Table 3.
Antiplatelet therapy recommendations based on CYP2C19 phenotype when considering clopidogrel for neurovascular indicationsa
| CYP2C19 phenotypeb |
Implications for phenotypic measures |
Therapeutic recommendation | Classification of recommendationc |
Other Considerations |
|---|---|---|---|---|
| CYP2C19 ultrarapid metabolizer | Increased clopidogrel active metabolite formation; lower on-treatment platelet reactivity | No recommendation | No recommendation | |
| CYP2C19 rapid metabolizer | Normal or increased clopidogrel active metabolite formation; normal or lower on-treatment platelet reactivity | No recommendation | 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 | |
| CYP2C19 likely intermediate metabolizer | Reduced clopidogrel active metabolite formation; increased on-treatment platelet reactivity; increased risk for adverse cardiac and cerebrovascular events | Consider an alternative P2Y12 inhibitor at standard dose if clinically indicated and no contraindication. | Moderated | Alternative P2Y12 inhibitors not impacted by CYP2C19 genetic variants include ticagrelor and ticlopidine. Prasugrel is contraindicated in patients with a history of stroke or TIA.e |
| CYP2C19 intermediate metabolizer | Reduced clopidogrel active metabolite formation; increased on-treatment platelet reactivity; increased risk for adverse cardiac and cerebrovascular events | Consider an alternative P2Y12 inhibitor at standard dose if clinically indicated and no contraindication. | Moderate | Alternative P2Y12 inhibitors not impacted by CYP2C19 genetic variants include ticagrelor and ticlopidine. Prasugrel is contraindicated in patients with a history of stroke or TIA. e |
| 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. Consider an alternative P2Y12 inhibitor at standard dose if clinically indicated and no contraindication. | Moderated | Alternative P2Y12 inhibitors not impacted by CYP2C19 genetic variants include ticagrelor and ticlopidine. Prasugrel is contraindicated in patients with a history of stroke or TIA. e |
| 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. Consider an alternative P2Y12 inhibitor at standard dose if clinically indicated and no contraindication. | Moderate | Alternative P2Y12 inhibitors not impacted by CYP2C19 genetic variants include ticagrelor and ticlopidine. Prasugrel is contraindicated in patients with a history of stroke or TIA. e |
Neurovascular disease includes acute ischemic stroke or transient ischemic attack, secondary prevention of stroke, or prevention of thromboembolic events following neurointerventional procedures such as carotid artery stenting and stent-assisted coiling of intracranial aneurysms.
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.
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.
Given limited outcomes data for genotype-guided anti-platelet therapy for neurovascular indications, selection of therapy should depend on individual patient treatment goals and risks for adverse events.