Idraparinux versus standard therapy for venous thromboembolic disease.

Abstract

BACKGROUND:

Venous thromboembolism is treated with unfractionated heparin or low-molecular-weight heparin, followed by a vitamin K antagonist. We investigated the potential use of idraparinux, a long-acting inhibitor of activated factor X, as a substitute for standard therapy.

METHODS:

We conducted two randomized, open-label noninferiority trials involving 2904 patients with deep-vein thrombosis and 2215 patients with pulmonary embolism to compare the efficacy and safety of idraparinux versus standard therapy. Patients received either subcutaneous idraparinux (2.5 mg once weekly) or a heparin followed by an adjusted-dose vitamin K antagonist for either 3 or 6 months. The primary efficacy outcome was the 3-month incidence of symptomatic recurrent venous thromboembolism (nonfatal or fatal).

RESULTS:

In the study of patients with deep venous thrombosis, the incidence of recurrence at day 92 was 2.9% in the idraparinux group as compared with 3.0% in the standard-therapy group (odds ratio, 0.98; 95% confidence interval [CI], 0.63 to 1.50), a result that satisfied the prespecified noninferiority requirement. At 6 months, the hazard ratio for idraparinux was 1.01. The rates of clinically relevant bleeding at day 92 were 4.5% in the idraparinux group and 7.0% in the standard-therapy group (P=0.004). At 6 months, bleeding rates were similar. In the study of patients with pulmonary embolism, the incidence of recurrence at day 92 was 3.4% in the idraparinux group and 1.6% in the standard-therapy group (odds ratio, 2.14; 95% CI, 1.21 to 3.78), a finding that did not meet the noninferiority requirement.

CONCLUSIONS:

In patients with deep venous thrombosis, once-weekly subcutaneous idraparinux for 3 or 6 months had an efficacy similar to that of heparin plus a vitamin K antagonist. However, in patients with pulmonary embolism, idraparinux was less efficacious than standard therapy. (ClinicalTrials.gov numbers, NCT00067093 [ClinicalTrials.gov] and NCT00062803 [ClinicalTrials.gov].).

• Authors: van Gogh Investigators, Harry R Buller, Ander T Cohen, Bruce Davidson, Hervé Decousus, Alex S Gallus, Michael Gent, Gerard Pillion, Franco Piovella, Martin H Prins, Gary E Raskob
• Journal: The New England journal of medicine (N Engl J Med) Vol. 357 Issue 11 Pg. 1094-104 (Sep 13 2007) ISSN: 1533-4406 [Electronic] United States
• PMID: 17855670 (Publication Type: Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2007 Massachusetts Medical Society.

Chemical References

• Anticoagulants
• Oligosaccharides
• Vitamin K
• idraparinux
• Heparin

Topics

• Anticoagulants (adverse effects, therapeutic use)
• Female
• Follow-Up Studies
• Hemorrhage (chemically induced)
• Heparin (adverse effects, therapeutic use)
• Humans
• Incidence
• Male
• Middle Aged
• Oligosaccharides (adverse effects, therapeutic use)
• Pulmonary Embolism (drug therapy, mortality)
• Recurrence
• Treatment Outcome
• Venous Thrombosis (drug therapy, mortality)
• Vitamin K (antagonists & inhibitors)