The evolving role of platelet glycoprotein IIb IIIa inhibitors in the management of acute coronary syndromes

OBJECTIVE: TO briefly discuss the pathophysiology of acute coronary syndrom es (ACS) and to present the clinical data currently available regarding the use of platelet glycoprotein (GP) IIb/IIIa inhibitors in the management of ACS. DATA SOURCES: Literature on antithrombotic therapy in ACS was identified us ing a MEDLINE search (January 1988-September 1998), along with the Agency o n Health Care Policy and Research guidelines for the management of unstable angina. Abstracts from recent scientific meetings were also reviewed. STUDY SELECTION: Review articles from the cardiology literature (pathophysi ology) and randomized, controlled clinical trials of currently approved pla telet GP IIb/IIIa inhibitors in ACS were evaluated. Ex vivo platelet aggreg ation studies and pharmacology literature were also included. Abstract data were included to illustrate specific points when published literature was not available. DATA EXTRACTION: Study data were evaluated based on study design, outcome p arameters, and adverse drug reactions. Clinical information from review art icles was evaluated based on applicability to the treatment of ACS. DATA SYNTHESIS: Platelet adhesion and aggregation are pivotal events in the pathophysiology of ACS. The GP IIb/IIIa inhibitors represent a new and uni que class of drugs that block fibrinogen and von Willebrand factor-mediated platelet aggregation, the common end point of all biologic pathways of pla telet aggregation. Three agents are currently approved by the Food and Drug -Administration: abciximab, a monoclonal antibody; eptifibatide, a syntheti c peptide; and tirofiban, a synthetic nonpeptide. CONCLUSIONS: Clinical trial data demonstrate efficacy of all three GP IIb/I IIa inhibitors in reducing the combined end point of morbidity and mortalit y in patients undergoing angioplasty. Eptifibatide and tirofiban also reduc e the combined end point of morbidity and mortality in patients with unstab le angina. These data expand the present role of platelet GP IIb/IIIa inhib itors by providing evidence for their effectiveness in the medical treatmen t of ACS. However, the specific role that these agents will have in the man agement of ACS is yet to be fully defined.