INTRODUCTION: Observational studies have shown low bleeding rates in patients with atrial fibrillation (AF) treated by left atrial appendage closure (LAAC); however, data from randomized studies are lacking. This study compared bleeding events among patients with AF treated by LAAC and nonvitamin K anticoagulants (NOAC). METHODS: The Prague-17 trial was a prospective, multicenter, randomized trial that compared LAAC to NOAC in high-risk AF patients. The primary endpoint was a composite of a cardioembolic event, cardiovascular death, and major and clinically relevant nonmajor bleeding (CRNMB) defined according to the International Society on Thrombosis and Hemostasis (ISTH). RESULTS: The trial enrolled 402 patients (201 per arm), and the median follow-up was 3.5 (IQR 2.6-4.2) years. Bleeding occurred in 24 patients (29 events) and 32 patients (40 events) in the LAAC and NOAC groups, respectively. Six of the LAAC bleeding events were procedure/device-related. In the primary intention-to-treat analysis, LAAC was associated with similar rates of ISTH major or CRNMB (sHR 0.75, 95% CI 0.44-1.27, p = 0.28), but with a reduction in nonprocedural major or CRNMB (sHR 0.55, 95% CI 0.31-0.97, p = 0.039). This reduction for nonprocedural bleeding with LAAC was mainly driven by a reduced rate of CRNMB (sHR for major bleeding 0.69, 95% CI 0.34-1.39, p = .30; sHR for CRNMB 0.43, 95% CI 0.18-1.03, p = 0.059). History of bleeding was a predictor of bleeding during follow-up. Gastrointestinal bleeding was the most common bleeding site in both groups. CONCLUSION: During the 4-year follow-up, LAAC was associated with less nonprocedural bleeding. The reduction is mainly driven by a decrease in CRNMB.

1st Department of Internal Medicine Faculty of Medicine University Hospital Hradec Kralove Charles University Prague Prague Czech Republic

Cardiocenter 2nd Internal Clinic Cardiology and Angiology General Faculty Hospital Charles University Prague Czech Republic

Cardiocenter Institute of Clinical and Experimental Medicine Prague Czech Republic

Department of Cardiology 3rd Faculty of Medicine University Hospital Kralovske Vinohrady Charles University Prague Czech Republic

Department of Cardiology Cardiocenter Hospital Podlesí a s Trinec Czech Republic

Department of Cardiology Cardiocenter Na Homolce Hospital Prague Czech Republic

Department of Cardiology Cardiocenter University Hospital Olomouc Olomouc Czech Republic

Department of Cardiology Krajská zdravotni a s Masaryk Hospital and UJEP Usti nad Labem Czech Republic

Department of Cardiology University Hospital and Faculty of Medicine Pilsen Pilsen Czech Republic

Department of Internal Medicine and Cardiology Faculty of Medicin University Hospital Ostrava Ostrava Czech Republic

Department of Internal Medicine and Cardiology University Hospital Brno and Medical Faculty of Masaryk University Brno Czech Republic

Icahn School of Medicine at Mount Sinai Helmsley Electrophysiology Center New York New York USA

Institute of Biostatistics and Analyses Masaryk University Brno Czech Republic

Zobrazit více v PubMed

Segal JB, McNamara RL, Miller MR, et al. Prevention of thromboembolism in atrial fibrillation. A meta-analysis of trials of anticoagulants and antiplatelet drugs. J Gen Intern Med. 2000;15(1):56-67.

Ruff CT, Giugliano RP, Braunwald E, et al. Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials. Lancet. 2014;383(9921):955-962.

Brouwer TF, Whang W, Kuroki K, Halperin JL, Reddy VY. Net clinical benefit of left atrial appendage closure versus warfarin in patients with atrial fibrillation: a pooled analysis of the randomized PROTECT-AF and PREVAIL studies. J Am Heart Assoc. 2019;8(23):e013525.

