The pharmacogenomic test most relevant to deciding clopidogrel dose adequacy in a patient with coronary artery disease is genotyping for:

• A CYP2C9*2/*3 alleles (reduced warfarin metabolism)
• B VKORC1 gene variants (warfarin sensitivity)
• C CYP2D6 poor metabolizer status (reduced codeine analgesia)
• D CYP2C19*2/*3 (loss-of-function) alleles (reduced clopidogrel activation) ✓

Explanation

Clopidogrel is a prodrug requiring hepatic activation to its active thiol metabolite via a two-step CYP2C19-dependent oxidative process. CYP2C19*2 and *2/*3 loss-of-function alleles result in reduced or absent CYP2C19 activity, producing inadequate active metabolite levels and high platelet reactivity on clopidogrel. Poor metabolisers have a significantly increased risk of MACE (major adverse cardiovascular events) after coronary stent implantation. The FDA black-box warning on clopidogrel recommends considering alternative antiplatelet therapy (prasugrel or ticagrelor, which do not require CYP2C19 activation) in known poor metabolisers. CYP2C9 and VKORC1 are relevant to warfarin, not clopidogrel.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.