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Effect of CYP2C19*2 and *3 loss-of-function alleles on platelet reactivity and adverse clinical events in East Asian acute myocardial infarction survivors treated with clopidogrel and aspirin.

Publication ,  Journal Article
Jeong, Y-H; Tantry, US; Kim, I-S; Koh, J-S; Kwon, TJ; Park, Y; Hwang, S-J; Bliden, KP; Kwak, CH; Hwang, J-Y; Gurbel, PA
Published in: Circ Cardiovasc Interv
December 1, 2011

BACKGROUND: As compared with whites, East Asians more often carry the cytochrome P450 (CYP) 2C19 loss-of-function (LOF) allele with the CYP2C19*3 variant. The influence of the CYP2C19 LOF alleles (*2 and *3) on clopidogrel response and clinical outcomes in East Asians with acute myocardial infarction (AMI) has not been reported. We sought to evaluate the effect of the CYP2C19 variants on clopidogrel pharmacodynamics and long-term prognosis in these patients. METHODS AND RESULTS: Patients who survived an AMI (n=266) were enrolled in a single-center registry. Predischarge platelet reactivity was assessed with light transmittance aggregometry and the VerifyNow P2Y12 assay; the CYP2C19*2, *3, *17 and ABCB1 3435C>T variants were determined. The primary clinical end point was the composite of cardiovascular death, nonfatal MI, and ischemic stroke. The median exposure to clopidogrel was 21 months (interquartile range, 13-29). The ABCB1 3435C>T was not related to clopidogrel response or cardiovascular events. Carriage of the CYP2C19 LOF variant allele was relatively high (60.9%, n=162; *2/*17=2, *3/*17=1, *1/*2=96, *1/*3=29, *2/*2=20, and *2/*3=14). Platelet reactivity increased proportionally according to the number of the CYP2C19 LOF alleles. In a multivariate regression analysis, the risk of high on-treatment platelet reactivity (HPR) increased depending on the number of CYP2C19 LOF allele [1 LOF allele; odds ratio (OR), 1.8; 95% confidence interval (CI), 0.8 to 4.2, P=0.152; and 2 LOF alleles; OR, 2.8; 95% CI, 1.2 to 6.5; P=0.016]; platelet reactivity and the rate of HPR did not differ between the CYP2C19*2 versus *3 allele carriage. In addition, cardiovascular event occurrence increased according to the number of the CYP2C19 LOF allele; compared with noncarriers, carriers of 1 [hazard ratio (HR), 3.1; 95% CI, 0.8 to 11.6; P=0.089] and 2 CYP2C19 LOF allele(s) (HR, 10.1; 95% CI, 1.8-58.8; P=0.008) were associated with clinical end point. The clinical impact of the CYP2C19*2 versus *3 allele carriage also did not differ. CONCLUSIONS: Among East Asian patients who survived an AMI, the CYP2C19 LOF allele carriage appears to affect clopidogrel pharmacodynamics and cardiovascular events according to the number of the CYP2C19 LOF allele; the influence of the CYP2C19*2 and *3 alleles on clopidogrel response and long-term outcomes does not differ.

Duke Scholars

Published In

Circ Cardiovasc Interv

DOI

EISSN

1941-7632

Publication Date

December 1, 2011

Volume

4

Issue

6

Start / End Page

585 / 594

Location

United States

Related Subject Headings

  • Treatment Outcome
  • Ticlopidine
  • Prognosis
  • Platelet Aggregation Inhibitors
  • Pharmacogenetics
  • Myocardial Infarction
  • Middle Aged
  • Male
  • Humans
  • Female
 

Citation

APA
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Jeong, Y.-H., Tantry, U. S., Kim, I.-S., Koh, J.-S., Kwon, T. J., Park, Y., … Gurbel, P. A. (2011). Effect of CYP2C19*2 and *3 loss-of-function alleles on platelet reactivity and adverse clinical events in East Asian acute myocardial infarction survivors treated with clopidogrel and aspirin. Circ Cardiovasc Interv, 4(6), 585–594. https://doi.org/10.1161/CIRCINTERVENTIONS.111.962555
Jeong, Young-Hoon, Udaya S. Tantry, In-Suk Kim, Jin-Sin Koh, Tae Jung Kwon, Yongwhi Park, Seok-Jae Hwang, et al. “Effect of CYP2C19*2 and *3 loss-of-function alleles on platelet reactivity and adverse clinical events in East Asian acute myocardial infarction survivors treated with clopidogrel and aspirin.Circ Cardiovasc Interv 4, no. 6 (December 1, 2011): 585–94. https://doi.org/10.1161/CIRCINTERVENTIONS.111.962555.
Jeong, Young-Hoon, et al. “Effect of CYP2C19*2 and *3 loss-of-function alleles on platelet reactivity and adverse clinical events in East Asian acute myocardial infarction survivors treated with clopidogrel and aspirin.Circ Cardiovasc Interv, vol. 4, no. 6, Dec. 2011, pp. 585–94. Pubmed, doi:10.1161/CIRCINTERVENTIONS.111.962555.
Jeong Y-H, Tantry US, Kim I-S, Koh J-S, Kwon TJ, Park Y, Hwang S-J, Bliden KP, Kwak CH, Hwang J-Y, Gurbel PA. Effect of CYP2C19*2 and *3 loss-of-function alleles on platelet reactivity and adverse clinical events in East Asian acute myocardial infarction survivors treated with clopidogrel and aspirin. Circ Cardiovasc Interv. 2011 Dec 1;4(6):585–594.

Published In

Circ Cardiovasc Interv

DOI

EISSN

1941-7632

Publication Date

December 1, 2011

Volume

4

Issue

6

Start / End Page

585 / 594

Location

United States

Related Subject Headings

  • Treatment Outcome
  • Ticlopidine
  • Prognosis
  • Platelet Aggregation Inhibitors
  • Pharmacogenetics
  • Myocardial Infarction
  • Middle Aged
  • Male
  • Humans
  • Female