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

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 durati ons of anticoagulation, identified in 1999 by a computerized search of the Cochrane Controlled Trial Register, Medline and Embase, completed by an ext ensive review of the references of pertinent articles. Setting and subjects. The meta-analysis was performed on literature data. S even published controlled trials were included. Relative risks with 95% con fidence intervals were computed using the relative risk logarithm method. S tatistical 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 dur ation 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 differe nt 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 recu rrence = 0.48, 95% CI: 0.34-0.68, P < 0.001). The tendency was similar, alt hough not reaching statistical significance, for the 'temporary risk factor s' 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 al lows a significant reduction in the incidence of recurrences without increa sing the incidence of bleeding events.