Dual antiplatelet therapy (DAPT) with aspirin and a P2Y₁₂ inhibitor is the pharmacological cornerstone of ST-segment elevation myocardial infarction (STEMI) management. The evolution from clopidogrel to the more potent agents prasugrel and ticagrelor has improved ischaemic outcomes in PCI-treated patients, while cangrelor provides an intravenous alternative when oral absorption is compromised. Direct comparative data from ISAR-REACT 5 have established a hierarchy favoring prasugrel in patients proceeding to invasive management, although methodological limitations temper definitive conclusions. Beyond agent selection, contemporary practice increasingly emphasizes calibrated therapy: DAPT duration, de-escalation strategies — guided by CYP2C19 genotyping, platelet function testing, or applied empirically — and P2Y₁₂ monotherapy after short DAPT have been validated as approaches that preserve ischaemic protection while reducing bleeding. Special populations, including elderly patients, those with renal impairment, concomitant oral anticoagulation, or cardiogenic shock, require individualized decision-making that exceeds what any single trial provides. Emerging approaches, including subcutaneous selatogrel for patient self-administration and anti-GPVI strategies, signal a shift toward precision antiplatelet therapy. This review synthesizes current evidence across agent pharmacology, duration modulation, special population management, and future directions, framing the transition from potency to precision as the defining trajectory of the field.
