What is the mechanism of action of low-dose aspirin in cardiovascular prevention?

• A. Irreversible inhibition of platelet COX-1
• B. Reversible inhibition of COX-2
• C. Inhibition of P2Y12 receptor
• D. Inhibition of phosphodiesterase

Answer: (A)

Low-dose aspirin provides cardiovascular protection by irreversibly inhibiting a platelet enzyme called cyclooxygenase-1. In platelets, COX-1 normally converts arachidonic acid into thromboxane A2, a potent promoter of platelet aggregation and vasoconstriction. By acetylating a specific serine in COX-1, aspirin stops thromboxane A2 production for the life of the platelet. Since platelets cannot make new proteins, this effect lasts about 7 to 10 days, until new platelets enter circulation. The result is a reduced tendency for platelets to clump together, which lowers arterial thrombus formation. Endothelial cells can synthesize new COX and keep producing prostacyclin, which helps prevent platelet aggregation, so the overall effect favors anti-thrombotic protection with low-dose aspirin. In contrast, blocking COX-2, inhibiting the P2Y12 receptor, or inhibiting phosphodiesterase are actions of other drugs or higher-dose regimens and are not the primary mechanism for low-dose aspirin’s antiplatelet effect.