Duration of treatment with vitamin K antagonists in symptomatic venous thromboembolism.
BACKGROUND
Currently the most frequently used secondary treatment for patients with venous thromboembolism are 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.


OBJECTIVE
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.


METHODS
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.


METHODS
Randomized controlled clinical trials comparing different durations of treatment with vitamin K antagonists in patients with symptomatic venous thromboembolism.


METHODS
Two reviewers extracted the data and assessed the quality of the trials independently.


RESULTS
Four studies with a total of exactly 1500 patients were included. A consistent reduction for the risk of recurrent events was observed during prolonged treatment with vitamin K antagonists (OR 0.15; 95% CI [0.10 - 0.23]) 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 1.11; 95% CI [0.71 - 1.75]). In addition, a substantial increase in bleeding complications was found during the entire period after randomization (OR 7.75; 95% CI [1.08 - 55.57]).


CONCLUSIONS
In conclusion this meta-analysis shows that treatment with vitamin K antagonists reduces the risk of recurrent venous thromboembolism 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 efficiency of vitamin K antagonist administration decreases over time since the index event.
Hutten
B A
BA
Academic Medical Center, Clinical Epidemiology & Biostatistics, J. 2-221, PO Box 22700, 1100 DE Amsterdam, Netherlands.
Prins
M H
MH
D000925:Anticoagulants / Q000008:administration & dosage*; D004334:Drug Administration Schedule; D006801:Humans; D011655:Pulmonary Embolism / Q000188:drug therapy*; D016032:Randomized Controlled Trials as Topic; D013997:Time Factors; D020246:Venous Thrombosis / Q000188:drug therapy*; D014812:Vitamin K / Q000037:antagonists & inhibitors*
D000925:Anticoagulants; D014812:Vitamin K