Low-molecular-weight heparins and unstable angina--current perspectives

Thrombosis is responsible for most acute manifestations of coronary artery disease, including unstable angina and non-Q-wave myocardial infarction (MI). Antiplatelet therapy plays a major role in reducing the risk of ischaemic events in such patients. Since thrombin generation is key in the pathogenesis of thrombosis, recent studies have focussed on thrombin inhibition in the management of acute ischaemia. Heparin is the most widely used anticoagulant for acute management of thrombosis and is the treatment of choice in the prevention and treatment of venous thromboembolism. Heparin given in therapeutic doses intravenously has been shown to be more effective than aspirin at reducing the risk of death or MI in patients with unstable angina. Low-molecular-weight heparins (LMWHs) have improved pharmacologic and pharmacokinetic properties over standard heparin that may result in greater efficiency and safety. LMWH may be given in fixed doses subcutaneously without monitoring, resulting in greater clinical utility and cost-effectiveness compared with standard heparin. A number of LMWHs-dalteparin, enoxaparin and nadroparin-have been evaluated in unstable angina. In a small open trial, nadroparin reduced the risk of ischaemic outcomes compared with aspirin alone or a combination of aspirin and standard heparin. Dalteparin has been evaluated in two large clinical trials in the management of unstable angina. The low-Molecular-Weight Heparin (Fragmin) During Instability in Coronary Artery Disease (FRISC) trial showed that dalteparin resulted in a 63% reduction in risk of death or acute MI compared with aspirin alone. The Fragmin in Unstable Coronary Artery Disease (FRIC) trial showed that dalteparin was as effective as intravenous heparin. Enoxaparin resulted in a statistically significant 16% reduction in the combined outcome of death, MI and recurrence of angina in comparison with standard heparin in the Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q-Wave Coronary Events (ESSENCE) trial. There is accumulating evidence that LMWHs are safe and effective alternatives to standard heparin in unstable coronary artery disease and that they offer practical and therapeutic advantages.