##common.pageHeaderLogo.altText##

Original article

Vol. 155 No. 10 (2025)

Safety and effectiveness of left atrial appendage occlusion in patients with atrial fibrillation and high bleeding risk: a cardinality-matched comparison with direct oral anticoagulation on long-term stroke and bleeding rates

Cite this as:
Swiss Med Wkly. 2025;155:4288
Published
15.10.2025

Summary

STUDY AIMS: Left atrial appendage occlusion (LAAO) is an accepted alternative stroke prevention strategy for patients with atrial fibrillation (AF) and contraindications to oral anticoagulation despite the lack of randomised data in this population. This study aims to compare the outcomes of LAAO and direct oral anticoagulation (DOAC) therapy in patients with high bleeding risk.

METHODS: This cardinality-matched analysis comprised data from the Beat-AF and Swiss-AF cohorts (n = 3960; enrolment from 2010 to 2014 and from 2014 to 2017, respectively), along with the Zurich LAAO Registry (n = 535; patients included between 2010 and 2023). The primary endpoint was a composite of stroke, cardiovascular death or major bleeding. The individual components constituted the secondary endpoints. Time-dependent cumulative incidence curves were constructed and a competing risk analysis was included.

RESULTS: After matching, 478 patients with a DOAC score ≥8 and 159 patients with previous major bleeding were compared in a 1:1 and 1:2 ratio, respectively, regarding their stroke prevention strategy (DOAC versus LAAO). After a median follow-up time of 4.9 years (interquartile range [IQR]: 2.2–6.1) in all patients with a DOAC score ≥8 and 4.4 years (IQR: 2.0–6.0) in all patients with previous major bleeding, there were no significant differences in the primary endpoint (hazard ratio [HR]: 0.88, 95% confidence interval [CI]: 0.67–1.14, p = 0.33 and HR: 0.79, 95% CI: 0.50–1.27, p = 0.33) and in the rates of stroke (HR: 0.74, 95% CI: 0.39–1.42, p = 0.36 and HR: 1.09, 95% CI: 0.33–3.62, p = 0.89) and cardiovascular death (HR: 0.97, 95% CI: 0.68–1.38, p = 0.85 and HR: 0.91, 95% CI: 0.50–1.64, p = 0.74). The rate of major bleedings was significantly lower in the LAAO group of both cohorts (HR: 0.55, 95% CI: 0.32–0.94, p = 0.029 and HR: 0.32, 95% CI: 0.13–0.79, p = 0.013).

CONCLUSION: In this high bleeding risk population, LAAO was associated with similar effectiveness in preventing atrial fibrillation-related stroke and cardiovascular death and significantly lower rates of major bleeding compared to DOAC therapy. This strengthens the value of LAAO as an alternative stroke prevention strategy for patients at high risk of bleeding.

