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Clopidogrel Resistance CYP2C19 — EECC MCQ

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ModerateCardiac PharmacologyClopidogrel Resistance CYP2C19EECC

A 65-year-old man on clopidogrel 75 mg after PCI asks about the concept of 'clopidogrel resistance.' His cardiologist considers platelet function testing. What is the prevalence and clinical significance of clopidogrel resistance?

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Correct answer: C — Variable CYP2C19-mediated response with higher thrombotic risk

Clopidogrel is a prodrug requiring hepatic conversion to its active metabolite primarily by CYP2C19. CYP2C19 loss-of-function (LOF) polymorphisms (*2, *3 alleles) reduce conversion, resulting in 'clopidogrel resistance' (high on-treatment platelet reactivity, HTPR): prevalence ~15-40% (higher in Asian populations — CYP2C19*2 carrier frequency ~25-30% vs ~15-20% in Europeans). Clinical significance: increased stent thrombosis, MI, and CV death in poor metabolisers. Options: (1) genotype-guided therapy (CYP2C19 testing) — if LOF carrier: switch to ticagrelor or prasugrel (not CYP2C19-dependent); if normal metaboliser: continue clopidogrel; (2) phenotypic platelet function testing (VerifyNow, VASP) to identify HTPR. The 2023 ESC ACS Guidelines: routine platelet function/genetic testing is not recommended (Class III) but may be considered in specific scenarios (recurrent ischaemic events, stent thrombosis, high-risk PCI).

Reference: ESC (2023): ACS Guidelines: https://bnf.nice.org.uk/