were randomized. At least a moderate risk of stroke – a CHA₂DS₂-VASc score ≥ 2 in men and ≥ 3 in women — was an entry criterion.

In the LAA closure group, patients were treated with a proprietary device (WATCHMAN FLX, Boston Scientific). In the oral anticoagulant group, a currently marketed anticoagulant was selected by the treating investigator.

Non-inferiority established with high confidence

For the primary composite efficacy endpoint of all-cause death, stroke, and systemic embolism, rates at 36 months were similar in the LAA closure and anticoagulation groups (5.3% vs. 5.8%). This established the non-inferiority of LAA closure to anticoagulants with a high level of significance (p < .001).

For the primary safety endpoint of nonprocedural major bleeding or clinically relevant nonmajor bleeding, rates were lower in the LAA closure group than in the oral anticoagulant group (8.5% vs. 18.1 %; p <.001 for superiority), Wazni reported at the American Heart Association (AHA) Scientific Sessions in Chicago. The OPTION results were simultaneous published online in New England Journal of Medicine.

Of the 803 patients randomized to LAA closure, nine implantations were unsuccessful and 41 patients never received the device. In the oral anticoagulant group, one patient underwent LAA closure in error and 82 patients crossed over. At least 92% of patients in each group completed the 36-month follow-up.

Baseline characteristics in the two groups were comparable. The average age was about 69 years, and about a third of the patients were women. About 10% of patients have had a previous stroke or transient ischemic attack. Before ablation, approximately 40% had persistent AF and 60% had paroxysmal AF.

Rates for similar events in the two groups

Individual events in the primary composite efficacy endpoint were similar; no differences approach statistical significance. For the endpoint of mortality, for example, the rates of all-cause deaths (3.8% vs. 4.5%; p = .46), cardiovascular death (1.2% vs 1.3%; p = 0.94), and noncardiovascular death (1.9% vs 2.6%; p = .34) were all lower in the LAA closure group than in the anticoagulant group, but statistically comparable.

Rates of ischemic stroke in the LAA closure and anticoagulant groups were similar (1.2% vs 1.3%; p = .77), as are the rates of hemorrhagic stroke (0.4% vs. 0.4%). The rate of systemic embolism was higher in the LAA closure group than in the anticoagulant group, but the difference was not significant (0.3% vs 0.1%: p = .58).

All patients received anticoagulation after ablation, but the protocol called for discontinuation of anticoagulation in the LAA closure group after 90 days. This happened in about 80% of patients. At the end of 3 years, fewer patients in the LAA closure group than in the oral anticoagulant group remained on anticoagulation (10.1% vs. 84.8%).

There were no substantial differences in the primary efficacy or safety endpoints for subgroups defined by age (≥ 75 years vs < 75 years), sex, CHA₂DS₂– VASc score (2-3 vs 4-5 vs ≥ 6), HAS-BLED score (0 vs 1-2 vs ≥ 3) or AF type (paroxysmal vs persistent).

LAA was performed with ablation in 40% of patients

In the LAA closure group, 40% of patients underwent concurrent LAA ablation and closure; the remaining patients underwent LAA closure after ablation. Concomitant treatment could be an attractive strategy for patients undergoing LAA closure, Wazni pointed out.

The concurrent approach “has the potential to reduce procedural risks and recovery times for patients,” he said. “In one procedure, we have the potential to reduce the burden of AF and reduce the risk of stroke and bleeding.”

The use of LAA closure has been largely limited to patients who are not good candidates for anticoagulation, based on previous studies comparing LAA closure with warfarinthat prevailin which LAA closure did not meet noninferiority criteria for the composite efficacy outcome, said Manesh R. Patel, MD, chief of the Division of Cardiology at Duke University in Durham, North Carolina.

Closing the LAA with the device used in the OPTION trial is a “reasonable option” to discuss with patients, Patel said, but he emphasized that the risk of stroke should be enough to justify a prophylactic strategy. The OPTION trial was designed to evaluate LAA closure for stroke risk after patients underwent ablation, not for primary treatment. prevention of stroke in patients with AF.

There will likely be more debate about when LAA closure might be a better option than oral anticoagulants in the post-ablation AF patient, but Patel suggested that LAA closure might be specifically considered in patients with FA. heart failure.

The benefits of ablation for AF “are most evident in patients with heart failure,” he explained. “These patients are often at higher risk for stroke and systemic embolism and may be” ideal patients for this strategy.