CYP2C19 Phenotype, P2Y ₁₂ Inhibitor Selection, and Clinical Outcomes in Patients on Maintenance Clopidogrel Therapy

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  Figure 1. Outcomes in patients in the maintenance clopidogrel and P2Y12 inhibitor–naïve cohorts. Outline of patient groups (A). Kaplan–Meier survival curves comparing MACE and MAE between maintenance clopidogrel and P2Y12 inhibitor–naïve cohorts (B). The proportion of patients experiencing MACE (C) and MAE (D) during the follow‐up period in the maintenance clopidogrel cohort and P2Y12 inhibitor–naïve cohort. Patients on maintenance clopidogrel had higher MACE and MAE rates compared with P2Y12 inhibitor–naïve cohorts. Kaplan–Meier curves in (B) shows higher MACE rate (left panel) and higher MAE rates (right panel) among patients on maintenance clopidogrel compared with P2Y12 inhibitor–naïve cohorts regardless of P2Y12 inhibitor–CYP2C19 phenotype. Among patients on maintenance clopidogrel who were continued on clopidogrel, there were no significant differences in MACE (C) or MAE (D) event rates between the IM/PM phenotype and the NM/RM/UM phenotype. In contrast, for patients naïve to P2Y12 inhibitors, MACE and MAE rates were significantly higher in those treated with clopidogrel who had the IM/PM phenotype. IM indicates CYP2C19 intermediate metabolizer; MACE, major adverse cardiovascular…

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  Figure 2. MACE and MAE rates in patients who presented with an MI stratified by cohort, CYP2C19 phenotype and P2Y12 inhibitor. The proportion of patients experiencing MACE (A) and MAE (B) events during the follow‐up period in the maintenance clopidogrel cohort and P2Y12 inhibitor–naïve cohort. Kaplan–Meier survival curves (C) for MACE and MAE after stratification into maintenance clopidogrel and P2Y12 inhibitor–naïve cohorts and CYP2C19 phenotype–P2Y12 inhibitor groups. IM indicates intermediate metabolizer; MACE, major adverse cardiovascular events; MAE, major atherothrombotic event; MI, myocardial infarction; NM, normal metabolizer; PM, poor metabolizer; RM, rapid metabolizer; and UM, ultrarapid metabolizer.

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  Figure 3. Unadjusted and adjusted hazard ratios for MACE in the clopidogrel‐treated IM/PM group compared with the clopidogrel‐treated NM/RM/UM group and to the P/T group in the maintenance clopidogrel cohort and P2Y12 inhibitor–naïve cohort. Hazard ratios and 95% CIs are shown. Adjusted hazard ratio was weighted with stabilized inverse probability weights derived from exposure propensity scores. There were 92, 327, and 168 patients in the clopidogrel‐treated IM/PM, clopidogrel‐treated NM/RM/UM and P/T groups, respectively, in the maintenance clopidogrel cohort and 277, 1185, and 1017 patients in the clopidogrel‐treated IM/PM, clopidogrel‐treated NM/RM/UM, and P/T groups, respectively in the P2Y12 inhibitor–naïve cohort. IM indicates intermediate metabolizer; LCL, lower control limit; MACE, major adverse cardiovascular events; MAE, major atherothrombotic event; MI, myocardial infarction; NM, normal metabolizer; OR, odds ratio; PM, poor metabolizer; P/T, prasugrel or ticagrelor; RM, rapid metabolizer; UCL, upper control limit; and UM, ultrarapid metabolizer.