Abstract 18093: Bleeding Events in Clopidogrel-Treated Patients with STEMI is Associated with a Genetic Risk Score Based on High-Risk Genetic Polymorphisms
Introduction: Gene polymorphisms of ABCB1, CYP2C19, PON1 and P2Y12 may influence pharmacodynamics and clinical events of clopidogrel treatment.
Hypothesis: We assessed the hypothesis that a genetic risk score based on identified high-risk single nucleotide polymorphisms (SNPs) would be associated with bleedings in clopidogrel-treated Chinese STEMI patients after percutaneous coronary intervention (PCI).
Methods: A total of 503 consecutive patients with STEMI who received an uneventful PCI and were exposed to clopidogrel treatment for 12 months, were enrolled in the single-center registry. There were 38 tag SNPs selected from ABCB1, CYP2C19, PON1 and P2Y12 genes, which were detected by the ligase detection reaction. The primary clinical safety endpoint was the incidence of major bleeding events. Major bleeding was quantified according to bleeding academic research consortium definition (BARC) criteria, including type 3 and 5 in the analysis. The follow-up period was 12 months.
Results: Overall, 46 BARC≥3 bleeding events (9.1%) occurred, which included 11 (2.1%) cases of BARC 3b bleedings and 35 (7.0%) cases of BARC 3a bleedings. After adjustment for traditional clinical risk factors, multivariate logistic regression analysis identified SNPs significantly associated with bleedings were ABCB1 (rs1045642, rs2235047, rs7779562), P2Y12 (rs6809699) and CYP2C19*17. A genetic risk score was constructed by summing the number of risk alleles. Bleedings were significantly associated with increased genetic risk score tertile. Patients in the top tertile of the genetic score were estimated to have a 3.268-fold (95%CI=1.198-8.929, p=0.021) increased risk of bleedings compared with those in the bottom tertile. As a continuous variable, the risk score resulted in an OR of 1.326 per unit increase in score (95%CI=1.098-1.601, p=0.003).
Conclusions: This genetic score was significantly associated with bleedings after PCI in our study population.
Author Disclosures: J. Zhang: None. J. Yuan: None. X. Meng: None. X. Tang: None. J. Wang: None. Y. Yao: None.
- © 2014 by American Heart Association, Inc.