Log in to MyACC
Prediction Rule for Nonresponse to Clopidogrel: ABCD-GENE Score
Study Questions:
What is the utility of a risk score integrating cytochrome P450 2C19 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?
Methods:
The investigators used three prospective and independent studies to: 1) develop a risk score integrating genetic and clinical factors to identify patients with HPR while on clopidogrel, 2) investigate the external validity of the risk score, and 3) define clinical outcomes associated with the risk score in a cohort of patients with myocardial infarction (MI) treated with clopidogrel. A multivariate stepwise logistic regression analysis (entry and exit criteria of p = 0.05 and p = 0.10, respectively) of significant predictors selected by univariate analysis was performed to identify predictors of 30-day HPR and to estimate odds ratios and 95% confidence intervals (CIs).
Results:
A risk score ABCD-GENE (Age, Body Mass Index, Chronic Kidney Disease, Diabetes Mellitus, and Genotyping) was developed incorporating five independent predictors of HPR: four clinical (age >75 years, body mass index >30 kg/m2, chronic kidney disease [glomerular filtration rate <60 ml/min], and diabetes mellitus) and one genetic (cytochrome P450 2C19 loss-of-function alleles). The C-statistics for the score as an integer variable were 0.71 (95% confidence interval [CI], 0.68-0.75) and 0.64 (95% CI, 0.60-0.67) in the pharmacodynamic derivation and validation cohorts, respectively. A cutoff score ≥10 was associated with the best sensitivity and specificity to identify HPR status. The C-statistics for the score were 0.67 (95% CI, 0.64-0.71) for all-cause death and 0.66 (95% CI, 0.63-0.69) for the composite of all-cause death, stroke, or MI at 1 year. Using multiple models for adjustment, the ABCD-GENE score consistently and independently correlated with all-cause death, as well as with the composite of all-cause death, stroke, or MI, both as a continuous variable and by using the cutoff of ≥10. The score did not predict bleeding.
Conclusions:
The authors concluded that the ABCD-GENE score is a simple tool to identify patients with HPR on clopidogrel and who are at increased risk for adverse ischemic events, including mortality, following an acute MI.
Perspective:
The ABCD-GENE score, which encompasses a total of five variables: four clinical (age, body mass index, chronic kidney disease status, and diabetes mellitus) and one genetic (CYP2C19 loss-of-function alleles) showed reasonable discrimination in identifying patients with HPR status and predicted adverse clinical outcomes, including mortality, when applied to a real-world cohort of patients with MI mostly undergoing percutaneous coronary intervention and treated with clopidogrel. These data suggest that in patients with acute coronary syndrome with a high ABCD-GENE score, the use of clopidogrel should be discouraged and treatment with alternative oral P2Y12 inhibitors considered. Prospective evaluation of the ABCD-GENE score is warranted to further define its clinical utility and whether alternative therapies indeed lead to better outcomes.
Clinical Topics: Acute Coronary Syndromes, Diabetes and Cardiometabolic Disease, Invasive Cardiovascular Angiography and Intervention, Prevention, Interventions and ACS
Keywords: Acute Coronary Syndrome, Alleles, Body Mass Index, Diabetes Mellitus, Genetic Testing, Genotype, Metabolic Syndrome, Myocardial Infarction, Myocardial Ischemia, Percutaneous Coronary Intervention, Renal Insufficiency, Chronic, Risk Factors, Secondary Prevention, Stroke
< Back to Listings
