Tailored Thienopyridine Therapy: No Urgency for CYP 2C19 Genotyping

Between 20% and 50% of cardiovascular patients treated with clopidogrel, an anti‐P2Y12 drug, display high on‐treatment platelet reactivity ( HTPR ) and are not adequately protected from major adverse cardiovascular events ( MACE ). Despite a minor influence of the CYP 2C19*2 genetic variant on the pharmacodynamic response to clopidogrel (5% to 12%) and a limited or absent value for predicting stent thrombosis and MACE , this latter polymorphism is currently considered an important candidate to tailor anti‐P2Y12 therapy during percutaneous coronary intervention. Seven studies have examined the value of CYP 2C19*2 for predicting HTPR in comparison to a specific pharmacodynamic assay ( VASP assay). Overall, the summarized sensitivity of the CYP 2C19*2 genotype for predicting HTPR was 37.6% (95% CI : 32.2 to 43.3%), yielding a negative likelihood ratio of only 0.77 (95% CI : 0.68 to 0.86) which confirms its limited value as a routine clinical aid. A tailored anti‐P2Y12 treatment strategy restricted to CYP 2C19*2 carriers may be of some help, but this restrictive approach leaves out noncarriers with HTPR . As for platelet function testing, there is currently no convincing data to support that using CYP 2C19*2 genotyping as a tailored anti‐P2Y12 treatment would be an effective strategy and there is no urgency for CYP 2C19 genotyping in clinical practice. Strategies incorporating genotyping, phenotyping, and clinical data in a stratified and sequential approach may be more promising.