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CC BY 4.0 · Thromb Haemost
DOI: 10.1055/a-2524-5334
Stroke, Systemic or Venous Thromboembolism

Discontinuation of Anticoagulants and Occurrence of Bleeding and Thromboembolic Events in Vitamin K Antagonist Users with a Life-limiting Disease

Eva K. Kempers 
1   Department of Hematology, Erasmus MC, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands
,
Chantal Visser 
1   Department of Hematology, Erasmus MC, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands
,
Eric C. T. Geijteman
2   Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
,
Jamilla Goedegebuur
3   Department of Medicine - Thrombosis and Haemostasis, Leiden University Medical Center, Leiden, The Netherlands
4   Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands
,
Johanneke E. A. Portielje
5   Department of Medical Oncology, Leiden University Medical Center, Leiden, The Netherlands
,
Mette Søgaard
6   Department of Clinical Medicine, Danish Center for Health Services Research, Aalborg University, Aalborg University Hospital, Aalborg, Denmark
7   Center for General Practice, Aalborg University, Aalborg, Denmark
,
Anne Gulbech Ording
6   Department of Clinical Medicine, Danish Center for Health Services Research, Aalborg University, Aalborg University Hospital, Aalborg, Denmark
,
Carline van den Dries
8   Department of General Practice and Nursing Science, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
,
Denise Abbel
3   Department of Medicine - Thrombosis and Haemostasis, Leiden University Medical Center, Leiden, The Netherlands
9   Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands
10   LUMC Center for Medicine for Older People, LUMC, Leiden, The Netherlands
,
Geert-Jan Geersing
8   Department of General Practice and Nursing Science, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
,
Sarah J. Aldridge
11   Population Data Science, Faculty of Medicine, Health and Life Science, Swansea University, Swansea, United Kingdom
,
Kate J. Lifford
12   Division of Population Medicine, Wales Centre for Primary and Emergency Care Research (PRIME Centre Wales), Cardiff University, Cardiff, United Kingdom
,
Ashley Akbari
11   Population Data Science, Faculty of Medicine, Health and Life Science, Swansea University, Swansea, United Kingdom
,
Sjef J. C. M. van de Leur
13   Thrombosis Service, Isala Hospital Zwolle, Zwolle, The Netherlands
,
Melchior C. Nierman 
14   Department of Thrombosis and Anticoagulation, Atalmedial Medical Diagnostic Centers, Amsterdam, The Netherlands
,
Isabelle Mahé 
15   Department of Internal Medicine, Paris Cité University, Assistance Publique des Hôpitaux de Paris, Louis Mourier Hospital, INSERM UMR_S1140, Innovations Thérapeutiques en Hémostase, F-CRIN INNOVTE Network, Colombes, France
,
Simon P. Mooijaart
9   Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands
10   LUMC Center for Medicine for Older People, LUMC, Leiden, The Netherlands
,
Sebastian Szmit
16   Department of Cardio-Oncology, Centre of Postgraduate Medical Education, Warsaw, Poland
,
Michelle Edwards
17   Division of Population Medicine, Marie Curie Palliative Care Research Centre, Cardiff University, Cardiff, Wales, United Kingdom
,
Simon I. R. Noble
17   Division of Population Medicine, Marie Curie Palliative Care Research Centre, Cardiff University, Cardiff, Wales, United Kingdom
,
Frederikus A. Klok 
3   Department of Medicine - Thrombosis and Haemostasis, Leiden University Medical Center, Leiden, The Netherlands
,
Qingui Chen
4   Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands
,
Suzanne C. Cannegieter
3   Department of Medicine - Thrombosis and Haemostasis, Leiden University Medical Center, Leiden, The Netherlands
4   Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands
,
Marieke J. H. A. Kruip 
1   Department of Hematology, Erasmus MC, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands
,
SERENITY consortium› Author Affiliations
Funding This project has received funding from the European Union's Horizon Europe research and innovation action under grant agreement No. 101057292. Additionally, United Kingdom Research and Innovation (UKRI) has provided funding under the United Kingdom government's Horizon Europe funding guarantee (grant agreement No. 10039823 for Cardiff University and 10038000 for Hull York Medical School).
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Abstract

Background

Data on risks and benefits of long-term anticoagulants in patients with a life-limiting disease are limited. This cohort study aims to describe (dis)continuation of anticoagulants and incidences of bleeding and thromboembolic events in vitamin K antagonist (VKA) users with a life-limiting disease.

