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Cytochrome P 450 Polymorphisms And Response To Clopidogrelihab
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Cytochrome P 450 Polymorphisms And Response To Clopidogrelihab


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Cytochrome P 450 Polymorphism 2C19

Cytochrome P 450 Polymorphism 2C19

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  • 1. Cytochrome P-450 polymorphisms and response to clopidogrel Dr. Ihab Suliman
  • 2. Clopidogrel is a prodrug • Clopidogrel is a prodrug that requires biotransformation into its active metabolite by cytochrome P-450 (CYP) enzymes. The genes that encode the CYP enzymes are polymorphic and some alleles may confer reduced biotransformation.
  • 3. • In this study, the investigators studied the relationship between genetic variants in CYP genes, plasma concentrations of active drug metabolite of clopidpogrel and platelet inhibition in 162 healthy subjects (mean age 34 years, 20% women) treated with a 300mg dose of clopidogrel
  • 4. • The association between these genetic variants were compared against cardiovascular outcomes in a separate cohort of 1477 subjects with acute coronary syndromes who were treated with clopidogrel in the Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel–Thrombolysis in Myocardial Infarction (TRITON–TIMI) 38
  • 5. • The investigators found that carriers of at least one CYP2C19 reduced-function allele (34% of the study population) had a relative reduction of 32.4% in plasma exposure to the active metabolite of clopidogrel, as compared with non- carriers (P<0.001). • Carriers also had an absolute reduction in maximal platelet aggregation in response to clopidogrel that was 9% less than that seen in non-carriers (P<0.001).
  • 6. • Among clopidogrel-treated subjects in TRITON–TIMI 38, carriers had a relative increase of 53% in the composite primary efficacy outcome of the risk of death from cardiovascular causes, myocardial infarction, or stroke, as compared with non-carriers (12.1% vs. 8.0%; HR for carriers, 1.53; 95% CI, 1.07 to 2.19; P=0.01)
  • 7. Stent Thrombosis • and an increase by a factor of 3 in the risk of stent thrombosis (2.6% vs. 0.8%; hazard ratio, 3.09; 95% CI, 1.19 to 8.00; P=0.02).
  • 8. Conclusion • The investigators concluded that in patients treated with clopidogrel, carriers of a reduced- function CYP2C19 allele had significantly lower levels of the active metabolite of clopidogrel, diminished platelet inhibition, and a higher rate of major adverse cardiovascular events, including stent thrombosis, than non-carriers.