Pathophysiology
Clinical meaning
Antiplatelet agents inhibit platelet activation and aggregation at different points in the hemostatic pathway, preventing arterial thrombus formation in atherosclerotic disease. Aspirin irreversibly acetylates cyclooxygenase-1 (COX-1) in platelets, blocking the conversion of arachidonic acid to thromboxane A2 (TxA2), a potent platelet activator and vasoconstrictor. Because platelets are anucleate and cannot synthesize new COX-1, the inhibitory effect lasts the entire platelet lifespan (7-10 days). P2Y12 receptor antagonists block the ADP receptor on platelet surfaces, preventing ADP-mediated platelet activation and amplification. Clopidogrel and prasugrel are irreversible thienopyridine prodrugs requiring hepatic CYP450 conversion to active metabolites, while ticagrelor is a direct-acting, reversible cyclopentyl-triazolopyrimidine that does not require metabolic activation. Prasugrel produces more potent and consistent platelet inhibition than clopidogrel but carries higher bleeding risk. Glycoprotein IIb/IIIa (GP IIb/IIIa) inhibitors (abciximab, eptifibatide, tirofiban) block the final common pathway of platelet aggregation by preventing fibrinogen binding between activated platelets. Dual antiplatelet therapy (DAPT) combining aspirin with a P2Y12 inhibitor is the cornerstone of post-PCI and ACS management, with duration determined by stent type, ischemic risk, and bleeding risk.