Platelet GPIIb/IIIa Receptor Antagonists in Human Ischemic Brain Disease

Rudiger   J.   Seitz; Mario      Siebler

Abstract

The goal of acute stroke therapy is to salvage brain tissue by rapid cerebral artery recanalization to improve microcirculation. A major drawback of fibrinolysis is the activation of platelets leading to a high rate of re-occlusion. Antagonists of the platelet GPIIb/IIIa-receptor inhibit the binding of fibrinogen to platelets counteracting secondary thrombus formation. Also, they were shown to suppress thrombembolus formation and to limit lesion development in cerebral ischemia. We review the literature concerning the use of intravenously administered GPIIb/IIIa-receptor antagonists abciximab, eptifibatide and tirofiban for the treatment of patients with acute ischemic brain infarction. In multicenter, prospective, randomized and placebo-controlled trials abciximab had a higher cerebral bleeding risk, while tirofiban did not increase hemorrhage. When combined with fibrinolysis, abciximab and tirofiban were found to improve cerebral artery recanalization and tissue reperfusion resulting in reduced infarct volumes and improved neurological outcome. Thus, GPIIb/IIIareceptor antagonists have a great potential for the treatment of acute stroke.

Keywords: Stroke, fibrinolysis, reperfusion, hemorrhage, receptor polymorphism

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