Duration of treatment with vitamin K antagonists in symptomatic venous thromboembolism

Cochrane Database Syst Rev. 2014 Aug 5;2014(8):CD001367. doi: 10.1002/14651858.CD001367.pub3.


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.

Objectives: To evaluate the efficacy and safety of different durations of treatment with vitamin K antagonists in patients with symptomatic venous thromboembolism.

Search 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.

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: Three review authors (SM, MP, and BH) extracted the data and assessed the quality of the trials independently.

Main 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).

Authors' 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.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Anticoagulants / administration & dosage*
  • Anticoagulants / adverse effects
  • Drug Administration Schedule
  • Hemorrhage / chemically induced
  • Humans
  • International Normalized Ratio
  • Randomized Controlled Trials as Topic
  • Secondary Prevention
  • Thromboembolism / prevention & control*
  • Time Factors
  • Venous Thrombosis / prevention & control*
  • Vitamin K / antagonists & inhibitors*


  • Anticoagulants
  • Vitamin K