Comparison of long versus short duration of anticoagulant therapy after a first episode of venous thromboembolism: a meta-analysis of randomized, controlled trials


Dr Laurent Pinède, Department of Internal Medicine, Edouard Herriot Hospital, 69437 Lyons Cedex 03, France (fax: 33-4 72 11 75 67; e-mail:


Abstract. Pinede L, Duhaut P, Cucherat M, Ninet J, Pasquier J, Boissel JP (Hôpital Edouard Herriot and Unité de Pharmacologie Clinique, Lyon, France). J Intern Med 2000; 247: 553–562.

Objective. To assess the length of oral anticoagulant therapy (short versus long duration) after a first episode of venous thromboembolism (VTE).

Design. Meta-analysis of randomized controlled trials, comparing two durations of anticoagulation, identified in 1999 by a computerized search of the Cochrane Controlled Trial Register, Medline and Embase, completed by an extensive review of the references of pertinent articles.

Setting and subjects. The meta-analysis was performed on literature data. Seven published controlled trials were included. Relative risks with 95% confidence intervals were computed using the relative risk logarithm method. Statistical significance was set up at 0.01 for the test of association.

Main outcome measures. Outcomes are major haemorrhage and recurrence after a 12-month follow-up.

Results. For the recurrence end-point (sample size of 2304 patients), a duration treatment of 12–24 weeks seems preferable to a 3–6 week regimen, with a relative risk (RR) of 0.60 (95% CI: 0.45–0.79, P < 0.001). For the major haemorrhage end-point (1823 patients), the RR is not significantly different from 1 (RR = 1.43, 95% CI: 0.51–4.01, P = 0.5). The results were similar for the subgroup ‘permanent risk factors’ or ‘idiopathic VTE’ (RR for recurrence = 0.48, 95% CI: 0.34–0.68, P < 0.001). The tendency was similar, although not reaching statistical significance, for the ‘temporary risk factors’ subgroup (RR for recurrence = 0.34, 95% CI: 0.13–0.93, P = 0.035).

Conclusions. After a first episode of VTE, a long-term treatment regimen allows a significant reduction in the incidence of recurrences without increasing the incidence of bleeding events.