Glycoprotein Ilb/IIIa receptor

Administration of clopidogrel is recommended for all patients with STE ACS (Table 5—2).3 Clopidogrel blocks adenosine diphosphate receptors on platelets, preventing the expression of glycoprotein Ilb/IIIa receptors and thus platelet activation and aggregation. 

Abciximab is a first-line glycoprotein Ilb/IIIa receptor inhibitor for patients undergoing primary PCI3,15,18 who have not received fibrinolytics. It should not be administered for... 

In general, early pharmacotherapy of NSTE ACS (Fig. 5-3) is similar to that of STE ACS with three exceptions (1) fibrinolytic therapy is not administered (2) glycoprotein Ilb/IIIa receptor blockers are administered to high-risk patients for medical therapy as well as to PCI patients and (3) at this time, there are no standard quality indicators for patients with NSTE ACS who are not diagnosed with MI. 

In patients with NSTE ACS scheduled for early PCI, administration of either abciximab or eptifibatide (double bolus) is recommended. The use of tirofiban in these patients is not recommended, because it has been shown to be inferior to abciximab.2 Medical therapy with glycoprotein Ilb/IIIa receptor inhibitors in patients not undergoing PCI is reserved for higher-risk patients, such as those with positive troponin or ST-segment depression, and patients who have continued or recurrent ischemia despite other antithrombotic therapy.2... 

Doses and contraindications to glycoprotein Ilb/IIIa receptor blockers are described in Table 5-2. Major bleeding and rates of transfusion are increased with administration of a glycoprotein Ilb/IIIa receptor inhibitor in combination with aspirin and an anticoagulant,30 but there is no increased risk of intracranial hemorrhage in the absence of concomitant fibrinolytic treatment. The risk of thrombocytopenia with tirofiban and eptifibatide appears lower than that with abciximab. Bleeding risks appear similar between agents. 

Because the costs for chronic preventative pharmacotherapy are the same for primary and secondary prevention, while the risk of events is higher with secondary prevention, secondary prevention is more cost effective than primary prevention of CHD. Pharmacotherapy demonstrating cost effectiveness to prevent death in the ACS and post-MI patient includes fibrinolytics ( 2,000 to 33,000 cost per year of life saved), aspirin, glycoprotein Ilb/IIIa receptor blockers ( 13,700 to 16,500 per year of life added), (3-blockers (less than 5,000 to 15,000 cost per year of life saved), ACE inhibitors ( 3,000 to 5,000 cost per year of life saved), eplerenone ( 15,300 to 32,400 per year of life gained), statins ( 4,500 to 9,500 per year of life saved) and gemfibrozil ( 17,000 per year of life saved).49-58 Because cost-effectiveness ratios of less than 50,000 per added life-year are considered economically attractive from a societal perspective,49 pharmacotherapy described above for ACS and secondary prevention are standards of care because of their efficacy and cost attractiveness to payors. 

Lefkovits J., Plow E. F., Topol E. Platelet glycoprotein Ilb/IIIa receptors in cardiovascular medicine. N Engl J Med 1995 332, 1553-9. 

Badawy, S.I., Williams, R.C., and Gilbert, D.L., Chemical stability of an ester prodrug of a glycoprotein Ilb/IIIa receptor antagonist in solid dosage forms,. Pharm. Sci., 88, 428,1999. 

C. Aspirin inhibits platelet cyclooxygenase. Abciximab, a monoclonal antibody, binds to and inhibits the platelet glycoprotein Ilb/IIIa receptor. Dipyridamole inhibits platelet cyclic AMP phosphodiesterase and raises cyclic AMP levels. Eptifibatide binds to the glycoprotein Ilb/IIIa complex. 

Mechanism of Action A glycoprotein Ilb/IIIa receptor inhibitor that rapidly inhibits platelet aggregation by preventing the binding of fibrinogen to GP Ilb/IIIa receptor sites on platelets. Therapeutic Effect Prevents closure of treated coronary arteries. Prevents acute cardiac ischemic complications. 

Mechanism of Action An aggregation inhibitor that inhibits the release of adenosine diphosphate from activated platelets, which prevents fibrinogen from binding to glycoprotein Ilb/IIIa receptors on the surface of activated platelets. TherapeuticEffect Inhibits platelet aggregation and thrombus formation. 

ReoPro (Abciximab) Glycoprotein Ilb/IIIa receptor Chimeric Fab Complication of coronary angioplasty 1994... 

Atwater BD, Roe MT, Mahaffey KW. Platelet glycoprotein Ilb/IIIa receptor antagonists in non-ST segment elevation acute coronary syndromes a review and guide to patient selection. Drugs. 2005 65 313-324. 

Bates, E. R., McGillem, M. J., Mickelson, J. K, Pitt, B., and Mancini, G. B. (1991). A monoclonal antibody against the platelet glycoprotein Ilb/IIIa receptor complex prevents platelet aggregation and thrombosis in a canine model of coronary angioplasty. Circulation 84, 2463-2469. 

EPILOG Investigators (1997). Platelet glycoprotein Ilb/IIIa receptor blockade and low-dose heparin during percutaneous coronary revascularization. N. Enol. J. Med. 336, 1689-1696. 

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