Purpose: The long-term consequences of recurrent venous thromboembolism (VTE) and post-thrombotic syndrome, clinical profiles of traditional and novel antithrombotic agents used to treat VTE, current treatment recommendations for acute symptomatic VTE, clinical experience with newer antithrombotic agents for acute treatment and extended secondary prevention of VTE, and an emerging VTE treatment paradigm are discussed.
Summary: Novel antithrombotic agents, with more specific activity on the coagulation cascade, more predictable pharmacodynamics and pharmacokinetics, simpler dosing regimens, and few or no laboratory monitoring requirements, have been developed to overcome limitations associated with some of the nonspecific traditional anticoagulants. Unfractionated heparin (UFH) and low molecular weight heparin (LMWH) are currently the recommended options for initial anticoagulation in patients with acute VTE. Warfarin is the most commonly used agent for chronic anticoagulation. Emerging evidence now also supports the role of factor-Xa inhibitors and oral direct thrombin inhibitors in the acute treatment and extended secondary prevention of VTE. In recent clinical trials, fondaparinux (a synthetic factor-Xa inhibitor) was comparable in efficacy and safety to unfractionated heparin for the treatment of acute symptomatic PE and to the LMWH enoxaparin for treating acute DVT. Ximelagatran, an oral direct thrombin inhibitor, was comparable in safety and efficacy to enoxaparin plus warfarin for treatment of acute VTE (DVT with or without PE). In addition, ximelagatran has been demonstrated to be superior to placebo for the extended secondary prevention of VTE, when continued for an additional 18 months beyond an initial six months of therapy. The benefits of extended anticoagulation for secondary VTE prevention have also been recently demonstrated with both low (INR 1.5-2.0) and regular intensity (INR 2.0-3.0) warfarin therapy.
Conclusion: A new paradigm for treating VTE is evolving based on the results of recent research to incorporate the use of emerging antithrombotic therapies in the acute treatment period and both traditional and novel agents in the chronic, extended-treatment period.