References

  1. 1. Hindricks G, Potpara T, Dagres N, Arbelo E, Bax JJ, Blomström-Lundqvist C, et al.; ESC Scientific Document Group. 2020 ESC Guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS): The Task Force for the diagnosis and management of atrial fibrillation of the European Society of Cardiology (ESC) Developed with the special contribution of the European Heart Rhythm Association (EHRA) of the ESC [Erratum in: Eur Heart J. 2021 Oct 21;42] [40] [:4194. doi: 10.1093/eurheartj/ehab648. PMID: 32860505]. Eur Heart J. 2021 Feb;42(5):373–498. 10.1093/eurheartj/ehaa945 10.1093/eurheartj/ehaa612
  2. 2. Van Gelder IC, Rienstra M, Bunting KV, Casado-Arroyo R, Caso V, Crijns HJ, et al.; ESC Scientific Document Group. 2024 ESC Guidelines for the management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS) [Erratum in: Eur Heart J. 2025 Jul 07:ehaf306. doi: 10.1093/eurheartj/ehaf306. PMID: 39210723]. Eur Heart J. 2024 Sep;45(36):3314–414. 10.1093/eurheartj/ehae176 10.1093/eurheartj/ehae176
  3. 3. Hart RG, Benavente O, McBride R, Pearce LA. Antithrombotic therapy to prevent stroke in patients with atrial fibrillation: a meta-analysis. Ann Intern Med. 1999 Oct;131(7):492–501. 10.7326/0003-4819-131-7-199910050-00003
  4. 4. Holmes DR Jr, Doshi SK, Kar S, Price MJ, Sanchez JM, Sievert H, et al. Left Atrial Appendage Closure as an Alternative to Warfarin for Stroke Prevention in Atrial Fibrillation: A Patient-Level Meta-Analysis. J Am Coll Cardiol. 2015 Jun;65(24):2614–23. 10.1016/j.jacc.2015.04.025
  5. 5. Reddy VY, Sievert H, Halperin J, Doshi SK, Buchbinder M, Neuzil P, et al.; PROTECT AF Steering Committee and Investigators. Percutaneous left atrial appendage closure vs warfarin for atrial fibrillation: a randomized clinical trial [Erratum in: JAMA. 2015 Mar 10;313] [10] [:1061. PMID: 25399274]. JAMA. 2014 Nov;312(19):1988–98. 10.1001/jama.2014.15192
  6. 6. Holmes DR Jr, Kar S, Price MJ, Whisenant B, Sievert H, Doshi SK, et al. Prospective randomized evaluation of the Watchman Left Atrial Appendage Closure device in patients with atrial fibrillation versus long-term warfarin therapy: the PREVAIL trial [Erratum in: J Am Coll Cardiol. 2014 Sep 16;64] [11] [:1186. PMID: 24998121]. J Am Coll Cardiol. 2014 Jul;64(1):1–12. 10.1016/j.jacc.2014.04.029
  7. 7. Osmancik P, Herman D, Neuzil P, Hala P, Taborsky M, Kala P, et al.; PRAGUE-17 Trial Investigators. 4-Year Outcomes After Left Atrial Appendage Closure Versus Nonwarfarin Oral Anticoagulation for Atrial Fibrillation. J Am Coll Cardiol. 2022 Jan;79(1):1–14. 10.1016/j.jacc.2021.10.023
  8. 8. Wazni OM, Saliba WI, Nair DG, Marijon E, Schmidt B, Hounshell T, et al.; OPTION Trial Investigators. Left Atrial Appendage Closure after Ablation for Atrial Fibrillation. N Engl J Med. 2025 Apr;392(13):1277–87. 10.1056/NEJMoa2408308
  9. 9. Nielsen-Kudsk JE, Korsholm K, Damgaard D, Valentin JB, Diener HC, Camm AJ, et al. Clinical Outcomes Associated With Left Atrial Appendage Occlusion Versus Direct Oral Anticoagulation in Atrial Fibrillation. JACC Cardiovasc Interv. 2021 Jan;14(1):69–78. 10.1016/j.jcin.2020.09.051
  10. 10. Gloekler S, Fürholz M, de Marchi S, Kleinecke C, Streit SR, Buffle E, et al. Left atrial appendage closure versus medical therapy in patients with atrial fibrillation: the APPLY study. EuroIntervention. 2020 Oct;16(9):e767–74. 10.4244/EIJ-D-20-00201
  11. 11. Nietlispach F, Moarof I, Taramasso M, Maisano F, Meier B. Left atrial appendage occlusion. EuroIntervention. 2017;13(AA):AA78-AA84. doi: 10.4244/EIJ-D-17-00412. PMID: 28942389.
  12. 12. Holmes DR, Reddy VY, Buchbinder M, Stein K, Elletson M, Bergmann MW, et al. The Assessment of the Watchman Device in Patients Unsuitable for Oral Anticoagulation (ASAP-TOO) trial. Am Heart J. 2017 Jul;189:68–74. 10.1016/j.ahj.2017.03.007
  13. 13. Conen D, Rodondi N, Mueller A, Beer J, Auricchio A, Ammann P, et al. Design of the Swiss Atrial Fibrillation Cohort Study (Swiss-AF): structural brain damage and cognitive decline among patients with atrial fibrillation. Swiss Med Wkly. 2017 Jul;147(2728):w14467. 10.4414/smw.2017.14467
  14. 14. Glikson M, Wolff R, Hindricks G, Mandrola J, Camm AJ, Lip GY, et al.; ESC Scientific Document Group. EHRA/EAPCI expert consensus statement on catheter-based left atrial appendage occlusion - an update. Europace. 2020 Feb;22(2):184. 10.1093/europace/euz258
  15. 15. Gilhofer TS, Schweiger V, Gehler M, Bokemeyer V, Chen M, Candreva A, et al. Long-term outcomes after echocardiography versus fluoroscopy-guided left atrial appendage closure: is there still a role for a simplified approach? Catheter Cardiovasc Interv. 2024 Aug;104(2):343–55. 10.1002/ccd.31126
