New treatments for venous thromboembolic disease

Following the landmark study by Barritt and Jordan in 1960, in which patients with venous thromboembolism (VTE) were randomized to no treatment or a combination of heparin and warfarin, antithrombotic therapy for this disease became widely accepted. This study was stopped prematurely because half of the non-treated patients had recurrent pulmonary embolism (PE), or died. It was subsequently found that after a VTE, patients given warfarin alone had a 3-4-fold higher incidence of recurrent VTE than patients given both heparin and warfarin. Since the 1990s, standard therapy for VTE has comprised an initial 5-7 day course of parenteral anticoagulant plus warfarin continued for at least 3 months. Recently, several orally active small molecules have been evaluated in the treatment of VTE, including a direct thrombin inhibitor and direct Factor Xa inhibitors. Other novel oral agents are also in development for VTE treatment. Although the DTI ximelagatran, the first oral agent to be introduced since warfarin was withdrawn from the market in Europe because of hepatotoxicity, evidence from clinical trial evaluating other single target-specific oral agents in the treatment of VTE is encouraging. It is therefore likely that use of warfarin in the treatment and secondary prevention of VTE will decrease should these novel oral agents be introduced for these indications. Additionally, there will be less distinction between initial and long-term therapy, and a great majority of patients will be treated on an outpatient basis for prolonged periods of time. Recently these expectations were fulfilled by the results of two Phase III studies in patients with VTE. The Recover I study indicated that Dabigatran (150mg b.d.) following an initial course of LMWH was non-inferior to the standard treatment of LMWH plus warfarin, with also a similar safety profile. The Einstein DVT study revealed that Rivaroxaban as a single agent can safely replace the standard treatment in patients with DVT. Taken together these studies and a few others that have or are about to be completed will indeed introduce a paradigm shift in the way patients with VTE will be treated. (C) 2011 Elsevier Masson SAS. All rights reserved.