Glycoprotein IIb/IIIa inhibitors and acute coronary syndromes: summary report of the full submission to NICE, and beyond.

Acute coronary syndromes constitute a spectrum of clinical conditions and can be divided into non-ST segment elevation (unstable angina and non-Q wave myocardial infarction) and ST segment elevation myocardial infarction. They are major causes of morbidity and mortality. Hospital admissions for unstable angina are increasing (estimated approximately 130 000 patients per year in the UK) and have now exceeded those for acute myocardial infarction, with the incidence of death or myocardial infarction in hospital at 4.9% and by six months 12%. Plaque disruption, platelet adherence, platelet activation (mediated by various agents) and an ensuing platelet thrombus lead to subtotal or complete occlusion of the coronary artery. It is hypothesised that platelet thrombi can embolise downstream giving rise to microvascular platelet aggregation and myocardial damage. The evidence for inflammation as a significant factor in patients with acute coronary syndromes is raised C-reactive protein (a measure of interleukin 6 and cytokine activation) which carries a worse prognosis. The glycoprotein (GP) IIb/IIIa receptor represents a pathway for platelet aggregation and is the most abundant receptor found on platelet membrane surfaces (40 000 to 80 000 per platelet). The activated GP IIb/IIIa receptor binds with the soluble ligands fibrinogen and von Willebrand factor causing platelet adherence, generation of a platelet mass, and thrombus formation. Pioneering research by Coller and colleagues with a murine derived monoclonal antibody directed against the GP IIb/IIIa receptor led to the development of a chimeric monoclonal antibody Fab fragment compound known as c7E3 Fab or abciximab (Reopro). Development of synthetic molecules of low molecular weight followed and two are commercially available (tirofiban (Aggrastat) and eptifibatide (Integrilin)). They diVer from abciximab by mimicking the arginine-glycine-aspartic acid sequence and thus competitively inhibit fibrinogen binding to the GP IIb/IIIa receptor. They have a shorter duration of action and are specific to the GP IIb/IIIa receptor.