The therapeutic use of glycoprotein IIb/IIIa inhibitors in acute coronary syndromes

Acute coronary syndrome (ACS) embraces the clinical diagnoses of unstable angina and non-Q-wave myocardial infarction (NON-Q-MI). Conventional treatment for these conditions with aspirin, heparin and other anti-anginal drugs has its limitations. Treatment of acute symptoms with lytic therapy has not been beneficial. A large proportion of patients in this high-risk group will eventually need revascularisation due to ongoing symptoms. Platelet aggregation plays a crucial role in the pathogenesis of ACS and ischaemic complications of coronary intervention. The glycoprotein (GP) IIb/IIIa receptor, which belongs to a family of surface receptors called integrins, is the final step in this pathway. This has led to the development and use of GP IIb/IIIa inhibitors as potential therapeutic agents. Inhibitors developed so far include abciximab, a chimeric monoclonal antibody, and more recently, novel synthetic intravenous and orally administered competitive integrin blocking agents. To date, abciximab, tirofiban and eptifibatide are commercially available for clinical use. Completed clinical trials have looked at these agents as a primary treatment and as an adjunct to intervention for ACS; they have shown improvement over existing treatments, with reductions in the incidence of death, myocardial infarction (MI), refractory ischaemia and need for urgent revascularisation. Risk of bleeding and thrombocytopenia is low, and appears to be dose related and associated with concomitant treatment with high dose heparin. Cost benefit has been proven.