Aspirin's Mechanism of Action in Preventing Cardiovascular Events
Aspirin prevents myocardial infarction and ischemic stroke by irreversibly inhibiting the cyclooxygenase-1 (COX-1) enzyme through acetylation of serine residue 529, which permanently blocks thromboxane A2 production and prevents platelet aggregation for the entire 7-10 day lifespan of the platelet. 1, 2
The correct answer is C: Inhibition of cyclo-oxygenase enzyme to prevent platelet aggregation.
Molecular Mechanism
Aspirin selectively acetylates the hydroxyl group of serine at position 529 (Ser529) within the polypeptide chain of platelet cyclooxygenase-1 (COX-1), permanently inactivating this enzyme 1
This acetylation blocks the conversion of arachidonic acid to prostaglandin H2 (PGH2), the precursor of thromboxane A2 (TXA2), a potent vasoconstrictor and platelet aggregator 1, 2
The irreversible nature of this inhibition means platelets remain functionally impaired for their entire lifespan, as mature platelets cannot synthesize new COX-1 enzyme 3, 2
Why the Other Options Are Incorrect
Option A is incorrect: Aspirin does not bind to activated clotting factors Xa and IIa—this describes the mechanism of direct oral anticoagulants like rivaroxaban, not aspirin 1
Option B is incorrect: Aspirin does not inhibit platelet phospholipids themselves; rather, it blocks the enzyme (COX-1) that converts arachidonic acid (derived from membrane phospholipids) into thromboxane A2 1, 2
Option D is incorrect: Inhibition of vitamin K-dependent factors describes the mechanism of warfarin, not aspirin 1
Clinical Pharmacology Supporting This Mechanism
Despite aspirin's half-life of only approximately 20 minutes in circulation, its anti-thrombotic effect persists for 24-48 hours due to permanent platelet COX-1 inactivation 1, 2
The anti-thrombotic effect is saturable at doses of 75-100 mg daily, consistent with complete COX-1 inhibition at these doses 1, 2
Low-dose aspirin (75-150 mg) is as effective as higher doses (300-1500 mg) for preventing vascular events, confirming that complete COX-1 blockade is achieved at lower doses 1
Clinical Evidence
A meta-analysis of 287 randomized studies comprising 135,000 patients demonstrated a 25-30% reduction in cardiovascular events (MI, stroke, or death) with aspirin treatment in high-risk patients 1
In acute MI, aspirin (160 mg daily) produces a 30% proportional odds reduction in vascular events, preventing 40 vascular events per 1,000 patients treated 1
The mechanism is definitively linked to COX-1 inhibition, as other proposed mechanisms (such as anti-inflammatory effects) are incompatible with the unique dose-response and duration properties observed in clinical trials 1