Is idraparinux safe and effective for the treatment of acute venous thromboembolism?
Once-weekly subcutaneous idraparinux was as safe and effective as standard treatment with heparin and vitamin K antagonists for acute deep venous thrombosis (DVT), but the rates of recurrent thromboembolism and mortality were increased in patients with pulmonary embolism (PE). (LOE = 1b)
The van Gogh Investigators, Buller HR, Cohen AT, et al. Idraparinux versus standard therapy for venous thromboembolic disease. N Engl J Med 2007;357(11):1094-1104. [PMID:17855670]
Randomized controlled trial (nonblinded)
Inpatient (any location) with outpatient follow-up
Idraparinux is a factor X inhibitor with a long half life that allows once-weekly administration of a fixed subcutaneous dose. This paper reports the results of 2 separate noninferiority trials comparing weekly subcutaneous idraparinux versus standard therapy (unfractionated or low-molecular-weight heparin and vitamin K antagonist). The first trial included patients with acute DVT and the second trial studied patients with acute PE. Randomization was stratified for planned duration of anticoagulation, either 3 months or 6 months, as determined by the treating physician on the basis of perceived risk of recurrence. These were open-label, industry-funded studies, with data gathered and maintained by the sponsor. Outcomes were classified and reviewed by masked adjudication and monitoring committees. The primary outcome was incidence of recurrent venous thromboembolism (VTE) at 3 months. Secondary outcomes included recurrence rates at 6 months (for patients receiving 6 months of treatment) and clinically relevant bleeding. All outcomes were analyzed by intention to treat, and follow-up was complete for more than 99% of patients.. In the DVT study, the authors enrolled 2904 patients (of 6054 screened), with 22% treated for 3 months. The PE study included 2215 patients (of 4628 eligible), of whom 9% were planned for 3 months of treatment. Patients were matched for baseline characteristics. In the DVT study, idraparinux was noninferior to standard therapy at 92 days (risk of recurrent VTE = 2.9% vs 3.0%) and at 183 days (risk of recurrent VTE = 3.7% in both groups). For the PE study, idraparinux increased rates of recurrent VTE compared with standard treatment at 92 days [3.4% vs 1.6%; number needed to treat to harm (NNTH) = 56; 95% CI, 32 - 211] and at 183 days (4.0% vs 2.0%; NNTH = 49; 28 - 175). Bleeding rates were reduced in the DVT patients treated with idraparinux at 92 days (4.5% vs 7.0%; number needed to treat = 40; 24 - 126), but not at 183 days (8.3% vs 8.1%). Bleeding was also reduced in the PE patients treated with idraparinux at 92 days and major bleeding was lower in the idraparinux group at 183 days. Mortality rates were higher in PE patients treated with idraparinux at both end points (at 92 days: NNTH = 44; 25 - 159; at 183 days: NNTH= 50; 25 - 3090).
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