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[Anti-integrins--new platelet function inhibitors for therapy and prevention of acute coronary syndrome].

Abstract：

:Acute occlusion of a large coronary artery by a platelet thrombus is a life-threatening event. Intravasal thrombus generation in most cases is caused by a disturbed interaction between platelets and the vessel wall, with accompanying platelet hyperreactivity, local adhesion to the vessel wall, activation and aggregate formation after binding of soluble fibrinogen to the activated GP IIb/IIIa-receptor. Conventional antiplatelet agents, such as aspirin or ticlopidine/clopidogrel, inhibit uncontrolled local agonist-induced signal transduction within the platelet by interfering with the thromboxane A2 and ADP pathway, respectively. This results in an activation of the platelet GP IIb/IIIa-receptor and, finally, in a reduced capacity of fibrinogen binding. Antiintegrins inhibit cell-cell and cell-matrix interactions. Antagonists of the platelet integrin alpha IIB/beta 3 (GP IIb/IIIa) (eg. Abciximab, Eptifibatide, Tirofiban) inhibit platelet adhesion and aggregation via their RGD (KGD) binding sequence, resulting in reduced fibrinogen binding. The significance of inhibition of other RGD-containing adhesion molecules (von Willebrand Factor, Vitronectin) with respect to the clinical efficacy of these compounds is stil under debate. GP IIb/IIIa-antagonists are the most effective inhibitors of platelet function and in high doses, may cause complete inhibition of platelet aggregation and maximum prolongation of bleeding time. The clinical efficacy of GP IIb/IIIa-antagonists for acute percutaneous coronary interventions and in the management of the acute coronary syndrome is established. Whether Abciximab and low-molecular weight intravenous compunds (Eptifibatide, Tirofiban, Lamifiban) are equipotent, remains to be demonstrated by controlled comparative studies. Orally active low-molecular-weight compounds (Sibrafiban, Xemilofiban and others) are currently undergoing clinical trials. Whether these substances are superior to oral aspirin and/or clopidogrel in long-term prevention of acute arterial vessel occlusions remains to be determined.

journal_name

Wien Klin Wochenschr

journal_title

Wiener klinische Wochenschrift

authors

Schrör K

subject

Has Abstract

pub_date

1999-02-12 00:00:00

pages

90-7

issue

eissn

0043-5325

issn

1613-7671

journal_volume

111

pub_type

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[Anti-integrins--new platelet function inhibitors for therapy and prevention of acute coronary syndrome].