Osmancik P, Herman D, Neuzil P, et al. Left atrial appendage closure versus direct oral anticoagulants in high-risk patients with atrial fibrillation. JACC. 2020;75(25):3122-3135.

Osmancik P, Herman D, Neuzil P, et al. 4-year outcomes after left atrial appendage closure versus nonwarfarin oral anticoagulation for atrial fibrillation. JACC. 2022;79:1-14.

Pisters R, Lane DA, Nieuwlaat R, de Vos CB, Crijns HJGM, Lip GYH. A novel user-friendly score (HAS-BLED) To assess 1-year risk of major bleeding in patients with atrial fibrillation. Chest. 2010;138(5):1093-1100.

Schulman S, Kearon C, Subcommittee on Control of Anticoagulation of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. J Thromb Haemostasis. 2005;3(4):692-694.

Price MJ, Reddy VY, Valderrábano M, et al. Bleeding outcomes after left atrial appendage closure compared with long-term warfarin. JACC Cardiovasc Interv. 2015;8(15):1925-1932.

Hildick-Smith D, Landmesser U, Camm AJ, et al. Left atrial appendage occlusion with the Amplatzer™ Amulet™ device: full results of the prospective global observational study. Eur Heart J. 2020;41:2894-2901.

Lip GYH, Connolly S, Yusuf S, et al. Modification of outcomes with aspirin or apixaban in relation to CHADS(2) and CHA(2)DS(2)-VASc scores in patients with atrial fibrillation: a secondary analysis of the AVERROES study. Circ: Arrhythmia Electrophysiol. 2013;6(1):31-38.

Lopes RD, Al-Khatib SM, Wallentin L, et al. Efficacy and safety of apixaban compared with warfarin according to patient risk of stroke and of bleeding in atrial fibrillation: a secondary analysis of a randomised controlled trial. Lancet. 2012;380(9855):1749-1758.

Chatterjee S, Sardar P, Giri JS, Ghosh J, Mukherjee D. Treatment discontinuations with new oral agents for long-term anticoagulation: insights from a meta-analysis of 18 randomized trials including 101,801 patients. Mayo Clin Proc. 2014;89(7):896-907.

Gallagher AM, Rietbrock S, Plumb J, van Staa TP. Initiation and persistence of warfarin or aspirin in patients with chronic atrial fibrillation in general practice: do the appropriate patients receive stroke prophylaxis? J Thromb Haemostasis. 2008;6(9):1500-1506.

Flaker GC, Eikelboom JW, Shestakovska O, et al. Bleeding during treatment with aspirin versus apixaban in patients with atrial fibrillation unsuitable for warfarin: the apixaban versus acetylsalicylic acid to prevent stroke in atrial fibrillation patients who have failed or are unsuitable for vitamin K antagonist treatment (AVERROES) trial. Stroke. 2012;43(12):3291-3297.

Lakkireddy D, Thaler D, Ellis CR, et al. Amplatzer amulet left atrial appendage occluder versus watchman device for stroke prophylaxis (Amulet IDE): a randomized, controlled trial. Circulation. 2021;144(19):1543-1552.

Lane D, Meyerhoff J, Rohner U, Lip G. Patients' perceptions of atrial fibrillation, stroke risk, and oral anticoagulation treatment: an international survey. TH Open. 2018;02(3):e233-e241.

Wilke T, Bauer S, Mueller S, Kohlmann T, Bauersachs R. Patient preferences for oral anticoagulation therapy in atrial fibrillation: a systematic literature review. Patient-Patient Cent Outcomes Res. 2017;10(1):17-37.

Reddy VY, Doshi SK, Kar S, et al. 5-year outcomes after left atrial appendage closure. JACC. 2017;70(24):2964-2975.

Whitlock RP, Belley-Cote EP, Paparella D, et al. Left atrial appendage occlusion during cardiac surgery to prevent stroke. N Engl J Med. 2021;384(22):2081-2091.