REVIEW ARTICLES
Platelet glycoprotein IIb/IIIa receptor blockade in coronary artery disease
A. Michael Lincoff, MD, FACC*,
Robert M. Califf, MD, FACC and
Eric J. Topol, MD, FACC*
* Department of Cardiology, The Cleveland Clinic Foundation, Cleveland, Ohio, USA
Duke Clinical Research Institute, Duke University, Durham, North Carolina, USA
Manuscript received July 1, 1999;
revised manuscript received November 9, 1999,
accepted January 5, 2000.
Reprint requests and correspondence: Dr. A. Michael Lincoff, Department of Cardiology, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, Ohio 44195
New strategies for profound inhibition of platelet activity at the injured coronary plaque focus on blockade of the platelet surface membrane glycoprotein IIb/IIIa receptor, which binds circulating fibrinogen or von Willebrand factor and crosslinks platelets as the final common pathway to platelet aggregation. Intravenous agents directed against this receptor include the chimeric monoclonal antibody fragment abciximab, the peptide inhibitor eptifibatide and nonpeptide mimetics tirofiban and lamifiban. Over 33,000 patients have been evaluated in 11 large-scale, placebo-controlled trials of these agents.
During percutaneous coronary intervention, an absolute reduction of 1.5% to 6.5% in the 30-day risk of death, myocardial infarction or repeat urgent revascularization has been observed, with some variability in treatment effect among the agents tested (abciximab, eptifibatide and tirofiban). Treatment effect is achieved early with every modality of revascularization and is maintained over the long-term (up to three years). Increased bleeding risk may be minimized by reduction and weight-adjustment of concomitant heparin dosing. In the acute coronary syndromes without ST segment elevation, absolute 1.5% to 3.2% reductions in 30-day rates of death or myocardial (re-) infarction have been achieved with two to four day courses of eptifibatide or tirofiban. Clinical benefit accrues during the period of drug infusion and is durable. Treatment effect may be enhanced among patients undergoing early coronary revascularization, with evidence of stabilization before intervention and suppression of postprocedural ischemic events. Thus, blockade of the platelet glycoprotein IIb/IIIa receptor reduces ischemic complications when used as an adjunct to percutaneous coronary intervention or the management of acute ischemic syndromes.
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Abbreviations and Acronyms
| | CAPTURE | = C7E3 AntiPlatelet Therapy in Unstable REfractory angina | | EPIC | = Evaluation of c7E3 for Prevention of Ischemic Complications | | EPILOG | = Evaluation in PTCA to Improve Long-term Outcome with abciximab GP IIb/IIIa blockade | | EPISTENT | = Evaluation of Platelet Inhibition in STENTing | | HACA | = human antichimeric antibody | | IMPACT II | = Integrilin to Minimize Platelet Aggregation and Coronary Thrombosis-II | | MI | = myocardial infarction | | PARAGON | = Platelet IIb/IIIa Antagonism for the Reduction of Acute Coronary Syndrome events in the Global Organization Network | | PRISM | = Platelet Receptor Inhibition in Ischemic Syndrome Management | | PRISM PLUS | = Platelet Receptor Inhibition in Ischemic Syndrome Management in Patients Limited by Unstable Signs | | PURSUIT | = Platelet IIb/IIIa in Unstable angina: Receptor Suppression Using Integrilin Therapy | | RAPPORT | = ReoPro And Primary PTCA Organization and Randomized Trial | | RESTORE | = Randomized Efficacy Study of Tirofiban for Outcomes and REstenosis |
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