  16. 16. Aggarwal R, Ruff CT, Virdone S, Perreault S, Kakkar AK, Palazzolo MG, et al. Development and Validation of the DOAC Score: A Novel Bleeding Risk Prediction Tool for Patients With Atrial Fibrillation on Direct-Acting Oral Anticoagulants. Circulation. 2023 Sep;148(12):936–46. 10.1161/CIRCULATIONAHA.123.064556
  17. 17. 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 Haemost. 2005 Apr;3(4):692–4. 10.1111/j.1538-7836.2005.01204.x
  18. 18. Joglar JA, Chung MK, Armbruster AL, Benjamin EJ, Chyou JY, Cronin EM, et al.; Peer Review Committee Members. 2023 ACC/AHA/ACCP/HRS Guideline for the Diagnosis and Management of Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2024 Jan;149(1):e1–156. 10.1161/CIR.0000000000001263 doi: https://doi.org/10.1161/CIR.0000000000001193
  19. 19. Potpara T, Grygier M, Häusler KG, Nielsen-Kudsk JE, Berti S, Genovesi S, et al. Practical guide on left atrial appendage closure for the non-implanting physician: an international consensus paper. Europace. 2024 Mar;26(4):euae035. 10.1093/europace/euae142 doi: https://doi.org/10.1093/europace/euae035
  20. 20. Connolly SJ, Ezekowitz MD, Yusuf S, Eikelboom J, Oldgren J, Parekh A, et al.; RE-LY Steering Committee and Investigators. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009 Sep;361(12):1139–51. doi: https://doi.org/10.1056/NEJMoa0905561
  21. 21. Connolly SJ, Eikelboom J, Joyner C, Diener HC, Hart R, Golitsyn S, et al.; AVERROES Steering Committee and Investigators. Apixaban in patients with atrial fibrillation [Erratum in: N Engl J Med. 2010 Nov 4;363] [19] [:1877. PMID: 19717844]. N Engl J Med. 2011 Mar;364(9):806–17. 10.1056/NEJMoa0905561 doi: https://doi.org/10.1056/NEJMoa1007432
  22. 22. Granger CB, Alexander JH, McMurray JJ, Lopes RD, Hylek EM, Hanna M, et al.; ARISTOTLE Committees and Investigators. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2011 Sep;365(11):981–92. 10.1056/NEJMoa1107039
  23. 23. Patel MR, Mahaffey KW, Garg J, Pan G, Singer DE, Hacke W, et al.; ROCKET AF Investigators. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med. 2011 Sep;365(10):883–91. 10.1056/NEJMoa1009638
  24. 24. Chang G, Xie Q, Ma L, Hu K, Zhang Z, Mu G, et al. Accuracy of HAS-BLED and other bleeding risk assessment tools in predicting major bleeding events in atrial fibrillation: A network meta-analysis. J Thromb Haemost. 2020 Apr;18(4):791–801. 10.1111/jth.14692
  25. 25. Pisters R, Lane DA, Nieuwlaat R, de Vos CB, Crijns HJ, Lip GY. A novel user-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in patients with atrial fibrillation: the Euro Heart Survey. Chest. 2010 Nov;138(5):1093–100. 10.1378/chest.10-0134
  26. 26. Elsheikh S, Alobaida M, Bucci T, Buckley BJ, Gupta D, Irving G, et al. Left Atrial Appendage Occlusion versus Direct Oral Anticoagulants in the Prevention of Ischaemic Stroke in Patients with Atrial Fibrillation. Cerebrovasc Dis. 2025;54(1):81–88. 10.1159/000536546
  27. 27. Gilhofer T, Bokemeyer V, Schweiger V, Gehler M, Michel J, Chen M, et al. Long-Term Outcome of Patients with Atrial Fibrillation and High Risk of Stroke Treated with Oral Anticoagulation or Left Atrial Appendage Occlusion: A Cardinality Matched Analysis. Cardiology. 2024 Oct:1–15. 10.1159/000541907; Epub ahead of print.
  28. 28. Kramer A, Patti G, Nielsen-Kudsk JE, Berti S, Korsholm K. Left Atrial Appendage Occlusion and Post-procedural Antithrombotic Management. J Clin Med. 2024 Jan;13(3):803. 10.3390/jcm13030803
  29. 29. Gilhofer TS, Nestelberger T, Kang M, Inohara T, Alfadhel M, McAlister C, et al. Stroke Prevention With Left Atrial Appendage Closure in Patients With Atrial Fibrillation and Prior Intracranial Hemorrhage. CJC Open. 2023 Mar;5(6):404–11. 10.1016/j.cjco.2023.03.004
  30. 30. Della Rocca DG, Magnocavallo M, Di Biase L, Mohanty S, Trivedi C, Tarantino N, et al. Half-Dose Direct Oral Anticoagulation Versus Standard Antithrombotic Therapy After Left Atrial Appendage Occlusion. JACC Cardiovasc Interv. 2021 Nov;14(21):2353–64. 10.1016/j.jcin.2021.07.031
  31. 31. Piccini JP, Patel MR, Steffel J, Ferdinand K, Van Gelder IC, Russo AM, et al.; OCEANIC-AF Steering Committee and Investigators. Asundexian versus Apixaban in Patients with Atrial Fibrillation. N Engl J Med. 2025 Jan;392(1):23–32. 10.1056/NEJMoa2407105
  32. 32. Lip GY, Nieuwlaat R, Pisters R, Lane DA, Crijns HJ. Refining clinical risk stratification for predicting stroke and thromboembolism in atrial fibrillation using a novel risk factor-based approach: the euro heart survey on atrial fibrillation. Chest. 2010 Feb;137(2):263–72. 10.1378/chest.09-1584
  33. 33. Landmesser U, Skurk C, Tzikas A, Falk V, Reddy VY, Windecker S. Left atrial appendage closure for stroke prevention in atrial fibrillation: current status and perspectives. Eur Heart J. 2024 Aug;45(32):2914–32. 10.1093/eurheartj/ehae398