Cyclooxygenase Inhibitors and the Antiplatelet Effects of Aspirin

The antiplatelet effects of aspirin are caused by the irreversible inhibition of the activity of the enzyme cyclooxygenase. In contrast, nonsteroidal antiinflammatory drugs (NSAIDs) are reversible inhibitors of this activity and have only transient effects on platelet function. This study found that pretreatment with ibuprofen before the administration of aspirin blocked the antiplatelet effects of aspirin. Neither the cyclooxygenase-2 inhibitor rofecoxib nor acetaminophen had this blocking effect. Nonsteroidal antiinflammatory drugs (NSAIDs) are commonly prescribed, 1 and the use of aspirin has increased since it was shown to reduce the risk of myocardial infarction and stroke. 2 , 3 Aspirin acts by irreversibly acetylating a serine residue at position 529 in platelet prostaglandin G/H synthase, 4 an enzyme colloquially known as cyclooxygenase. The predominant product of cyclooxygenase in platelets is thromboxane A 2 . 5 The anucleate platelet affords a unique target for aspirin, since once cyclooxygenase has been acetylated by aspirin, the substrate's access to its active site is impeded for the lifetime of the platelet. Thus, the formation of thromboxane A . . .