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Meta-Analysis
. 2011 May 24:342:d3036.
doi: 10.1136/bmj.d3036.

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

Florent Boutitie  1 , Laurent Pinede, Sam Schulman, Giancarlo Agnelli, Gary Raskob, Jim Julian, Jack Hirsh, Clive Kearon
Affiliations
Meta-Analysis

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

Florent Boutitie et al. BMJ. .

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.

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Conflict of interest statement

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.

Figures

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Fig 1 Cumulative probability (top) and rate (bottom) of recurrent venous thromboembolism (VTE) after stopping treatment according to initial length of treatment (adjusted for age, sex, study, location of initial VTE, and presence of temporary risk factor. Rate of recurrent VTE calculated for 0-0.5, 0.5-1, 1-2, 2-4, 4-8, 8-12, 12-18, and 18-24 month intervals of follow-up
None
Fig 2 Cumulative probability (top) and rate (bottom) of recurrent venous thromboembolism (VTE) after stopping treatment according to whether VTE was pulmonary embolism, proximal deep vein thrombosis, or isolated distal deep vein thrombosis (adjusted for age, sex, study, length of treatment before stopping anticoagulant, and presence of temporary risk factor). Rate of recurrent VTE calculated for 0-0.5, 0.5-1, 1-2, 2-4, 4-8, 8-12, 12-18, and 18-24 month intervals of follow-up
None
Fig 3 Cumulative probability (top) and rate (bottom) of recurrent venous thromboembolism (VTE) after stopping treatment according to whether VTE was provoked by a temporary risk factor or was unprovoked (adjusted for age, sex, study, length of treatment before stopping anticoagulant, and location of initial VTE). Rate of recurrent VTE calculated for 0-0.5, 0.5-1, 1-2, 2-4, 4-8, 8-12, 12-18, and 18-24 month intervals of follow-up
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