Background: Major bleeding (MB) events are independent predictors of mortality after cardiac interventional procedures. The clinical relevance of MB following left atrial appendage occlusion (LAAO) remains unclear.

Aims: This study aimed to investigate the incidence and clinical impact of MB after LAAO in a real-world population at high risk for bleeding and contraindicated to anticoagulation.

Methods: The two-year results of the Amplatzer Amulet Observational Post-Market Study were analysed. An independent committee adjudicated MBs according to the Bleeding Academic Research Consortium scale. Cox proportional hazards regression identified variables associated with MB events and mortality.

Results: The MB rate was 7.2%/year, with a rate of 10.1%/year during year one, decreasing to 4.0%/year over year two. The most common bleeding location was gastrointestinal, accounting for 48% of MBs. Pre-LAAO MB was associated with an increased risk for post-LAAO MB (HR 2.34, 95% CI: 1.37-3.99). The occurrence of post-LAAO MB was associated with increased mortality (37.3% vs 12.7%; p<0.0001), driven mainly by events occurring beyond the periprocedural period. The annualised rate of ischaemic stroke or TIA was similar in patients with and without MB (2.3% vs 3.3%; p=0.446). MB post LAAO was a strong independent predictor of mortality (HR 3.07, 95% CI: 2.15-4.40).

Conclusions: In real-world patients at high bleeding risk, MB following LAAO was not uncommon and associated with a significant increase in mortality, without increasing the risk of stroke.