Long Acting Anticoagulant Effects of Idraparinux in Patients Treated for Prophylaxis of Recurrent Venous Thromboembolism.

Prophylaxis of recurrent venous thromboembolism (VTE) has been investigated in patients with acute VTE participating in the VanGogh DVT, PE and Extension studies for a minimum of 6 months. These patients were given a fixed dose of Idraparinux once a week subcutaneously without coagulation monitoring. The VanGogh DVT/PE studies randomized patients to Idraparinux versus INR-adjusted Warfarin. Patients were then able to follow on to the double-blind VanGogh Extension study comparing Idraparinux versus placebo. Determination of the anticoagulant effects may still be necessary for patients in acute clinical settings. After termination of the studies, the anticoagulant effects of Idraparinux were followed-up in 23 patients using Heptest coagulation method, anti-factor Xa inhibition method (aXa, chromogenic substrate S2222) and prothrombin induced clotting time (PiCT) assay. The study was accepted by the local ethics board and patients gave written informed consent. Serial blood samples were taken for up to 15 months after termination. The Heptest and PiCT methods were prolonged in all patients’ blood for 9 to 15 months after therapy termination. The chromogenic assay method showed factor-Xa inhibition for the same period of follow-up. The elimination half-life of Idraparinux was calculated at 60.5 ± 23.3 days using the Heptest method and at 55.1±15.4 days using the aXa-assay method. There were no differences noted in the half-life between patients participating in the DVT/PE and Extension study. The half-lives were independent from patients’ body weight and creatinine clearance. The complete pharmacokinetic analysis of the results will be presented. The unexpectedly long half-life may be explained by the lipophilicity of methylated Idraparinux. Overall, the data suggests a benefit from the prolonged antithrombotic effect of Idraparinux as well as an increased risk of hemorrhage after therapy termination, possibly explaining some of the van Gogh studies results.