Acetylsalicylic acid was first marketed as aspirin in 1899 and used extensively over the next decades as a prototypic non-steroidal anti-inflammatory drug (NSAID). Following the seminal discoveries made by John Vane and Bengt Samuelsson in the early 1970s on the biochemistry and pharmacology of arachidonic acid metabolism, the molecular mechanism of action of aspirin in inhibiting platelet function was elucidated by the elegant studies of Philip Majerus. The development of whole blood thromboxane (TX)B2 production as a biochemical endpoint for human studies allowed the characterization of the doseand time-dependence of the antiplatelet effect of aspirin in the early 1980s. This, in turn, provided the rationale for a new wave of randomized clinical trials employing daily doses 10– to 50-fold lower than used empirically in the past. A large database consisting of over 100 clinical trials of aspirin prophylaxis in a wide range of vascular disorders now provides solid grounds for assessing the balance between benefits and risks in the whole spectrum of atherothrombosis.

Mechanism of action of aspirin

The best characterized mechanism of action of the drug is related to its capacity to inactivate permanently the cyclooxygenase (COX) activity of prostaglandin H-synthase (PGHS)-1 and -2 (also referred to as COX-1 and COX-2). These isozymes catalyse the first committed step in prostanoid biosynthesis, i.e., the conversion of arachidonic acid to PGH2. PGH2 is the immediate precursor of PGD2, PGE2, PGF2α, PGI2 and TXA2. COX-1 and COX-2 are homodimers of a ∼72 kDa monomeric unit.