A patient post-coronary stent placement is on dual antiplatelet therapy with aspirin and ticagrelor. Ticagrelor is preferred over clopidogrel in acute coronary syndrome because ticagrelor:

• A Irreversibly blocks P2Y12 receptors with faster onset than clopidogrel due to its prodrug activation by CYP2C19
• B Directly and reversibly antagonises P2Y12 receptors without requiring hepatic activation, giving consistent platelet inhibition regardless of CYP2C19 genotype ✓
• C Inhibits both P2Y12 and P2Y1 receptors, providing more complete ADP-mediated platelet inhibition
• D Has a longer half-life than clopidogrel, allowing once-daily dosing and improved compliance

Explanation

Ticagrelor is an oral, directly acting, reversible P2Y12 ADP receptor antagonist that does not require hepatic bioactivation. Clopidogrel is a prodrug requiring CYP2C19-mediated conversion, and CYP2C19 poor metabolisers (about 30% of patients, more prevalent in Asian populations) have reduced active metabolite generation, leading to inadequate platelet inhibition. Ticagrelor bypasses this pharmacogenomic variability, providing more consistent and potent antiplatelet effect, which translated to mortality benefit in the PLATO trial. Ticagrelor is given twice daily (not once daily) due to its shorter half-life (~12 hours) than the irreversible platelet blockade duration of clopidogrel.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

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Written and medically reviewed by the StethoPrep medical team.