Current roles and future possibilities for low-molecular-weight heparins in unstable angina

Intravenous unfractionated heparin (UFH) is associated with several limitations, including short duration of action, poor bioavailability, unpredictable anticoagulant response, a risk of heparin-induced thrombocytopenia (HIT), and disease reactivation following early discontinuation. Because of these limitations, there is interest in the development of newer antithrombotic strategies. Low-molecular-weight heparins (LMWHs) offer potential benefits over standard heparin and allow the opportunity for subcutaneous self-administration for longer periods. In the acute phase of unstable angina, LMWHs have been shown to be superior to placebo and at least as effective as UFH in reducing death, myocardial infarction and recurrent angina. Trials of longer-term therapy with LMWHs are in progress. Although animal studies have suggested that LMWHs, by reducing neo-intimal proliferation, may prevent restenosis following coronary angioplasty, clinical trials have been disappointing. However, an initial study with the LMWH enoxaparin (Lovenox/Clexane) and ticlopidine after elective stenting (ENTICES) showed a reduction in stent thrombosis and ischaemic events. This has led to a further trial of antiplatelet therapy versus Lovenox plus antiplatelet therapy for patients with an increased risk of stent thrombosis (ATLAST). Further studies are assessing the role of diffusion and pressure-driven and mechanical devices to deliver high and sustained local intravascular concentrations of heparin.