Clinical challenges of platelet glycoprotein IIb/IIIa receptor inhibitor therapy: bleeding, reversal, thrombocytopenia, and retreatment.
Randomized clinical trials of glycoprotein IIb/IIIa integrin inhibition during percutaneous coronary intervention and as adjunctive treatment of acute coronary syndromes have shown impressive clinical efficacy in reducing the morbidity and mortality rates of cardiovascular disease. Three agents are currently available in the United States: abciximab (ReoPro), eptifibatide (Integrilin), and tirofiban (Aggrastat). Pharmacodynamic studies show that abciximab is a high-affinity agent with a low dissociation constant; eptifibatide and tirofiban are high-specificity agents with higher dissociation constants and concentration-dependent antiplatelet effects. This article first reviews the relevant pharmacokinetic and pharmacodynamic properties of each of the agents. These principles are then applied to a discussion of the 4 primary clinical issues concerning their use: prevention of untoward bleeding, algorithms for acute reversal, recognition and treatment of thrombocytopenia, and the issue of readministration.
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