Major bleeding (MB) was observed in nearly one-fifth of patients undergoing left atrial appendage occlusion  (LAAO) and was associated with higher rates of stroke and mortality over long-term follow-up. A secondary analysis of the Amulet IDE randomized clinical trial, published in JAMA Cardiology, evaluated the incidence, predictors, management, and outcomes of MB after LAAO in a high-risk population.

The trial enrolled 1,878 patients between 2016 and 2019, of whom 1,833 underwent attempted LAAO implantation at specialized centers and were followed for 5 years. MB, defined as Bleeding Academic Research Consortium (BARC) score ≥3, included overt bleeding with transfusion or a hemoglobin decrease ≥3 g/dL. Pooled analyses compared patients with and without MB.

Over a mean follow-up of 5 years, MB occurred in 331 patients (18.1%), corresponding to an annualized rate of 5.9%. Risk was highest within the first 6 months after LAAO (20.5% per year) and declined to 3.9% per year thereafter. Most events were nonprocedural (88.8%), with gastrointestinal bleeding accounting for 252 of 438 events. Patients with MB were older and had higher CHA₂DS₂-VASc and HAS-BLED scores, along with greater prevalence of diabetes, prior MB, and kidney disease. Independent predictors included increasing age (HR, 1.04; 95% CI, 1.02-1.06), female sex (HR, 1.25; 95% CI, 1.01-1.56), diabetes (HR, 1.26; 95% CI, 1.01-1.58), prior MB (HR, 1.93; 95% CI, 1.55-2.40), and kidney disease (HR, 2.15; 95% CI, 1.48-3.12). At the time of first MB, 47.1% of patients were not receiving antithrombotic therapy, and 92 patients experienced recurrent events.

MB was associated with higher rates of the composite of stroke, systemic embolism, or cardiovascular death (32.5% vs 18.0%; p < .001), driven by higher stroke (14.7% vs 6.6%) and cardiovascular death (24.4% vs 12.9%). All-cause mortality was also higher (49.2% vs 25.4%; p < .001), and fatal bleeding occurred in 25 patients (1.4%). 

MB was frequent in this high-risk population and was associated with baseline patient characteristics. The incidence was highest within the first 6 months after LAAO and declined thereafter. Most events were GI and occurred even among patients receiving minimal or no antithrombotic therapy. MB after LAAO was associated with higher rates of stroke and mortality.