Low molecular weight heparin in unstable coronary artery disease

Since the recognition that any thrombosis overlying a ruptured atherosclerotic plaque is a central component of the pathogenesis of unstable coronary artery disease (CAD), a number of antithrombotic treatment strategies have been investigated in randomised clinical trials. Aspirin reduces the occurrence of symptomatic and silent ischaemia, myocardial infarction (MI) and death in patients with unstable CAD, both in the acute phase and during continued long-term treatment and is now considered routine therapy. The addition of unfractionated heparin infusion further reduces cardiac events during the treatment period, but is not associated with any sustained benefits during long-term follow-up. Low molecular weight heparins (LMWHs) are completely absorbed by the sc. route. A predictable anticoagulant effect is maintained by sc. injections every 12 - 24 h without laboratory monitoring. The FRISC trial demonstrated that, in conjunction with aspirin, the LMWH dalteparin reduced death and MI by more than 50% in the acute phase. Four similar trials have directly compared LMWH with unfractionated heparin and demonstrated at least the same efficacy in the acute phase, treated between three and eight days. The LMWH enoxaparin was more effective at reducing death or MI than unfractionated heparin infusion during the three days of treatment, an effect which lasted up to 12 months. Prolonged out-patient treatment beyond the acute phase has been evaluated in four trials. It was demonstrated, in two of these trials, that continuing twice-daily injections of dalteparin further reduced the risk of death, MI and need for revascularisation at least during the initial six weeks of treatment. This effect was confined, however, to patients with signs of myocardial damage, i.e., elevation of troponin, at admission. During prolonged out-patient treatment, there is an increased risk of severe bleeding due to the combination of LMWH with aspirin. Based on successful results, the LMWHs, having the convenience of treatment and the option for continuation in an out-patient setting, should replace unfractionated heparin as the routine treatment in unstable CAD. If an early invasive procedure is considered, the LMWH therapy should be continued until the intervention as a 'bridge-to-revascularisation'. New antiplatelet agents are also emerging as additional useful tools for treating these patients, thus it is urgent to evaluate the comibination of these new therapies with the LMWHs.