Vitamin K antagonists or low-molecular-weight heparin for the long term treatment of symptomatic venous thromboembolism.
BACKGROUND
People with venous thromboembolism are generally treated for five days with intravenous unfractionated heparin or subcutaneous low-molecular-weight heparin 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.


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


METHODS
Searches of MEDLINE, EMBASE and ISI Web of Science, the Specialised Trials Register of the Cochrane Peripheral Vascular Disease 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.


METHODS
Two reviewers evaluated studies independently for methodological quality.


METHODS
Two reviewers 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.


RESULTS
All seven studies fulfilling our criteria combined, a statistically non-significant reduction in the risk of recurrent venous thromboembolism favoring low-molecular-weight heparin treatment (OR 0.70; 95% CI [0.42, 1.16]) was found. Analysis of pooled data for category I studies showed a non-significant reduction in the risk of recurrent venous thromboembolism favoring low-molecular-weight heparin treatment (OR 0.75; 95% CI [0.40, 1.39]). Omitting a potentially-confounded study, a statistically non-significant reduction in the risk of recurrent venous thromboembolism favoring vitamin K antagonist treatment remained (OR 1.95; 95% CI [0.74, 5.19]). All studies combined, the difference in bleeding significantly favored treatment with low-molecular-weight heparin (OR 0.38; 95% CI [0.15, 0.94]), however, considering only category I studies a non-significant trend favoring low-molecular-weight heparin remained (OR 0.80; 95% CI [0.21, 3.00]). No difference was observed in mortality (OR 1.13; 95% CI [0.47, 2.69]).


CONCLUSIONS
Low-molecular-weight heparins are possibly as effective as vitamin K antagonists in preventing symptomatic venous thromboembolism after an episode of symptomatic deep venous thrombosis, but are much more expensive. Treatment with low-molecular-weight heparin 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.
van der Heijden
J F
JF
Laboratory for Experimental Internal Medicine (room F4-121), Academic Medical Center, Meibergdreef 9, PO Box 22660, 1100 DD Amsterdam, Netherlands. j.f.vanderheijden@amc.uva.nl
Hutten
B A
BA
Büller
H R
HR
Prins
M H
MH
D000925:Anticoagulants / Q000627:therapeutic use*; D006495:Heparin, Low-Molecular-Weight / Q000627:therapeutic use*; D006801:Humans; D016017:Odds Ratio; D016032:Randomized Controlled Trials as Topic; D020246:Venous Thrombosis / Q000188:drug therapy*; D014812:Vitamin K / Q000037:antagonists & inhibitors*
D000925:Anticoagulants; D006495:Heparin, Low-Molecular-Weight; D014812:Vitamin K