Catheter-based closure of the left atrial appendage (LAA) was found to be not noninferior to physician-directed best medical care for the primary composite endpoint of stroke, systemic embolism, major bleeding, or cardiovascular or unexplained death among patients with atrial fibrillation (AFib) and a high risk of stroke or bleeding, according to results of the CLOSURE-AF trial published March 18 in NEJM.

The multicenter trial, conducted in Germany, randomized 912 patients (mean age, 78 years; 39% women; 94% White) with AFib and a high risk of stroke (mean CHA2DS2-VASc score 5.2) and bleeding (mean HAS-BLED score 3.0) to LAA closure (n=446) or physician-directed best medical care including direct oral anticoagulants (n=442).

Results during a median follow-up of three years found that a first primary endpoint occurred in 155 patients in the device arm and 127 patients in the medical-therapy arm, for an incidence rate of 16.8 vs. 13.3 per 100 patient-years). The difference in restricted mean survival time was –0.36 years (p=0.44 for noninferiority).

For the individual components of the primary outcome, 27 patients in both arms experienced a stroke (2.6 vs. 2.7 per 100 patient-years). For the device vs. medical-therapy arms, respectively, the incidence rates for systemic embolism were 0.3 vs. 0.1 per 100 patient-years; major bleeding 7.4 vs. 6.2 per 100 patient-years; cardiovascular or unexplained death 9.5 vs. 7.7 per 100 patient-years.

Serious adverse events occurred in 83% of the device arm and 78% of the medical-therapy arm.

LAA closure was successful in 98% of cases, with 6% of patients experiencing periprocedural complications within seven days, including leaks (20 cases), major bleeding (18 patients) and pericardial tamponade (five cases), as well as two periprocedural deaths and one device embolization that led to surgical retrieval of the device.

“Although catheter-based [LAA] closure might appear to be a good option in older patients and patients with coexisting medical conditions who are at a high risk for bleeding,” write study authors Ulf Landmesser, MD; Carsten Skurk, MD; et al., “this patient group is particularly vulnerable to periprocedural complications and early nonprocedural major bleeding.”

“The message for the clinician is clear,” writes Petr Widimský, MD, DSc, in an accompanying editorial comment. “[LAA] closure failed to fulfill its theoretical promise to become an alternative treatment to best medical therapy – at least for older patients such as those enrolled in the trial. Best individualized medical therapy should remain standard treatment for older patients.”

“This is an evolving field,” says ACC Clinical Content Editor-in-Chief Fred M. Kusumoto, MD, FACC, “and we’re staying tuned for the results of the CHAMPION-AF trial, which is being presented in a late-breaking clinical trial session during ACC.26 in New Orleans.