Strategy Optimization for a Combined Procedure in Patients With Atrial Fibrillation: The COMBINATION Randomized Clinical Trial.

IMPORTANCE

The optimal strategy of combining left atrial appendage occlusion (LAAO) with catheter ablation (CA) in patients with atrial fibrillation (AF) during a single procedure remains unclear.

OBJECTIVE

To determine the effects of ablation-first vs occlusion-first strategies on long-term clinical outcomes among patients with atrial fibrillation undergoing a combined LAAO and CA procedure.

DESIGN, SETTING, AND PARTICIPANTS: The prospective, multicenter COMBINATION randomized clinical trial was conducted in 14 high-volume centers in China. Enrollment of patients with nonvalvular AF referred for the combined procedure began on July 24, 2020, and concluded on January 20, 2022.

INTERVENTIONS

Patients were randomly assigned to either the ablation-first group or the occlusion-first group. Outcomes of LAAO using an occlusion device and CA using a contact force-sensing catheter following different combination strategies during long-term follow-up were evaluated.

MAIN OUTCOMES AND MEASURES

The primary end point was a composite of thromboembolic events including stroke or transient ischemic attack, device-related thrombus (DRT), clinically relevant bleeding, and cardiovascular rehospitalization or death. Freedom from AF or atrial tachyarrhythmia (ATA) after a single procedure without antiarrhythmic drugs, at both 1 year and long-term follow-up, was also evaluated.

RESULTS

Of the 202 patients enrolled, 194 (96.0%) completed the trial (97 in the ablation-first group and 97 in the occlusion-first group). The mean (SD) age of the cohort was 67.3 (9.2) years, and 110 patients (56.7%) were male. All procedures achieved acute successful LAAO and restoration of sinus rhythm, with similar incidences of periprocedural complications. Compared with the ablation-first group, the occlusion-first group exhibited significantly higher event-free survival of the primary end point (83.5% vs 71.1%; hazard ratio [HR], 0.53 [95% CI, 0.29-0.95]; log-rank P = .04) during the median 2.5 (IQR, 2.3-2.8) years of follow-up. Subgroup analysis indicated that male patients and those with higher CHA2DS2-VASc scores (a composite of factors associated with stroke risk; higher scores indicate higher risk) were at lower risk of thromboembolic events. Rates of long-term freedom from AF (77.3% vs 63.5%; HR, 0.58 [95% CI, 0.34-0.97]; log-rank P = .04) and from ATA (70.1% vs 55.7%; HR, 0.62 [95% CI, 0.39-0.99]; log-rank P = .04) were higher in the occlusion-first group vs the ablation-first group. Additionally, a higher incidence of chronic peridevice leak (15 [15.5%] vs 5 [5.2%]; P = .03) and DRT (8 [8.2%] vs 1 [1.0%]; P = .04) was observed in the ablation-first group vs the occlusion-first group.

CONCLUSIONS AND RELEVANCE

In this randomized clinical trial, the occlusion-first approach was superior due to its higher event-free survival of the primary end point and long-term freedom from ATA. These findings suggest that the occlusion-first approach should be recommended for combined procedures with plug-like device implantation.

TRIAL REGISTRATION

Chinese Clinical Trial Registry Identifier: ChiCTR2000031486.