Efficacy of Clopidogrel-Aspirin Therapy for Stroke Does Not Exist in C YP2C19 Loss-of-Function Allele Noncarriers With Overweight/Obesity

Abstract

Background and Purpose— The role of dual-antiplatelet therapy with clopidogrel plus aspirin has been demonstrated to substantially decrease the risk of recurrent stroke among patients with minor stroke and transient ischemic attack. We aimed to determine whether the efficacy of clopidogrel-aspirin therapy among patients with minor stroke / transient ischemic attack was influenced by the stratification of CYP2C19 genotype and body mass index (BMI). Methods— CYP2C19 loss-of-function allele (LoFA) carriers were defined as patients with either LoFA of *2 or *3. Low/normal weight and overweight/obesity was defined as BMI <25 and ≥25 kg/m 2 , respectively. Primary outcome was defined as stroke recurrence at 3 months. Results— In a total of 2933 patients, there were 1726 (58.8%) LoFA carriers and 1275 (43.5%) patients with overweight/obesity (BMI ≥25 kg/m 2 ). Stratified analyses by LoFA carrying status and BMI, hazard ratios (hazard ratios 95% CIs) of the clopidogrel-aspirin therapy for stroke recurrence were 0.90 (0.60–1.36), 0.87 (0.56–1.35), 0.65 (0.39–1.09), and 0.40 (0.22–0.71) among subgroups of LoFA carriers with overweight/obesity, LoFA carriers with low/normal weight, LoFA noncarriers with overweight/obesity, and LoFA noncarriers with low/normal weight, respectively, with P =0.049 for interaction. Conclusions— Efficacy of clopidogrel-aspirin therapy in reducing the risk of stroke recurrence is not present in CYP2C19 LoFA noncarriers with overweight/obesity. Our study suggests that BMI significantly influences the correlation between CYP2C19 genotype and efficacy of clopidogrel-aspirin therapy. Clinical Trial Registration— URL: https://www.clinicaltrials.gov . Unique identifier: NCT00979589.

Impact of Acute Inflammation on Cytochromes P450 Activity Assessed by the Geneva Cocktail

“…In our study, BMI was associated with a significant CYP2C19 activity reduction, which is supported by the literature 35,36 . In fact, the rate of high on‐treatment platelet reactivity to clopidogrel was significantly associated with higher BMI as well as CYP2C19 loss‐of‐function alleles (LoFAs) carrier (*2 or *3) 35 .…”

“…5 In our study, BMI was associated with a significant CYP2C19 activity reduction, which is supported by the literature. 35,36 In fact, the rate of high on-treatment platelet reactivity to clopidogrel was significantly associated with higher BMI as well as CYP2C19 loss-of-function alleles (LoFAs) carrier (*2 or *3). 35 In LoFA noncarriers with overweight/obesity, clopidogrel-aspirin therapy was not efficient in reducing the risk of stroke recurrence as compared with LoFA noncarriers with low/normal weight.…”

“…In fact, the rate of high on‐treatment platelet reactivity to clopidogrel was significantly associated with higher BMI as well as CYP2C19 loss‐of‐function alleles (LoFAs) carrier (*2 or *3) 35 . In LoFA noncarriers with overweight/obesity, clopidogrel‐aspirin therapy was not efficient in reducing the risk of stroke recurrence as compared with LoFA noncarriers with low/normal weight 36 . Again, we expect CYP2C19 activity decrease to be clinically relevant due to the observed phenoconversion in 82% of patients.…”

Development and validation of a prognostic prediction model for antithrombotic-related chronic subdural hematoma in patients with recent acute myocardial infarction

“…Third, BMI significantly influences the association between clopidogrel therapy and the CYP2C19 genotype, and extreme BMI (low and high) predicts the escalation of the bleeding risk (30). However, BMI does not accurately describe body fat accumulation, and surrogate markers of abdominal obesity, such as WHR or waistline circumference, might be more important predictors for unfavorable outcomes in patients with recent AMI with antithrombotic-related CSDH.…”

Analysis of CYP2C19 gene polymorphism and influencing factors of pharmacological response of clopidogrel in patients with cerebral infarction in Zhejiang, China

“…A previous study found that patients with minor stroke/transient ischemic attack with overweight/obesity did not benefit from clopidogrel therapy, and that body mass index (BMI) was a major independent predictor of an insufficient antiplatelet response to clopidogrel ( 29 ). Higher BMI was directly related to hypercholesterol and TGs, and inversely related to HDL cholesterol ( 30 ).…”