Platelet-mediated
coronary thrombosis is the primary pathophysiologic mechanism of
acute coronary syndromes (ACS) and acute ischemic complications of
percutaneous coronary intervention (PCI). The final common pathway of platelet aggregation that leads to thrombotic occlusion of coronary arteries involves cross-linking of receptor
glycoprotein (
GP) IIb-IIIa on adjacent platelets by adhesive
plasma proteins, primarily
fibrinogen. Clinical trials of several
GP IIb-IIIa inhibitors have demonstrated an unequivocal clinical benefit of this potent antithrombotic
therapy in patients with ACS as well as in those undergoing PCI. Nevertheless, a significant number of patients with
ischemic heart disease may still be expected to require elective or emergency
coronary artery bypass graft (CABG)
after treatment with
GP IIb-IIIa inhibitors. In the emergency CABG setting, complications and platelet blockade with
GP IIb-IIIa inhibitors may further enhance the already heightened risk of
bleeding as compared with elective procedures. This issue became apparent in the first large clinical trial of the
GP IIb-IIIa inhibitor
abciximab (
c7E3 Fab,
ReoPro((R)); Centocor, Malvern, Pa, and Eli Lilly and Co, Indianapolis, Ind) in patients undergoing high-risk PCI. In this study, mortality rates and
bleeding complications were increased among patients undergoing emergency CABG
after treatment with a bolus plus infusion of
abciximab. Subsequent clinical experience also suggests that the potential for
bleeding complications related to emergency CABG may be increased in patients treated with
abciximab, particularly if the
drug is discontinued within 6 hours of the operation. Higher
bleeding risk with
abciximab is a result of its prolonged antiplatelet effect, which is in contrast to the readily reversible platelet blockade provided by more recently developed small-molecule
GP IIb-IIIa inhibitors such as the
peptide eptifibatide (
Integrilin((R)); COR
Therapeutics, South San Francisco, Calif, and Key
Pharmaceuticals, Kenilworth, NJ) and the nonpeptide
tirofiban HCl (
MK-383,
Aggrastat((R)); Merck & Co, Whitehouse Station, NJ). Therefore, among patients requiring CABG
after treatment with
GP IIb-IIIa inhibitors,
eptifibatide and
tirofiban may be associated with fewer
bleeding episodes than is
abciximab. With recent approval of
eptifibatide for patients with ACS and those scheduled for PCI and of
tirofiban for patients with ACS, the number of patients receiving
GP IIb-IIIa inhibitor
therapy who subsequently undergo CABG is expected to increase significantly. Strategies for improved management of
bleeding complications in these patients, including the choice of a
GP IIb-IIIa inhibitor, are clearly needed and are discussed in detail.