title: Duration of treatment with vitamin K antagonists in symptomatic venous thromboembolism.
abstract: BACKGROUND
  Currently, the most frequently used secondary treatment for patients with venous thromboembolism (VTE) consists of vitamin K antagonists (VKA) targeted at an international normalized ratio (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 VTE, discussion on the proper duration of treatment with VKA for these patients is ongoing. Several studies have compared the risks and benefits of different durations of VKA in patients with VTE. This is the third update of a review first published in 2000.
  
  
  OBJECTIVE
  To evaluate the efficacy and safety of different durations of treatment with vitamin K antagonists in patients with symptomatic venous thromboembolism.
  
  
  METHODS
  For this update, the Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched October 2013) and the Cochrane Central Register of Controlled Trials (CENTRAL) 2013, Issue 9.
  
  
  METHODS
  Randomized controlled clinical trials comparing different durations of treatment with vitamin K antagonists in patients with symptomatic venous thromboembolism.
  
  
  METHODS
  Three review authors (SM, MP, and BH) extracted the data and assessed the quality of the trials independently.
  
  
  RESULTS
  Eleven studies with a total of 3716 participants were included. A consistent and strong reduction in the risk of recurrent venous thromboembolic events was observed during prolonged treatment with VKA (risk ratio (RR) 0.20, 95% confidence interval (CI) 0.11 to 0.38) independent of the period elapsed since the index thrombotic event. A statistically significant "rebound" phenomenon (ie, an excess of recurrences shortly after cessation of prolonged treatment) was not found (RR 1.28, 95% CI 0.97 to 1.70). In addition, a substantial increase in bleeding complications was observed for patients receiving prolonged treatment during the entire period after randomization (RR 2.60, 95% CI 1.51 to 4.49). No reduction in mortality was noted during the entire study period (RR 0.89, 95% CI 0.66 to 1.21, P = 0.46).
  
  
  CONCLUSIONS
  In conclusion, this review shows that treatment with VKA strongly reduces the risk of recurrent VTE for as long as they are used. However, the absolute risk of recurrent VTE declines over time, although the risk for major bleeding remains. Thus, the efficacy of VKA administration decreases over time since the index event.
authors.affiliation: Department of Vascular Medicine, Academic Medical Center, Meibergdreef 9, Amsterdam, Netherlands, 1105AZ.
authors.forename: Saskia
authors.initials: S
authors.lastname: Middeldorp
authors.forename: Martin H
authors.initials: MH
authors.lastname: Prins
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Hutten
mesh_terms: D000925:Anticoagulants / Q000008:administration & dosage* / Q000009:adverse effects; D004334:Drug Administration Schedule; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D019934:International Normalized Ratio; D016032:Randomized Controlled Trials as Topic; D055502:Secondary Prevention; D013923:Thromboembolism / Q000517:prevention & control*; D013997:Time Factors; D020246:Venous Thrombosis / Q000517:prevention & control*; D014812:Vitamin K / Q000037:antagonists & inhibitors*
chemical_list: D000925:Anticoagulants; D014812:Vitamin K
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