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

Stroke. 2020 Jan;51(1):224-231. doi: 10.1161/STROKEAHA.119.026845. Epub 2019 Nov 15.


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/m2, 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/m2). 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.

Keywords: allele; aspirin; body mass index; clopidogrel; overweight.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alleles*
  • Aspirin / administration & dosage*
  • Body Mass Index
  • Clopidogrel / administration & dosage*
  • Cytochrome P-450 CYP2C19 / genetics*
  • Double-Blind Method
  • Female
  • Humans
  • Loss of Function Mutation*
  • Male
  • Middle Aged
  • Obesity* / drug therapy
  • Obesity* / enzymology
  • Obesity* / genetics
  • Risk Factors
  • Stroke* / drug therapy
  • Stroke* / enzymology
  • Stroke* / genetics


  • Clopidogrel
  • CYP2C19 protein, human
  • Cytochrome P-450 CYP2C19
  • Aspirin

Associated data

  • ClinicalTrials.gov/NCT00979589