New frontiers in the management of unstable coronary artery disease.

Thrombotic occlusion is responsible for most acute manifestations of coronary artery disease, including unstable angina and non-Q-wave myocardial infarction. Antiplatelet therapy plays a major role in reducing the risk of ischemic events in such patients. Since thrombin generation is vital to the pathogenesis of thrombosis, recent studies have focused on thrombin inhibition in the management of acute ischemia. Heparin is the most widely used anticoagulant for acute management of thrombosis and is the treatment of choice in preventing and treating venous thromboembolism. Given in therapeutic doses intravenously, it is more effective than aspirin in reducing the risk of death or myocardial infarction in patients with unstable angina. Low-molecular-weight (LMW) heparins have improved pharmacologic and pharmacokinetic properties over standard heparin that may result in greater efficacy and safety. LMW heparins may be given in a fixed dose subcutaneously without monitoring, resulting in greater clinical utility and cost-effectiveness compared with standard heparin. Given subcutaneously in fixed, weight-adjusted doses they are more effective and safer than intravenous heparin in treating deep-vein thrombosis. Several studies have evaluated LMW heparins in unstable angina. In a small open trial, LMW heparin (nadroparin) reduced the risk of acute myocardial infarction compared with aspirin alone or a combination of aspirin and standard heparin. In 2 large clinical trials, LMW heparin (dalteparin) has been shown to be effective in the management of unstable angina with a 63% reduction in risk of death or acute myocardial infarction over patients treated with aspirin alone (Fragmin during Instability in Coronary Artery Disease; FRISC) and to be as effective as intravenous heparin (Fragmin in Unstable Coronary Artery Disease; FRIC).