Aspirin

Aspirin, considered the prototypic platelet antagonist, has been available for over a century and currently represents a mainstay both in the prevention and treatment of vascular events that include stroke, myocardial infarction, peripheral vascular occlusion, and sudden death. Aspirin irreversibly acetylates cyclooxygenase (COX), impairing prostaglandin metabolism and thromboxane A2 (TXA2) synthesis. As a result, platelet aggregation in response to collagen, adenosine diphosphate (ADP), and thrombin (in low concentrations) is attenuated (Roth and Majerus, 1975). Because aspirin more selectively inhibits COX-1 activity (found predominantly in platelets) than COX-2 activity (expressed in tissues following an inflammatory stimulus), its ability to prevent platelet aggregation is seen at relatively low doses, compared with the drug’s potential antiinflammatory effects, which require much higher doses (Patrono, 1994). Several alternative mechanisms of platelet inhibition by aspirin have been proposed, including: (1) inhibition of platelet activation by neutrophils and (2) enhanced nitric oxide production. In addition, aspirin may prevent the progression of atherosclerosis by protecting low-density lipoprotein (LDL) cholesterol from oxidation and scavenging hydroxyl radicals. Following oral ingestion, aspirin is promptly absorbed in the proximal gastrointestinal (GI) tract (stomach, duodenum), achieving peak serum levels within 15 to 20 minutes and platelet inhibition within 40 to 60 minutes. Enteric-coated preparations are less well absorbed, causing an observed delay in peak serum levels and platelet inhibition to 60 and 90 minutes, respectively. The antiplatelet effect occurs even before acetylsalicylic acid is detectable in peripheral blood, probably from platelet exposure in the portal circulation. The plasma concentration of aspirin decays rapidly with a circulating half-life of approximately 20 minutes. Despite the drug’s rapid clearance, platelet inhibition persists for the platelet’s life span (7 ± 2 days) due to aspirin’s irreversible inactivation of COX-1. Because 10% of circulating platelets are replaced every 24 hours, platelet activity (bleeding time, primary hemostasis) returns toward normal (≥50% activity) within 5 to 6 days of the last aspirin dose (O’Brien, 1968). A single dose of 100 mg of aspirin effectively reduces the production of TXA2 in many (but not all) individuals.