Platelet inhibitor agents in cardiovascular disease: An update

Abstract

Platelets interact with the coagulation and fibrinolytic systems in the maintenance of hemostasis. However, these physiologic mechanisms may become pathologic, requiring prevention and treatment. In this review, the following clinical developments are analyzed: 1) the role of platelets in thrombogenesis; 2) the pharmacology of platelet inhibitory agents; and, most important, 3) the results of recent randomized trials of platelet inhibitor agents in different cardiovascular disorders. Aspirin reduces mortality and infarction rates in unstable angina and significantly decreases vascular mortality in acute myocardial infarction. Platelet inhibitors decrease mortality and recurrent cardiovascular events in the chronic phase after myocardial infarction. They also decrease vein graft occlusion rates after coronary bypass surgery. Although platelet inhibitors are beneficial in preventing acute vessel occlusion during coronary angioplasty, they are ineffective in preventing chronic restenosis. Antiplatelet agents, combined with warfarin, reduce thromboembolic events in patients with a mechanical prosthesis. Platelet inhibitors are also effective in secondary prevention of vascular events in patients with cerebrovascular disease. Finally, the use of aspirin for primary prevention of cardiovascular disease is still evolving, particularly in individuals at high risk. In conclusion, platelet inhibitors are effective in patients with a variety of cardiovascular disorders. The best studied, most inexpensive and least toxic agent is aspirin at a daily dose of 160 to 325 mg. Studies using new platelet inhibitor agents with different mechanisms of action are currently underway.

Coronary artery disease and cardiac events with asymptomatic and symptomatic cerebrovascular disease.

“…The use of aspirin has been shown to reduce mortality and myocardial infarction rates in patients with unstable angina and is probably useful in primary prevention of myocardial infarction in patients who are at high risk for developing significant CAD. 37 After our initial work-up, 17 patients were started on medical therapy for CAD, two who developed angina underwent successful percutaneous transluminal coronary angioplasty, and two underwent coronary artery bypass grafting.…”

Aspirin-Induced Conformational Changes in Platelet Membrane in Subjects with Stroke

“…The great majority of acute strokes (85%) in western societies are isch emic in origin, usually arising from thrombot ic occlusion of atherosclerotic carotid or cere bral arteries at a site of flow-limiting stenosis [1][2][3]. Platelets are intimately involved in the pathophysiology of atherosclerosis, since they can release vasoactive and platelet pro-aggregatory mediators which in turn stimulate fur ther platelet activation and vasoconstriction [1][2][3][4], In addition, platelets have been shown to be a major structural component of the ath erosclerotic plaque. Apart from the release of vasoactive substances and decreased survival, little is known about the role of platelets in stroke.…”

Inhibitory Effects of a Novel Antiplatelet Agent, E5510, on Collagen-Induced Platelet-Derived Growth Factor Release and Aggregation of Human Platelets In Vitro

“…Within 30 min after balloon injury in vivo, platelet factor 4 (PF4), one of the constituents in the alpha-gran ules of platelets, can be detected throughout the intima and media (15). Because PF4 and other platelet-secreted proteins such as PDGF reside in the same granule popula tion (16) and are secreted in response to the same stimuli, they also enter the vessel wall after the removal of the en dothelial cells. Therefore, E5510 may have clinical poten tial for the inhibition of PDGF release from platelets ad herent to the subendothelial components after balloon angioplasty, at the same plasma concentrations that can cause inhibition of platelet aggregation.…”