Aspirin for primary prevention of cardiovascular events in diabetes.

Abstract

Aspirin is probably the most widely used and least expensive drug in existence. The value of extracts of willow bark in controlling pain and fever was recognized in 400 BC by Hippocrates. In the 19th century, salicylic acid was identified as the active principle, and in 1899, Felix Hoffman synthesized acetylsalicylic acid. Shortly thereafter, Heinrich Dreser, director of pharmacological research for Bayer and Company, led the clinical trials that demonstrated efficacy and named this new drug aspirin. In the 20th century, aspirin attracted the attention of physicians interested in cardiovascular disease after it was found that platelet cyclooxygenase, the enzyme that converts arachidonic acid to prostaglandins G2 and H2, was irreversibly inhibited in man by very low doses of aspirin. This blockade would inhibit thromboxane production, platelet aggregation, and vasoconstriction. Meta-analyses of large-scale clinical trials have shown that aspirin will reduce the risk for major cardiovascular events by ∼25% in high-risk individuals (1). People with type 2 diabetes have a risk of myocardial infarction, stroke, and cardiovascular death that is at least two- to fourfold greater than that of age- and sex-matched control subjects. Individuals with diabetes have been shown to have platelets that are unusually sensitive to aggregating agents and manufacture prostaglandin metabolites and thromboxane in excess. Platelets from diabetic subjects also display increased adhesiveness via nonprostaglandin-mediated pathways. Two of these pathways are mediated by the ADP receptor and fibrinogen binding to the GPIIb/IIIa complex. Fibrinolytic activity is often suppressed in type 2 diabetes, predominantly via inhibitory actions of plasminogen activator inhibitor (PAI-1) on fibrinolysis. Approximately 90% of the …