Acute and prolonged treatment with low-molecular-weight heparin therapy in patients with unstable coronary artery disease.

Unstable angina and non-ST-segment elevation myocardial infarction (MI) are known as unstable coronary artery disease (UCAD). They are syndromes that share a common pathobiology and represent a frequently encountered and potentially life-threatening medical condition. Acute-phase treatment with aspirin is associated with a significant reduction in death and non-fatal MI in patients with UCAD. This benefit is enhanced by the addition of unfractionated heparin (UFH) to the treatment strategy; however, UFH requires careful monitoring and titration. In contrast, low-molecular-weight heparins (LMWHs), produced by chemical or enzymatic depolymerization of UFH, yield a predictable and consistent pharmacokinetic profile and anticoagulant response making them an attractive alternative treatment to UFH in patients with UCAD. In several studies, acute-phase treatment with LMWH has been shown to be at least as effective and safe as UFH. The optimal duration of treatment with LMWH is an important question that has been influenced by the observation that reactivation of coagulation occurs following the early and abrupt discontinuation of heparin treatment. In early trials, such as FRISC (Fragmin during instability in coronary artery disease) and FRIC (Fragmin in unstable coronary artery disease), the results of extended treatment were inconclusive; however, the trial populations included patients of relatively low risk and used a once-daily dosing regimen. In the TIMI 11B (Thrombolysis in myocardial infarction) extended treatment beyond the few days of acute treatment with enoxaparin did not add to the beneficial LMWH effect, but in this study 40% of the high-risk patients did not continue on extended treatment. The findings derived from the FRISC II trial, which used a twice-daily dose of dalteparin sodium, suggest a benefit for up to 45 days with extended treatment in high-risk UCAD patients. Although an early invasive treatment strategy is particularly beneficial, patients in whom early revascularization is not possible should be considered for extended treatment with dalteparin sodium awaiting percutaneous coronary intervention.