Treatment of venous thromboembolism: challenging the unfractionated heparin standard

Venous thromboembolism (VTE) is a major public health problem leading to high morbidity and mortality in the United States. Since more then 50% of patients with VTE may have asymptomatic disease, the start of appropriate therapy often is delayed. Traditionally, intravenous unfractionated heparin (UFH) has been used to manage the acute phase of VTE. Although an effective agent, numerous limitations are associated with the use of UFH therapy, such as the need for careful monitoring and frequent dosing adjustments. In addition, the assay used to monitor UFH--the activated partial thromboplastin time (aPTT)--does not correlate reliably with plasma heparin levels or antithrombotic activity. In the early 1990s, the low-molecular-weight heparins (LMWHs) emerged as alternative anticoagulants to UFH and began to successfully challenge the UFH standard for treatment of VTE. Clinical evidence has consistently demonstrated that LMWHs given subcutaneously are at least as safe and as effective, if not better, than intravenous UFH. This anticoagulant class has a much more predictable dose-response relationship, requires little or no monitoring, and provides cost-saving opportunities for outpatient management of VTE. The LMWHs are now considered the treatment of choice for many patients with VTE and are largely replacing UFH for this indication. In the last decade, additional agents, such as direct thrombin inhibitors and factor Xa inhibitors, have emerged as potential future alternatives for treatment of VTE. As clinical data regarding these new agents for treatment of VTE continue to evolve, their role in clinical practice will be elucidated.