Long-Term Risk of Major Bleeding after Discontinuing Anticoagulation for Unprovoked Venous Thromboembolism: A Systematic Review and Meta-analysis

Faizan Khan; Alvi Rahman; Tobias Tritschler; Marc Carrier; Clive Kearon; Jeffrey I. Weitz; Sam Schulman; Francis Couturaud; Cecilia Becattini; Giancarlo Agnelli; Timothy A. Brighton; Anthonie W. A. Lensing; Laurent Pinede; Sameer Parpia; Geert-Jan Geersing; Toshihiko Takada; Charlotte A. Bradbury; Giuseppe M. Andreozzi; Gualtiero Palareti; Paolo Prandoni; Harry R. Buller; Ranjeeta Mallick; Brian Hutton; Kednapa Thavorn; Gregoire Le Gal; Marc A. Rodger; Dean A. Fergusson

doi:10.1055/a-1690-8728

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 2022; 122(07): 1186-1197
DOI: 10.1055/a-1690-8728

Stroke, Systemic or Venous Thromboembolism

Long-Term Risk of Major Bleeding after Discontinuing Anticoagulation for Unprovoked Venous Thromboembolism: A Systematic Review and Meta-analysis

Faizan Khan

¹School of Epidemiology and Public Health, University of Ottawa, Ottawa, Canada

²Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Canada

,

Alvi Rahman

³Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Canada

,

Tobias Tritschler

⁴Department of General Internal Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland

,

Marc Carrier

¹School of Epidemiology and Public Health, University of Ottawa, Ottawa, Canada

²Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Canada

,

Clive Kearon

⁵The Thrombosis and Atherosclerosis Research Institute, Department of Medicine, McMaster University, Hamilton, Canada

,

Jeffrey I. Weitz

⁵The Thrombosis and Atherosclerosis Research Institute, Department of Medicine, McMaster University, Hamilton, Canada

,

Sam Schulman

⁵The Thrombosis and Atherosclerosis Research Institute, Department of Medicine, McMaster University, Hamilton, Canada

⁶Department of Obstetrics and Gynecology, The First I.M. Sechenov Moscow State Medical University, Moscow, Russia

,

Francis Couturaud

⁷Department of Internal Medicine and Chest Diseases, Brest University Hospital, Brest, France

,

Cecilia Becattini

⁸Internal and Cardiovascular Medicine, Stroke Unit, University of Perugia, Perugia, Italy

,

Giancarlo Agnelli

⁸Internal and Cardiovascular Medicine, Stroke Unit, University of Perugia, Perugia, Italy

,

Timothy A. Brighton

⁹Department of Haematology, Prince of Wales Hospital, Sydney, Australia

,

Anthonie W. A. Lensing

¹⁰Bayer AG, Wuppertal, Germany

,

Laurent Pinede

¹¹Department of Internal Medicine, Infirmerie Protestante, Caluire - Lyon, France

,

Sameer Parpia

¹²Departments of Oncology, and Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Ontario, Canada

,

Geert-Jan Geersing

¹³Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands

,

Toshihiko Takada

¹³Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands

,

Charlotte A. Bradbury

¹⁴School of Cellular and Molecular Medicine, University of Bristol, Bristol, United Kingdom

,

Giuseppe M. Andreozzi

¹⁵Angiology Care Unit, University of Padova, Padova, Italy

,

Gualtiero Palareti

¹⁶Arianna Foundation on Anticoagulation, Bologna, Italy

,

Paolo Prandoni

¹⁶Arianna Foundation on Anticoagulation, Bologna, Italy

,

Harry R. Buller

¹⁷Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands

,

Ranjeeta Mallick

²Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Canada

,

Brian Hutton

¹School of Epidemiology and Public Health, University of Ottawa, Ottawa, Canada

²Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Canada

,

Kednapa Thavorn

¹School of Epidemiology and Public Health, University of Ottawa, Ottawa, Canada

²Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Canada

,

Gregoire Le Gal

¹School of Epidemiology and Public Health, University of Ottawa, Ottawa, Canada

²Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Canada

,

Marc A. Rodger^*

²Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Canada

¹⁸Department of Medicine, McGill University, Montreal, Canada

,

Dean A. Fergusson

¹School of Epidemiology and Public Health, University of Ottawa, Ottawa, Canada

²Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Canada

¹School of Epidemiology and Public Health, University of Ottawa, Ottawa, Canada

› Institutsangaben

Abstract

Background The long-term risk of major bleeding after discontinuing anticoagulant therapy for a first unprovoked venous thromboembolism (VTE) is uncertain.

Objectives To determine the incidence of major bleeding up to 5 years after discontinuing anticoagulation for a first unprovoked VTE.

Methods We searched MEDLINE, EMBASE, and Cochrane CENTRAL (from inception to January 2021) to identify relevant randomized controlled trials (RCTs) and prospective cohort studies reporting major bleeding after discontinuing anticoagulation in patients with a first unprovoked or weakly provoked VTE who had completed (IMAGE_)3 months of initial treatment. Unpublished data on major bleeding events and person-years were obtained from authors of included studies to calculate study-level incidence rates. Random-effects meta-analysis was used to pool results across studies.

Results Of 1,123 records identified by the search, 20 studies (17 RCTs) and 8,740 patients were included in the analysis. During 13,011 person-years of follow-up after discontinuing anticoagulation, the pooled incidence of major bleeding (n = 41) and fatal bleeding (n = 7) per 100 person-years was 0.35 (95% confidence interval [CI]: 0.20–0.54) and 0.09 (95% CI: 0.05–0.15). The 5-year cumulative incidence of major bleeding was of 1.0% (95% CI: 0.4–2.4%). The case-fatality rate of major bleeding after discontinuing anticoagulation was 19.9% (95% CI: 10.6–31.1%).

Conclusion The risk of major bleeding once anticoagulants are discontinued in patients with a first unprovoked VTE is not zero. Estimates from this study can help clinicians counsel patients about the incremental risk of major bleeding with extended anticoagulation to guide decision making about treatment duration for unprovoked VTE.

Keywords

anticoagulation - major bleeding - prognosis - thrombosis - venous thromboembolism

Volltext

Referenzen

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