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Thromb Haemost 2024; 124(11): 991-1002
DOI: 10.1055/s-0044-1786028
Coagulation and Fibrinolysis

Clinical Outcomes of Patients with Atrial Fibrillation who Survived from Bleeding Event: The Results from COOL-AF Thailand Registry

Arjbordin Winijkul
1   Division of Cardiology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
,
Pontawee Kaewkumdee
1   Division of Cardiology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
,
Ahthit Yindeengam
2   Her Majesty Cardiac Center, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
,
Gregory Y.H. Lip    *
3   Liverpool Centre for Cardiovascular Science, University of Liverpool, Liverpool John Moores University and Liverpool Heart and Chest Hospital, Liverpool, United Kingdom
4   Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
,
Rungroj Krittayaphong   *
1   Division of Cardiology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
› Institutsangaben Funding This study was funded by grants from the Health Systems Research Institute (HSRI) (grant no. 59-053), and the Heart Association of Thailand under the Royal Patronage of H.M. the King. None of the aforementioned funding sources influenced any aspect of this study or the decision of the authors to submit this manuscript for publication.
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Abstract

Background Bleeding events are often reported among patients with atrial fibrillation (AF), irrespective of antithrombotic use. This study is to determine clinical outcomes of patients with AF who survived from bleeding event.

Methods We analyzed data from COOL-AF (Cohort of Antithrombotic Use and Optimal International Normalized Ratio Levels in Patients with Atrial Fibrillation) Thailand registry. Outcomes of patients who experienced any bleeding were compared with patients who had never bleed. Time updated multivariate Cox-proportional hazard models were used to estimate the risk for clinical outcomes of patients with and without bleeding.

Results Of total 3,405 patients (mean age: 67.8 ± 11.3 years; 41.9% female) in COOL-AF registry, 609 patients (17.9%) reported bleeding event occurs and 568 patients (93.3%) survived though hospital discharge. Patients who survived major bleeding (n = 126) were at increased risk for both death (adjusted hazard ratio [HR]: 4.44, 95% confidence interval [CI]: 2.91–6.75, p < 0.001) and stroke/systemic embolism (adjusted HR: 4.49, 95% CI: 2.19–9.24, p < 0.001). Minor bleeding also increased subsequent death (adjusted HR: 2.13, 95% CI: 1.56–2.90, p < 0.001). Up to 30% of patients who survived major bleeding and 6.3% of minor bleedings discontinued oral anticoagulation. Discontinuation was associated with very high death rate (42.1%), whereas patients who resumed oral anticoagulation after bleeding had lower mortality (10%). The most common causes of death in patients who survived a bleeding event were not related to cardiovascular causes nor bleeding.

Conclusion Patients with AF who have bleeding events have an increased risk for subsequent death and stroke and systemic embolism. These patients should be identified as vulnerable clinically complex patients and require a holistic approach to their AF management.

Keywords

atrial fibrillation - bleeding - death - oral anticoagulants

Data Availability Statement

The dataset that was used to support the results and conclusion of this study are included within the manuscript. The data underlying this article will be shared on reasonable request to the corresponding author.


Authors' Contribution

All authors made substantial contributions to conception and design, acquisition of data, or analysis and interpretation of data; took part in drafting the article or revising it critically for important intellectual content; agreed to submit to the current journal; gave final approval of the version to be published; and agree to be accountable for all aspects of the work.


* These authors are Joint senior authors.


The review process for this paper was fully handled by Christian Weber, Editor in Chief.




Publikationsverlauf

Eingereicht: 22. Januar 2024

Angenommen: 18. März 2024

Artikel online veröffentlicht:
16. April 2024

© 2024. Thieme. All rights reserved.

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Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References

