Incidence and clinical impact of major bleeding following left atrial appendage occlusion: insights from the Amplatzer Amulet Observational Post-Market Study

Abstract

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. ClinicalTrials.gov Identifier: NCT02447081. https://ichgcp.net/clinical-trials-registry/NCT02447081.

Conflict of interest statement

A. Aminian has served as a proctor for Abbott and is a consultant for Abbott. O. De Backer has received institutional research grants and consultation fees from Abbott. J.E. Nielsen-Kudsk has served as a proctor for Abbott and is a consultant for Abbott and Boston Scientific. P. Mazzone has served as a consultant for Abbott, Boston Scientific, and Medtronic. S. Berti has served as a proctor for Abbott. S. Fischer has served as a proctor for Biotronik and Boston Scientific and is a consultant for Abbott. J. Lund has served as a proctor for Abbott. M. Montorfano has served as a proctor for Abbott, Boston Scientific, and Edwards Lifesciences. X. Freixa has served as a proctor and consultant for Abbott. R. Gage is an employee of Abbott. H.C. Diener has served as editor of Aktuelle Neurologie, Arzneimitteltherapie, as co-editor of Cephalalgia and on the editorial board of Lancet Neurology, Stroke, European Neurology and Cerebrovascular Disorders. H.C. Diener chairs the Treatment Guidelines Committee of the German Society of Neurology and contributed to the EHRA and ESC guidelines for the treatment of AF. B. Schmidt has served as a consultant for Boston Scientific and Medtronic. The other author has no conflicts of interest to declare.

Figures

Figure 1

MB location and severity. A) The majority of pre-LAAO MBs were gastrointestinal or intracranial. B) Post LAAO, 67 of the 140 MBs were gastrointestinal, accounting for half of BARC 3 events and 18.2% of fatal BARC 5 events. Intracranial MBs occurred 18 times, with fatal BARC 5 events most often resulting from intracranial bleeds.

Figure 2

Cumulative and landmark analyses of major bleeding events after LAAO. A) During two years of follow-up, a total of 140 MB events occurred in 110 subjects, corresponding to an annualised rate of 7.2% and 10.1% of all patients, respectively. B) Three intervals: from LAAO procedure to day 7 (periprocedural), from day 8 to 6 months, during which most patients were still under an antithrombotic regimen, and long-term follow-up (>6 months) when most patients were maintained on a restricted antithrombotic regimen (single antiplatelet or no antithrombotic medication).

Figure 3

Association of post-LAAO major bleeding with clinical outcomes. Kaplan-Meier analyses up to two years post LAAO comparing all-cause mortality (A), CV mortality (B) and ischaemic stroke/TIA (C) between patients with and without MB events following LAAO. Both all-cause and CV mortality rates at two years were significantly higher in patients with an MB event post LAAO. The rate of ischaemic stroke or TIA was similar in patients with and without MB, with an annualised rate of ischaemic stroke of 1.7%/year and 2.2%/year, respectively (p=0.640).

Figure 4

Association of major bleeding location with all-cause mortality. Patients were stratified according to MB location after LAAO: intracranial (IC), gastrointestinal (GI) and non-GI/non-IC. The cumulative mortality incidence for each subgroup is shown and compared to patients without MB.

Figure 5

Major bleed timing, severity, and location relative to mortality. The 41 patients who had an MB and died over follow-up (grey lines) are shown. Periprocedural MBs were rarely fatal, with only one of the 30 patients with a periprocedural MB dying within 30 days of LAAO. Nineteen patients died within 30 days following an MB, with many of the late deaths occurring shortly after an IC or GI event.