Methods

Data from five Dutch anticoagulation clinics were linked to data from Statistics Netherlands and the Netherlands Cancer registry. Prevalent VKA users diagnosed with a pre-specified life-limiting disease between January 1, 2013 and December 31, 2019 were included and followed until December 31, 2019. Bleeding and thromboembolic events were identified by hospitalization data. Cumulative incidences of anticoagulant discontinuation, accounting for death as competing risk, and event rates for both anticoagulant exposed and unexposed person-years (PYs) were determined.

Results

Among 18,145 VKA users (median age 81 years [IQR: 74–86], 49% females, median survival time 2.03 years [95%CI: 1.97–2.10]), the most common life-limiting diseases were heart disease (60.0%), hip fracture (18.1%), and cancer (13.5%). One year after diagnosis, the cumulative incidence of anticoagulant discontinuation was 14.0% (95%CI: 13.5–14.6). Over 80% of patients continued anticoagulant therapy until the last month before death, with median 14 days between discontinuation and death. Event rates per 100 PYs (95%CI) were comparable during anticoagulant use and after discontinuation for bleeding 2.6 (2.4–2.8) versus 2.1 (1.5–2.8), venous thromboembolism 0.2 (0.1–0.2) versus 0.4 (0.2–0.7), and arterial thromboembolism 3.1 (2.9–3.3) versus 3.3 (2.6–4.2).

Conclusion

Most VKA users with a life-limiting disease continued anticoagulant treatment during their last phase of life, with similar rates of bleeding and thromboembolic events during use and after discontinuation.

Keywords

anticoagulants - deprescriptions - thromboembolism - hemorrhage - advance care planning

Ethical Approval Statement

The study received approval from the Science Committee of the Department of Clinical Epidemiology at Leiden University Medical Center with a waiver for participant consent due to the use of pre-existing, de-identified data (#A0178). This study was performed on behalf of the SERENITY consortium.[25]


Data Availability Statement

This study used non-public microdata from Statistics Netherlands, the Federation of Dutch Anticoagulation Clinics, and the Netherlands Cancer Registry provided by the Netherlands Comprehensive Cancer Organization. These data cannot be shared directly by the authors. Under certain conditions, these data are accessible for statistical and scientific research. For additional information contact: microdata@cbs.nl, fnt@fnt.nl and/or gegevensaanvraag@iknl.nl.


Authors' Contribution

E.K.K., C.V., E.C.T.G., J.G., Q.C., M.J.H.A.K., and S.C.C. designed the study. E.K.K. and C.V. had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. E.K.K. and C.V. performed all data analyses. E.K.K. drafted the initial version of the manuscript. C.V., E.C.T.G., J.G., J.E.A.P., M.S., A.G.O., C.D., D.A., G.G., S.JA., K.J.L., A.A., S.J.C.M.L., M.C.N., I.M., S.P.M., S.S., M.E., S.I.R.N., F.A.K., Q.C., S.C.C., and M.J.H.A.K. contributed to the interpretation of the data and critically revised the manuscript. All authors approved the final version of the manuscript.


Supplementary Material



Publication History

Received: 09 October 2024

Accepted: 09 January 2025

Accepted Manuscript online:
24 January 2025

Article published online:
04 April 2025

© 2025. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

Georg Thieme Verlag KG
Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany

 

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