Data Management And Sharing System of China National Clinical Research Center for Neurological Diseases
Application of Age, Body Mass Index, Chronic Kidney Disease, Diabetes, and Genotyping Score for Efficacy of Clopidogrel: Secondary Analysis of the CHANCE Trial
First author：Liye Dai
Corresponding author：Yongjun Wang
essential_information
2021-10-20
Published articles
Journal：stroke
Publication type: Original Contributions
IF(IF): 7.914
PMID: 34666508 Link To Pubmed Full text Download
Background And Purpose
Although carriers of loss-of-function alleles of the CYP2C19 enzyme have reduced clopidogrel metabolism leading to increased rates of clopidogrel nonresponsiveness and thrombotic complications, this explains only a fraction of the pharmacodynamic response to clopidogrel, and a number of clinical factors have also been shown to have contributing roles. The ABCD-gene (Age, Body Mass Index, Chronic Kidney Disease, Diabetes Mellitus, and Genotyping) is a risk score integrating CYP2C19 loss-of-function genotypes with clinical risk factors influencing clopidogrel response that would allow the identification with more precision of subjects at risk for high platelet reactivity (HPR) and adverse clinical outcomes. The ABCD-GENE was developed incorporating 5 independent predictors of HPR: 4 clinical (age >75 years, body mass index >30 kg/m2,chronic kidney disease [glomerular filtration rate<60ml/min], and diabetes mellitus) and 1 genetic (cytochrome P4502C19 loss-of-function alleles). Derivation, Validation, and Prognostic Utility of the ABCD-gene score has been recently published in JACC Cardiovasc Interv. We aimed to compare the efficacy of clopidogrel–aspirin therapy with that of aspirin therapy in MS/TIA patients stratified by the ABCD-gene score.
Method
CYP2C19 loss-of-function allele (LoFA) carriers were defined as patients with either LoFA of *2 or *3. Participants were scored on the basis of the sum of weighted predictors present in the ABCD-gene score. Using the cutoff with the best sensitivity and specificity(≥10),patients were stratified by ABCD-GENE scores ≥10 and <10. Primary outcome was defined as stroke recurrence at 3 months.
Conclusion
Among Chinese minor stroke/transient ischemic attack population, the efficacy of clopidogrel-aspirin therapy was decreased in patients with higher ABCD-GENE score. Our study suggests that CYP2C19 genotypes and clinical risk factors can be integrated by ABCD-GENE score to estimate the efficacy of clopidogrel-aspirin therapy.
Main results
Among a total of 2923 patients with minor stroke/transient ischemic attack, there were 2273 (77.76%) with ABCDGENE score <10 and 650 (22.24%) patients with ABCD-GENE score ≥10. Compared with the aspirin alone, hazard ratios (95% CIs) of the clopidogrel-aspirin therapy for stroke recurrence were 0.70 (0.54–0.91) and 0.76 (0.46–1.24), among patients of ABCD-GENE scores <10 and ABCD-GENE scores ≥10, respectively. Stratified analyses by ABCD-GENE score 0 to 5, 6 to 24, and >24, hazard ratios of the clopidogrel-aspirin therapy for stroke recurrence were 0.57 (95% CI, 0.38–0.85), 0.78 (0.58–1.06), and 1.20 (0.44–3.28) (P value for trend=0.0052).