Key result
Clopidogrel-aspirin therapy did not significantly reduce stroke recurrence in CYP2C19 loss-of-function allele noncarriers with overweight/obesity (HR 0.65; 95% CI 0.39-1.09; P=0.049 for interaction).
Why the study?
It was unknown whether the efficacy of clopidogrel-aspirin therapy in patients with minor stroke or transient ischemic attack is influenced by CYP2C19 genotype and body mass index.
Does the efficacy of clopidogrel-aspirin therapy in reducing stroke recurrence vary by CYP2C19 genotype and body mass index in patients with minor stroke or transient ischemic attack?
RCT (n=2,933)
Does the efficacy of clopidogrel-aspirin therapy in reducing stroke recurrence vary by CYP2C19 genotype and body mass index in patients with minor stroke or transient ischemic attack?
Hazard Ratio: 0.65 (95% CI 0.39–1.09)
p-value: p=0.049 for interaction
The efficacy of dual antiplatelet therapy with clopidogrel and aspirin in reducing stroke recurrence is significantly attenuated in CYP2C19 loss-of-function allele noncarriers who are overweight or obese.
No benefit from clopidogrel-aspirin in overweight CYP2C19 noncarriers after minor stroke; challenges uniform DAPT use and extends genotype-BMI interaction data.
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.
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Mo et al. (2019) conducted an RCT in minor stroke and transient ischemic attack (n=2,933). clopidogrel-aspirin therapy was evaluated on stroke recurrence at 3 months (HR 0.65, 95% CI 0.39-1.09, p=0.049 for interaction). Clopidogrel-aspirin therapy did not significantly reduce stroke recurrence in CYP2C19 loss-of-function allele noncarriers with overweight/obesity (HR 0.65; 95% CI 0.39-1.09; P=0.049 for interaction).
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