Extended prophylaxis of venous thromboembolism with idraparinux

N Engl J Med. 2007 Sep 13;357(11):1105-12. doi: 10.1056/NEJMoa067703.

Abstract

Background: The extended use of vitamin K antagonists for prophylaxis against venous thromboembolism is often constrained by risk-benefit limitations and inconvenience. We evaluated the efficacy and safety of a 6-month extension of prophylaxis against recurrent venous thromboembolism with idraparinux in patients who had initially received 6 months of prophylaxis with an anticoagulant.

Methods: We randomly assigned patients who had completed 6 months of prophylaxis with idraparinux or a vitamin K antagonist and in whom extended anticoagulation was warranted to receive once-weekly injections of 2.5 mg of idraparinux or placebo for 6 months without monitoring. The primary efficacy and safety outcomes were recurrent venous thromboembolism and major bleeding.

Results: Of 1215 patients, 6 of 594 (1.0%) in the idraparinux group and 23 of 621 (3.7%) in the placebo group had recurrent venous thromboembolism (P=0.002). Major bleeding occurred in 11 patients (1.9%) in the idraparinux group and in none in the placebo group (P<0.001). Of these 11 episodes, 3 were fatal intracranial hemorrhages. As compared with patients whose initial treatment was a vitamin K antagonist, patients whose initial treatment was idraparinux who were assigned to 6 months in the placebo group had a lower incidence of recurrent thromboembolism (0.7% vs. 5.9%); patients who received 6 additional months of idraparinux therapy had a higher incidence of major bleeding (3.1% vs. 0.9%).

Conclusions: During a 6-month extension of thromboprophylaxis, idraparinux was effective in preventing recurrent thromboembolism but was associated with an increased risk of a major hemorrhage. (ClinicalTrials.gov number, NCT00071279 [ClinicalTrials.gov].).

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Anticoagulants / administration & dosage*
  • Anticoagulants / adverse effects
  • Anticoagulants / therapeutic use
  • Double-Blind Method
  • Drug Administration Schedule
  • Factor Xa Inhibitors
  • Female
  • Follow-Up Studies
  • Hemorrhage / chemically induced
  • Humans
  • Injections, Subcutaneous
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Oligosaccharides / administration & dosage*
  • Oligosaccharides / adverse effects
  • Oligosaccharides / therapeutic use
  • Pulmonary Embolism / drug therapy*
  • Pulmonary Embolism / mortality
  • Secondary Prevention
  • Treatment Outcome
  • Venous Thrombosis / drug therapy*
  • Venous Thrombosis / mortality
  • Vitamin K / antagonists & inhibitors

Substances

  • Anticoagulants
  • Factor Xa Inhibitors
  • Oligosaccharides
  • Vitamin K
  • idraparinux

Associated data

  • ClinicalTrials.gov/NCT00071279