Evaluation of Once Weekly Subcutaneous Idraparinux Versus Standard Therapy with Heparin and Vitamin K Antagonists in the Treatment of Deep-Vein Thrombosis or Pulmonary Embolism - The Van Gogh Investigators.

Background

Venous thromboembolism is treated with heparins, followed by a vitamin K antagonist. It would be desirable to replace this complex approach with one simple anticoagulant regimen.

Methods

We conducted two randomized, open-label trials involving 2904 patients with deep-vein thrombosis and 2215 patients with pulmonary embolism to compare efficacy and safety of idraparinux alone versus standard therapy, and document non-inferiority for efficacy. Patients received either idraparinux (2.5 mg once-weekly, subcutaneously), or low-molecular-weight heparin/unfractionated heparin with adjusted-dose vitamin K antagonists, for three or six months. The primary efficacy outcome was the three-month incidence of symptomatic recurrent venous thromboembolism (nonfatal or fatal).

Results

In the deep-vein thrombosis study the incidence of recurrence at day 92 was 2.9 percent with idraparinux and 3.0 percent in controls (odds ratio 0.98, 95 percent confidence interval 0.63 to 1.50), satisfying the pre-specified non-inferiority requirement. The six-month hazard ratio was 1.01. The incidence of clinically relevant bleeding at day 92 was 4.5 percent and 7.0 percent , respectively (P<0.01). By six months bleeding rates were similar. In the pulmonary embolism study the incidence of recurrence at day 92 was 3.4 percent with idraparinux and 1.6 percent in controls (odds ratio 2.14, 95 percent confidence interval 1.21 to 3.78), excluding non-inferiority.

Conclusion

In patients with deep-vein thrombosis, once-weekly subcutaneous idraparinux for three or six months had similar efficacy and safety as heparins and vitamin K antagonists, while, in pulmonary embolism, this regimen was less efficacious than standard anticoagulant therapy which had an unexpectedly low recurrence rate.