Vitamin K antagonists or low-molecular-weight heparin for the long term treatment of symptomatic venous thromboembolism

van der Heijden JF, Hutten BA, Büller HR, Prins MH

Published Online:

March 16, 2011

Not enough evidence that low-molecular-weight heparin is more effective than vitamin K antagonists for the treatment of blood clots in veins (venous thromboembolism). Blood clots sometimes cause blockages in veins after surgery, bed rest, or spontaneously. These clots can be fatal, when they end up in the lungs. Vitamin K antagonists are effective in preventing renewed blood clot formation, by thinning the blood. Low-molecular-weight heparin is a drug that also thins the blood but is expensive. Pregnant women or people with an increased risk of major bleeding cannot take vitamin K antagonists. The review of trials found insufficient evidence of differences in the safety and effectiveness of low-molecular-weight heparin compared to vitamin K antagonists. More research is needed into the long-term treatment of blood clots in veins.

Abstract (click to read)

Background:

People with venous thromboembolism (VTE) are generally treated for five days with intravenous unfractionated heparin or subcutaneous low-molecular-weight heparin (LMWH) followed by three months of vitamin K antagonists treatment. Treatment with vitamin K antagonists requires regular laboratory measurements and some patients have contraindications for treatment.

Objectives:

To evaluate the efficacy and safety of long-term treatment of VTE with low-molecular-weight heparins compared to vitamin K antagonists.

Search strategy:

Searches of MEDLINE, EMBASE and ISI Web of Science, the Specialised Register of the Cochrane Peripheral Vascular Diseases Group and the Cochrane Controlled Trials Register were made and relevant journals were hand-searched. Additional trials were sought through communication with colleagues and pharmaceutical companies.

Selection criteria:

Two authors evaluated studies independently for methodological quality.

Data collection and analysis:

Two authors extracted data independently.

Primary analysis concerned all trial participants during the period of randomized treatment. Separate analyses were performed for category I and category II studies; i.e. studies using similar treatments initially in both study arms, and those that did not; and the different periods of follow-up.

Main results:

All seven studies fulfilling our criteria combined, a statistically non-significant reduction in the risk of recurrent VTE favoring LMWH treatment (OR 0.70; 95% CI [0.42 to 1.16]) was found. Analysis of pooled data for category I studies showed a non-significant reduction in the risk of recurrent VTE favoring LMWH treatment (OR 0.75; 95% CI [0.40 to 1.39]). Omitting a potentially-confounded study, a statistically non-significant reduction in the risk of recurrent VTE favoring vitamin K antagonist treatment remained (OR 1.95; 95% CI [0.74 to 5.19]).

All studies combined, the difference in bleeding significantly favored treatment with LMWH (OR 0.38; 95% CI [0.15 to 0.94]), however, considering only category I studies a non-significant trend favoring LMWH remained (OR 0.80; 95% CI [0.21 to 3.00]). No difference was observed in mortality (OR 1.13; 95% CI [0.47 to 2.69]).

Authors' conclusions:

Low-molecular-weight heparins are possibly as effective as vitamin K antagonists in preventing symptomatic VTE after an episode of symptomatic deep venous thrombosis, but are much more expensive. Treatment with LMWH is significantly safer than treatment with vitamin K antagonists and is possibly a safe alternative in some patients; especially those in geographically inaccessible places, reluctant to visit the thrombosis service regularly, or with contraindications to vitamin K antagonists. However, treatment with vitamin K antagonists remains the treatment of choice for the majority of patients.

This record should be cited as:

van der Heijden JF, Hutten BA, Büller HR, Prins MH. Vitamin K antagonists or low-molecular-weight heparin for the long term treatment of symptomatic venous thromboembolism. Cochrane Database of Systematic Reviews 2000, Issue 4. Art. No.: CD002001. DOI: 10.1002/14651858.CD002001

Assessed as up to date:

May 14, 2003

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Primary Review Group:

Peripheral Vascular Diseases Group

Health topics:

Heart & circulation > Deep vein thrombosis > Treatment

Cochrane Summaries^beta

Independent high-quality evidence for health care decision making

Vitamin K antagonists or low-molecular-weight heparin for the long term treatment of symptomatic venous thromboembolism

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