Duration of treatment with vitamin K antagonists in symptomatic venous thromboembolism (Cochrane Review)

A substantive amendment to this systematic review was last made on 12 January 2000. Cochrane reviews are regularly checked and updated if necessary.

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 - 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 reviewers sought publications through computerized searches of MEDLINE and EMBASE, and by hand-searching relevant journals, using the search strategy described by the Cochrane Review Group on Peripheral Vascular Diseases. They also contacted colleagues.

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: Six studies with a total of 2503 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 [0.12 - 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 1.28; 95% CI [0.91 - 1.80]). In addition, a substantial increase in bleeding complications was found during the entire period after randomization (OR 2.61; 95% CI [1.44 - 4.71]).

Reviewers' 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.

Citation: Hutten BA, Prins MH. Duration of treatment with vitamin K antagonists in symptomatic venous thromboembolism (Cochrane Review). In: The Cochrane Library, Issue 3, 2003. Oxford: Update Software.

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This is an abstract of a regularly updated, systematic review prepared and maintained by the Cochrane Collaboration. The full text of the review is available in The Cochrane Library (ISSN 1464-780X).

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