  • 1 January CT, Wann LS, Calkins H. et al. 2019 AHA/ACC/HRS focused update of the 2014 AHA/ACC/HRS Guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol 2019; 74 (01) 104-132
    CrossrefPubMedSuche in Google Scholar
  • 2 Hindricks G, Potpara T, Dagres N. 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. Eur Heart J 2021; 42 (05) 373-498
    CrossrefPubMedSuche in Google Scholar
  • 3 Chao TF, Joung B, Takahashi Y. et al. 2021 focused update consensus guidelines of the Asia Pacific Heart Rhythm Society on stroke prevention in atrial fibrillation: executive summary. Thromb Haemost 2022; 122 (01) 20-47
    Thieme ConnectPubMedSuche in Google Scholar
  • 4 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
    CrossrefPubMedSuche in Google Scholar
  • 5 Lopes LC, Spencer FA, Neumann I. et al. Systematic review of observational studies assessing bleeding risk in patients with atrial fibrillation not using anticoagulants. PLoS One 2014; 9 (02) e88131
    CrossrefPubMedSuche in Google Scholar
  • 6 Kim HK, Tantry US, Smith Jr SC. et al. The East Asian paradox: an updated position statement on the challenges to the current antithrombotic strategy in patients with cardiovascular disease. Thromb Haemost 2021; 121 (04) 422-432
    Thieme ConnectPubMedSuche in Google Scholar
  • 7 Rubboli A, Becattini C, Verheugt FW. Incidence, clinical impact and risk of bleeding during oral anticoagulation therapy. World J Cardiol 2011; 3 (11) 351-358
    CrossrefPubMedSuche in Google Scholar
  • 8 Meyre PB, Blum S, Hennings E. et al. Bleeding and ischaemic events after first bleed in anticoagulated atrial fibrillation patients: risk and timing. Eur Heart J 2022; 43 (47) 4899-4908
    CrossrefPubMedSuche in Google Scholar
  • 9 Carlin S, Eikelboom J. Restarting anticoagulation after major bleeding in patients with atrial fibrillation. Can J Cardiol 2024; ;S0828-282X(24)00019-9
    CrossrefPubMedSuche in Google Scholar
  • 10 Proietti M, Romiti GF, Romanazzi I. et al. Restarting oral anticoagulant therapy after major bleeding in atrial fibrillation: a systematic review and meta-analysis. Int J Cardiol 2018; 261: 84-91
    CrossrefPubMedSuche in Google Scholar
  • 11 Zhou Y, Guo Y, Liu D, Feng H, Liu J. Restarting of anticoagulation in patients with atrial fibrillation after major bleeding: a meta-analysis. J Clin Pharm Ther 2020; 45 (04) 591-601
    CrossrefPubMedSuche in Google Scholar
  • 12 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; 3 (04) 692-694
    CrossrefPubMedSuche in Google Scholar
  • 13 Ogawa H, Hamatani Y, Doi K. et al; Fushimi AF Registry Investigators. Sex-related differences in the clinical events of patients with atrial fibrillation—the Fushimi AF registry. Circ J 2017; 81 (10) 1403-1410
    CrossrefPubMedSuche in Google Scholar
  • 14 Bahuleyan CG, Namboodiri N, Jabir A. et al. One-year clinical outcome of patients with nonvalvular atrial fibrillation: insights from KERALA-AF registry. Indian Heart J 2021; 73 (01) 56-62
    CrossrefPubMedSuche in Google Scholar
  • 15 Krittayaphong R, Pumprueg S, Kaewkumdee P, Yindeengam A, Lip GY. Three-year outcomes of patients with non-valvular atrial fibrillation: the COOL-AF registry. J Geriatr Cardiol 2023; 20 (03) 163-173
    CrossrefPubMedSuche in Google Scholar
  • 16 Bassand JP, Accetta G, Camm AJ. et al; GARFIELD-AF Investigators. Two-year outcomes of patients with newly diagnosed atrial fibrillation: results from GARFIELD-AF. Eur Heart J 2016; 37 (38) 2882-2889
    CrossrefPubMedSuche in Google Scholar
  • 17 Chiang CE, Wang KL, Lip GYH. Stroke prevention in atrial fibrillation: an Asian perspective. Thromb Haemost 2014; 111 (05) 789-797
    Thieme ConnectPubMedSuche in Google Scholar
  • 18 Krittayaphong R, Winijkul A, Wongtheptien W. et al; COOL-AF Investigators. History of major bleeding predicts risk of clinical outcome of patients with atrial fibrillation: results from the COOL-AF registry. J Geriatr Cardiol 2020; 17 (04) 184-192
    PubMedSuche in Google Scholar
  • 19 Romiti GF, Proietti M, Bonini N. et al; GLORIA-AF Investigators. Clinical complexity domains, anticoagulation, and outcomes in patients with atrial fibrillation: a report from the GLORIA-AF registry phase II and III. Thromb Haemost 2022; 122 (12) 2030-2041
    Thieme ConnectPubMedSuche in Google Scholar
  • 20 Ogawa H, An Y, Ishigami K. et al; Fushimi AF Registry investigators. Long-term clinical outcomes after major bleeding in patients with atrial fibrillation: the Fushimi AF registry. Eur Heart J Qual Care Clin Outcomes 2021; 7 (02) 163-171
    CrossrefPubMedSuche in Google Scholar
  • 21 Krittayaphong R, Boonyapiphat T, Aroonsiriwattana S, Ngamjanyaporn P, Lip GYH. Causes of death of patients with non-valvular atrial fibrillation in Asians. PLoS One 2023; 18 (03) e0282455
    CrossrefPubMedSuche in Google Scholar
  • 22 Buck J, Fromings Hill J, Martin A. et al. Reasons for discontinuing oral anticoagulation therapy for atrial fibrillation: a systematic review. Age Ageing 2021; 50 (04) 1108-1117
    CrossrefPubMedSuche in Google Scholar
  • 23 Romiti GF, Pastori D, Rivera-Caravaca JM. et al. Adherence to the ‘atrial fibrillation better care’ pathway in patients with atrial fibrillation: impact on clinical outcomes-a systematic review and meta-analysis of 285,000 patients. Thromb Haemost 2022; 50 (04) 1108-1117
    PubMedSuche in Google Scholar
  • 24 Krittayaphong R, Winijkul A, Methavigul K, Lip GYH. Impact of achieving blood pressure targets and high time in therapeutic range on clinical outcomes in patients with atrial fibrillation adherent to the atrial fibrillation better care pathway: a report from the COOL-AF registry. J Am Heart Assoc 2023; 12 (03) e028463
    CrossrefPubMedSuche in Google Scholar
  • 25 Witt DM, Delate T, Garcia DA. et al. Risk of thromboembolism, recurrent hemorrhage, and death after warfarin therapy interruption for gastrointestinal tract bleeding. Arch Intern Med 2012; 172 (19) 1484-1491
    CrossrefPubMedSuche in Google Scholar
  • 26 Staerk L, Lip GY, Olesen JB. et al. Stroke and recurrent haemorrhage associated with antithrombotic treatment after gastrointestinal bleeding in patients with atrial fibrillation: nationwide cohort study. BMJ 2015; 351: h5876
    CrossrefPubMedSuche in Google Scholar
  • 27 Pandey AK, Xu K, Zhang L. et al. Lower versus standard INR targets in atrial fibrillation: a systematic review and meta-analysis of randomized controlled trials. Thromb Haemost 2020; 120 (03) 484-494
    Thieme ConnectPubMedSuche in Google Scholar