Duration of treatment with vitamin K antagonists in symptomatic venous thromboembolism

Background Currently, the most frequently used secondary treatment for patients with venous thromboembolism is vitamin K antagonists targeted at an INR of 2.5 (range 2.0 to 3.0). However, based on the continuing risk of bleeding and uncertainty regarding the risk of recurrent venous thromboembolism, there is discussion on the proper duration of treatment with vitamin K antagonists for these patients. Recently, several studies were published in which the risk and benefits of different durations of oral anticoagulants were compared in patients with venous thromboembolism. Objectives The objective of this review was to evaluate efficacy and safety of different durations of treatment with vitamin K antagonists in patients with symptomatic venous thromboembolism. Search strategy The Cochrane Peripheral Vascular Diseases Group searched their Specialised Register and the Cochrane Central Register of Controlled Trials (CENTRAL) in T h e Cochrane Library Issue 3, 2005). The Specialised Register is constructed from electronic searches of MEDLINE (from inception to October 2005) and EMBASE (inception to October 2005) and through handsearching relevant journals. In addition, we also contacted colleagues for details of trials. The last searches were carried out on 11 October 2005. Selection criteria Randomized controlled clinical trials comparing different durations of treatment with vitamin K antagonists in patients with symptomatic venous thromboembolism. Data collection and analysis Two reviewers (BH and MP) extracted the data and assessed the quality of the trials independently. Main results Eight studies with a total of 2994 patients were included. A consistent reduction in the risk of recurrent events was observed during prolonged treatment with vitamin K antagonists (OR 0.18; 95% CI 0.13 to 0.26) independent of the period elapsed since the index thrombotic event. A 'rebound' phenomenon, i.e. an excess of recurrences shortly after cessation of the prolonged treatment was not observed (OR 1.24; 95% CI 0.91 to 1.69). In addition, a substantial increase in bleeding complications was found during the entire period after randomization (OR 2.62; 95% CI 1.48 to 4.61). Authors' conclusions In conclusion, this meta-analysis shows that treatment with vitamin K antagonists reduces the risk of recurrent venous thromboembolism for as long as it is used. However, the absolute risk of recurrent venous thromboembolism declines over time, while the risk for major bleeding remains. Thus, the efficacy of vitamin K antagonist administration decreases over time since the index event.