Therapeutic inhibition of platelet function in stroke

Platelet-dependent thrombotic- and thromboembolic-occlusive events are the usual cause of ischemic strokes. Antiplatelet strategies target one of the three platelet recruitment pathways (thromboxane A2, adenosine diphosphate, or thrombin) or the common cohesion pathway involving integrin alphaIIbbeta3 fibrinogen receptors. Aspirin selectively and irreversibly interrupts TxA2 and decreases events by 20-25%. Clopidogrel selectively and irreversibly inactivates platelet-ADP receptors and reduces events by 30-35%. Additive effects are produced by combining aspirin and clopidogrel. Integrin alphaIIbbeta3 fibrinogen receptor antagonists, such as abciximab, produce dose-dependent inhibition of platelet recruitment and thrombo-occlusive events, regardless of the agonist(s) initiating platelet activation, but correspondingly impair platelet hemostatic function. Because chronic antiplatelet therapy has the potential for producing abnormal bleeding it is important for current clinical trials to evaluate the benefit risk relationship.