Influence of preceding length of anticoagulant treatment and initial presentation of venous thromboembolism on risk of recurrence after stopping treatment: analysis of individual participants’ data from seven trials
BMJ 2011; 342 doi: https://doi.org/10.1136/bmj.d3036 (Published 24 May 2011) Cite this as: BMJ 2011;342:d3036
- Florent Boutitie, statistical investigator1,
- Laurent Pinede, investigator2,
- Sam Schulman, professor34,
- Giancarlo Agnelli, professor5,
- Gary Raskob, professor6,
- Jim Julian, statistical investigator7,
- Jack Hirsh, professor emeritus4,
- Clive Kearon, professor4
- 1Hospices Civils de Lyon, Service de Biostatistique, UMR 5558, CHU de Lyon, France
- 2Internal Medicine Department, Infirmerie Protestante, Lyon, France
- 3Haematology, Karolinska Hospital, Stockholm, Sweden
- 4Department of Medicine, McMaster University and Henderson Research Centre, Hamilton, ON, Canada
- 5Medicina Interna e Cardiovascolare—Stroke Unit, Università di Perugia, Perugia, Italy
- 6College of Public Health, University of Oklahoma, Health Sciences Center, Oklahoma City, OK, USA
- 7Department of Oncology, McMaster University and Henderson Research Centre, Hamilton, ON, Canada
- Correspondence to: C Kearon, Hamilton Health Sciences, Henderson Division, 711 Concession Street, Hamilton, ON, Canada L8V 1C3 kearonc{at}mcmaster.ca
- Accepted 30 March 2011
Abstract
Objective To determine how length of anticoagulation and clinical presentation of venous thromboembolism influence the risk of recurrence after anticoagulant treatment is stopped and to identify the shortest length of anticoagulation that reduces the risk of recurrence to its lowest level.
Design Pooled analysis of individual participants’ data from seven randomised trials.
Setting Outpatient anticoagulant clinics in academic centres.
Population 2925 men or women with a first venous thromboembolism who did not have cancer and received different durations of anticoagulant treatment.
Main outcome measure First recurrent venous thromboembolism after stopping anticoagulant treatment during up to 24 months of follow-up.
Results Recurrence was lower after isolated distal deep vein thrombosis than after proximal deep vein thrombosis (hazard ratio 0.49, 95% confidence interval 0.34 to 0.71), similar after pulmonary embolism and proximal deep vein thrombosis (1.19, 0.87 to 1.63), and lower after thrombosis provoked by a temporary risk factor than after unprovoked thrombosis (0.55, 0.41 to 0.74). Recurrence was higher if anticoagulation was stopped at 1.0 or 1.5 months compared with at 3 months or later (hazard ratio 1.52, 1.14 to 2.02) and similar if treatment was stopped at 3 months compared with at 6 months or later (1.19, 0.86 to 1.65). High rates of recurrence associated with shorter durations of anticoagulation were confined to the first 6 months after stopping treatment.
Conclusion Three months of treatment achieves a similar risk of recurrent venous thromboembolism after stopping anticoagulation to a longer course of treatment. Unprovoked proximal deep vein thrombosis and pulmonary embolism have a high risk of recurrence whenever treatment is stopped.
Footnotes
Contributors: FB participated in study design and obtaining peer reviewed funding, was primarily responsible for statistical analysis, drafted the manuscript, interpreted results, corresponded with the authors, and edited the manuscript. LP participated in study design and obtaining peer reviewed funding, interpreted results, provided additional unpublished data, and edited the manuscript. SS, GA, and JJ interpreted results, provided additional unpublished data, and edited the manuscript. GR interpreted the results and edited the manuscript. JH interpreted the results, provided administrative support, and edited the manuscript. CK drafted the manuscript, interpreted the results, corresponded with the authors, provided unpublished data, and edited the manuscript. All authors have had full access to all of the data and can take responsibility for the integrity of the data and the accuracy of the data analysis. FB and CK are the guarantors.
Funding: This study was supported by a grant from the French Ministry of Health (HCL-PHRC No 00.010). CK was supported by the Heart and Stroke Foundation of Ontario and by a Canadian Institutes of Health Research Team Grant in Venous Thromboembolism (FRN 79846). Sponsors of the analysis had no role in study design; the collection, analysis, and interpretation of data; or writing, review, or approval of the manuscript. The authors are independent of the sponsors.
Competing interests: All authors have completed the Unified Competing Interest form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: support from the French Ministry of Health; support for CK from the Heart and Stroke Foundation of Ontario and the Canadian Institutes of Health; no other relationships or activities that could appear to have influenced the submitted work.
Ethical approval: The original studies were approved by local research ethics committees; additional ethics approval was not needed for this analysis.
Data sharing: Access to the database is not yet widely available. The authors, who are the steering committee for this project, would be pleased to receive requests for access to the database. Such requests should outline study objectives and planned analyses and be accompanied by a study protocol.
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