Duration of Anticoagulation Therapy for Venous Thromboembolism

Abstract

Treatment of acute deep vein thrombosis and pulmonary embolism-often denominated together as venous thromboembolism (VTE)- consists of parenteral administration of heparin (usually low-molecular-weight heparin or alternatively unfractionated heparin or fondaparinux) overlapped and followed by oral vitamin K antagonists that are administered for a certain period (usually 3 to 12 months). Recommended or suggested durations differ according to guidelines. Practically, the clinical decision in an individual patient depends upon the estimated risks of VTE recurrence and treatment-induced bleeding. The risk of VTE recurrence is higher in idiopathic events (about 10% per year during the first two years and 3% per year thereafter) (odds ratio of 2.4, compared to secondary events); in male subjects (at least before the age of 60, with an odds ratio of 2-4); in patients with persistently elevated D-dimer level (odds ratio of 2.3, compared with normal level); and during the first two years after discontinuation of treatment. The annual risk of major bleeding on anticoagulant treatment vary largely in observational studies with figures of 2% to 29%, depending on the patient characteristics. The case-fatality rate is 8% (DVT), 12% (PE) for recurrent VTE, and about 10% for major bleed. These figures do not support long-term anticoagulant therapy, except in those patients exhibiting a very high risk of recurrence and/or a very low risk of bleeding. New therapeutic aspects might impact on the duration of anticoagulant therapy after a venous thromboembolic event. They include the possibility of pursuing anticoagulant treatment at a reduced INR after an initial period with an INR 2-3, and the advent of new, more specific and orally active anticoagulants. These features might modify the risk-benefit balance of extending anticoagulant therapy beyond the usual, limited duration.