Poor clopidogrel metabolizers with acute coronary syndrome had an increased risk of thrombotic events (OR 1.26), whereas ultra-rapid metabolizers had an increased risk of bleeding events (OR 1.31).
Cohort (n=100)
No
Does the clustering of CYP2C19 and ABCB1 genetic variants predict the risk of major bleeding and thrombotic events in elderly patients with ACS receiving dual antiplatelet therapy with aspirin and clopidogrel?
In elderly ACS patients on clopidogrel and aspirin, combined CYP2C19 and ABCB1 genotyping identifies poor and ultra-rapid metabolizers who are at higher risk for major bleeding and thrombotic events.
Effect estimate: OR 1.26 (95% CI 1.099-1.45)
Absolute Event Rate: 19.6% vs 0%
p-value: p=0.027
OBJECTIVE: The clinical efficacy of clopidogrel in secondary prevention of vascular events is hampered by marked inter-patient variability in drug response, which partially depends on genetic make-up. The aim of this pilot prospective study was to evaluate 12-month cardiovascular outcomes in elderly patients with acute coronary syndrome (ACS) receiving dual antiplatelet therapy (aspirin and clopidogrel) according to the clustering of CYP2C19 and ABCB1 genetic variants. METHODS: Participants were 100 consecutive ACS patients who were genotyped for CYP2C19 (G681A and C-806T) and ABCB1 (C3435T) polymorphisms, which affect clopidogrel metabolism and bioavailability, using PCR-restriction fragment length polymorphism. They were then grouped as poor, extensive and ultra-rapid metabolisers based on the combination of CYP2C19 loss-of-function (CYP2C19*2) and gain-of-function (CYP2C19*17) alleles and ABCB1 alleles. The predictive value of each phenotype for acute vascular events was estimated based on 12-month cardiovascular outcomes. RESULTS: = 5.676; p = 0.048). Logistic regression model, including age, sex, BMI and smoking habit, confirmed the differential risk of major events in low and ultra-rapid metabolisers. CONCLUSIONS: Our findings suggest that ACS patients classified as 'poor or ultra-rapid' metabolisers based on CYP2C19 and ABCB1 genotypes should receive alternative antiplatelet therapies to clopidogrel.
Galeazzi et al. (Sat,) conducted a cohort in Acute Coronary Syndrome (n=100). Clopidogrel and Aspirin vs. Extensive (normal) metabolisers was evaluated on Thrombotic events (poor metabolisers vs others) (OR 1.26, 95% CI 1.099-1.45, p=0.027). Poor clopidogrel metabolizers with acute coronary syndrome had an increased risk of thrombotic events (OR 1.26), whereas ultra-rapid metabolizers had an increased risk of bleeding events (OR 1.31).