Abstract 17968: Do Use of Proton Pump Inhibitor (PPI) and CYP2C19 Polymorphism Have the Same Degree of Impact on Cardiovascular Outcomes in Patients with Acute Coronary Syndrome (ACS) ?
Background: CYP2C19 polymorphism or use of a proton pump inhibitor (PPI) may be associated with wide interindividual variability in platelet response to clopidogrel. However, it remains unknown about the relation between CYP2C19 *2, or *3 polymorphism and use of a PPI for clinical outcomes in Asians. The aim was to examine which factor, CYP2C19 genotype or use of a PPI, is stronger to affect the recurrence of cardiovascular events in ACS patients receiving dual antiplatelet therapy with aspirin and clopidogrel.
Methods: We examined CYP2C19 genotype and platelet aggregation induced by adenosine diphosphate using light transmittance aggregometry in 191 coronary artery disease patients treated with stenting (ACS; n=71, male 50, age 69 yrs: stable angina (SA; n=120, male 83, age 68 yrs).
Results: In ACS, the distribution of CYP2C19 genotype was 44, 39, and 17 % in the wild-type homozygotes (CYP2C19*1/*1), in the *2, or *3 heterozygotes carrying one loss-of-function allele (*1/*2, *1/*3), and in the *2, or *3 homozygotes carrying two loss-of-function alleles (*2/*2, *2/*3, *3/*3), respectively. The platelet aggregation decreased significantly in the wild-type homozygotes, subsequently in the *2, *3 heterozygotes, and was not well inhibited in the *2, *3 homozygotes (3759+/−1563, 4268+/−1761, and 5118+/−1224 AU*min, respectively). However, patients with the *2, *3 homozygotes and heterozygotes showed the decreased platelet reactivities at > 7 days after clopidogrel loading compared with those at < 7 days. The occurrence of cardiovascular events were more increased in the *2, *3 homozygotes and heterozygotes than in the CYP2C19 wild-type homozygotes (*1/*1). While there were no differences in the value of platelet reactivity and clinical outcome between PPI use and no-PPI use. Likewise, the CYP2C19 distribution in SA was the same as that in ACS, however, there was significant difference in the recurrence of cardiovascular events according to CYP2C19 genotype between ACS and SA patients.
Conclusions: The risk of cardiovascular events depends on CYP2C19 polymorphism regardless of whether PPI use or not, and the impact of CYP2C19 genotype on platelet reactivity and cardiovascular event is stronger compared with a use of PPIs in Asian patients with ACS.
- © 2010 by American Heart Association, Inc.