Clopidogrel is a prodrug requiring CYP2C19 activation. A patient with CYP2C19 poor metabolizer genotype (e.g., carries two loss-of-function alleles) would be BEST switched to which alternative antiplatelet?

• A Higher-dose clopidogrel (150 mg/day)
• B Aspirin monotherapy
• C Dipyridamole
• D Ticagrelor ✓

Explanation

Ticagrelor is a direct-acting (non-prodrug), reversible P2Y12 receptor antagonist that does not require CYP2C19 activation. It achieves predictable platelet inhibition regardless of CYP2C19 genotype. Prasugrel is another alternative that requires CYP3A4/CYP2C19 for activation, but unlike clopidogrel its activation is largely CYP2C19-independent and shows less variability in poor metabolizers. Higher-dose clopidogrel remains inadequate in true poor metabolizers. Current ACCF/AHA guidelines recommend ticagrelor or prasugrel over clopidogrel in ACS patients with poor metabolizer status.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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