CYP2C19 and Clopidogrel

Ultrarapid Metabolizer

Clinical Implication

  • Increased CYP2C19 enzyme activity.
  • Higher platelet inhibition, though an association with increased risk of bleeding following PCI has not been observed.

Therapeutic Recommendation

  • Use standard dose of clopidogrel.*

Rapid Metabolizer

Clinical Implication

  • Increased CYP2C19 enzyme activity.
  • Modestly higher platelet inhibition, though an association with increased risk of bleeding following PCI has not been observed.

Therapeutic Recommendation

  • Use standard dose of clopidogrel.*

Normal Metabolizer

Clinical Implication

  • Normal CYP2C19 enzyme activity.
  • Normal response expected.

Therapeutic Recommendation

  • Use standard dose of clopidogrel.

Intermediate Metabolizer

Clinical Implication

  • Decreased CYP2C19 enzyme activity.
  • Reduced activation of clopidogrel and increased risk for major adverse cardiac and cerebrovascular events.

Therapeutic Recommendation

  • Avoid clopidogrel, if there are no contraindications use prasugrel (Effient) 10 mg daily OR use ticagrelor (Brilinta) 90 mg twice daily.*

Poor Metabolizer

Clinical Implication

  • No CYP2C19 enzyme activity.
  • Significantly reduced activation of clopidogrel and increased risk for major adverse cardiac and cerebrovascular events.

Therapeutic Recommendation

  • Avoid clopidogrel, if there are no contraindications use prasugrel (Effient) 10 mg daily OR use ticagrelor (Brilinta) 90 mg twice daily.

Unable to Genotype or Assay Failure

  • The analysis failed to yield an informative result and thus no genotype is reported.

Unknown Phenotype

  • This individual is carrying at least one allele with uncertain/unknown function and the predicted phenotype cannot be determined at this time.

*The majority of evidence supporting recommendations is in the setting of ACS and PCI.  For ultrarapid and rapid metabolizer predicted phenotypes there is limited evidence on clinical outcomes in neurovascular disease. For ultrarapid, rapid, and intermediate metabolizer predicted phenotypes there is limited evidence on clinical outcomes in non-ACS and non-PCI cardiovascular indications.

Reference

  • Lee CR et al. Clin Pharmacol Ther. 2022 Jan 16:10.1002/cpt.2526. PMID: 35034351.

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