Table 2.
Antiplatelet therapy recommendations based on CYP2C19 phenotype when considering clopidogrel for cardiovascular indications
| CYP2C19 phenotypea |
Implications for phenotypic measures |
Therapeutic recommendation |
Classification of recommendationb - ACS and/or PCIc |
Classification of recommendationb - non-ACS, non-PCI cardiovascular indicationsd |
|---|---|---|---|---|
| CYP2C19 ultrarapid metabolizer | Increased clopidogrel active metabolite formation; lower on-treatment platelet reactivity; no association with higher bleeding risk | If considering clopidogrel, use at standard dose (75 mg/day) | Strong | No recommendation |
| CYP2C19 rapid metabolizer | Normal or increased clopidogrel active metabolite formation; normal or lower on-treatment platelet reactivity; no association with higher bleeding risk | If considering clopidogrel, use at standard dose (75 mg/day) | Strong | No recommendation |
| CYP2C19 normal metabolizer | Normal clopidogrel active metabolite formation; normal on-treatment platelet reactivity | If considering clopidogrel, use at standard dose (75 mg/day) | Strong | Strong |
| CYP2C19 likely intermediate metabolizer | Reduced clopidogrel active metabolite formation; increased on-treatment platelet reactivity; increased risk for adverse cardiac and cerebrovascular events | Avoid standard dose clopidogrel (75 mg) if possible. Use prasugrel or ticagrelor at standard dose if no contraindication. | Stronge | No recommendatione |
| CYP2C19 intermediate metabolizer | Reduced clopidogrel active metabolite formation; increased on-treatment platelet reactivity; increased risk for adverse cardiac and cerebrovascular events | Avoid standard dose (75 mg) clopidogrel if possible. Use prasugrel or ticagrelor at standard dose if no contraindication. | Strong | No recommendation |
| CYP2C19 likely poor metabolizer | Significantly reduced clopidogrel active metabolite formation; increased on-treatment platelet reactivity; increased risk for adverse cardiac and cerebrovascular events | Avoid clopidogrel if possible. Use prasugrel or ticagrelor at standard dose if no contraindication. | Stronge | Moderatee |
| CYP2C19 poor metabolizer | Significantly reduced clopidogrel active metabolite formation; increased on-treatment platelet reactivity; increased risk for adverse cardiac and cerebrovascular events | Avoid clopidogrel if possible. Use prasugrel or ticagrelor at standard dose if no contraindication. | Strong | Moderate |
ACS = acute coronary syndrome; PCI = percutaneous coronary intervention
The online CYP2C19 Allele Frequency Table provides phenotype frequencies for major race/ethnic groups, and the online CYP2C19 Diplotype-Phenotype Table provides a complete list of possible diplotypes and phenotype assignments (8, 9).
Rating scheme described in the Supplemental Material online.
ACS and/or PCI includes patients undergoing PCI for an ACS or non-ACS (elective) indication.
Non-ACS, non-PCI cardiovascular indications include peripheral arterial disease and stable coronary artery disease following a recent myocardial infarction outside the setting of PCI.
The strength of recommendation for “likely” phenotypes are the same as their respective confirmed phenotypes. “Likely” indicates the uncertainty in the phenotype assignment, but it is reasonable to apply the recommendation for the confirmed phenotype to the corresponding “likely” phenotype.