CYP2C19 gene variant predicts poor clopidogrel response in PCI patients
MedWire News: Patients receiving high-maintenance dose clopidogrel after percutaneous coronary intervention (PCI) are at increased risk for high post treatment platelet reactivity (HPPR) if they carry CYP2C19 risk alleles, show study results.
"It remains to be evaluated whether carriers of the CYP2C19 variant allele treated with a high-maintenance dose clopidogrel may show poorer cardiovascular outcomes than noncarriers would," say the researchers.
The ACCEL-DOUBLE (Accelerated Platelet Inhibition by a Double Dose of Clopidogrel According to Gene Polymorphism) Study was set up to assess whether genetic variation in the CYP3A5, CYP2C19, and ABCB1 genes influenced the platelet reactivity of 126 patients, aged 61.6 years on average, given high-maintenance dose (150 mg/day) clopidogrel after PCI.
Young-Hoon Jeong (Gyeongsang National University, Jinju, South Korea) and colleagues measured platelet reactivity using standard aggregometry and VerifyNow (Accumetrics Inc, San Diego, California, USA). HPPR was defined as a 5 µmol/l adenosine diphosphate (ADP)-induced maximal platelet reactivity (PRmax) of more than 50%.
The team found that, after at least 1 month of clopidogrel treatment, 5 and 20 µmol/l ADP-induced PRmax were significantly higher in patients who were carriers of the variant (*2 or *3) allele of CYP2C19 (n=80) than in noncarriers (n=46), at 40.7% versus 30.3% (p<0.001) and 54.2% versus 40.5% (p<0.001), respectively.
Additional late platelet reactivity and VerifyNow results confirmed the observed higher platelet reactivity in CYP2C19 variant allele carriers compared with noncarriers.
In total, 27 patients had HPPR. HPPR increased significantly with increasing numbers of CYP2C19 variant alleles, with prevalences of 8.7%, 21.7%, and 50.0%, in those with no, one, and two variant alleles, respectively (p<0.001). General platelet reactivity also increased proportionately to the number of variant alleles present.
The team notes that polymorphisms in CYP3A5 and ABCB1 did not significantly influence platelet reactivity in PCI patients taking clopidogrel.
"These results provide a rationale for further studies to assess whether high-maintenance dose clopidogrel, as compared with noncarriers of the CYP2C19 variant, provides long-term clinical benefits in carriers," write the researchers in the Journal of the American College of Cardiology: Cardiovascular Interventions.
"Subjects with the CYP2C19 polymorphism may benefit more from antiplatelet regimens that do not include clopidogrel, such as use of third-generation thienopyridines, or the addition of a third antiplatelet agent, such as cilostazol," they suggest.
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By Helen Albert