Idraparinux versus standard therapy for venous thromboembolic disease.
Résumé
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].).