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.