Dual Antiplatelet Therapy for Prevention of Recurrent Ischemic Events

Jean Nappi, PharmD, Fccp, Bcps; Robert Talbert, PharmD, Fccp, Bcps


Am J Health Syst Pharm. 2002;59(18) 

In This Article

Pathophysiology of Atherosclerosis

Atherosclerosis is an insidious systemic process involving multiple vascular beds, including the cerebral, coronary, and peripheral arteries.[7,8] Acute manifestations of atherosclerotic disease result when eroded or disrupted plaque surfaces become substrates for thrombus formation (atherothrombosis).[9,10,11] Platelet aggregation, a key process in the development of atherothrombosis, is triggered by thrombogenic plaque components, exposed collagen or tissue factor in atherosclerotic vessels, high-shear blood flow rates caused by arterial stenosis, or residual thrombin at the surface of an old mural thrombus.[9,10,11,12] The ensuing platelet cascade is characterized by platelet adhesion, activation, release, and aggregation.[13] Platelet adhesion is mediated by the binding of von Willebrand factor to the glycoprotein (GP) IIb receptor on the platelet membrane.[14] The activation process is initiated when at least one agonist (e.g., thrombin, adenosine diphosphate [ADP], collagen, serotonin, and epinephrine) stimulates platelet membrane receptors to induce the release of activating agents, such as ADP, platelet-derived growth factor, fibrinogen, and thromboxane A2.[14] Thus, multiple agonists and mechanisms are responsible for promoting platelet activation and intensifying aggregation.[11,14] The culmination of platelet aggregation into the formation of a platelet plug is mediated by the GP IIb/IIIa receptor, which serves as the platelet receptor for fibrinogen.[15] The newly formed platelet plug is the core for an arterial thrombus that may impede or occlude arterial blood flow leading to the development of ischemic vascular events.[14]

Atherosclerotic plaque rupture is one of the inciting events in the progression of platelet activation, aggregation, and thrombus formation.[16,17] The stability or vulnerability of the plaque determines its likelihood to rupture. Atherosclerotic plaque with a thick fibrous cap is more stable than that with a thin cap. The presence of inflammatory cells, which secrete enzymes that degrade collagen and other GPs, in the cap region makes the plaque more likely to rupture. Disturbances in blood flow, hypertension, infection, and irritants in tobacco smoke can negatively impact the arterial endothelium and create a local environment that favors plaque vulnerability and rupture.[10,18] Plaques with large lipid cores are more vulnerable to rupture.[19]


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