Relationship between ABCB1 polymorphisms, thromboelastography and risk of bleeding events in clopidogrel-treated patients with ST-elevation myocardial infarction

Abstract

Introduction: This study sought to investigate the relationship of polymorphisms in ABCB1 and the predictive value of thromboelastography (TEG) on bleeding risk in clopidogrel-treated patients with ST-elevation myocardial infarction (STEMI). Methods: 467 consecutive patients with STEMI undergoing percutaneous coronary intervention (PCI) were enrolled. Twenty tag single nucleotide polymorphisms (SNPs) selected from ABCB1 gene and CYP2C19∗2, ∗3, ∗17 were detected by the ligase detection reaction. Platelet reactivity was assessed by TEG. The follow-up period was 12 months. Results: By receiver operating characteristic curve analysis, the TEG platelet mapping assay value of ADP inhibition had the best predictive value of bleeding academic research consortium definition (BARC) ≥3b bleedings, yielding an area under the curve (AUC) of 0.707 (95% CI 0.662-0.749, p = 0.009; cut-off value N93.4%). ADP inhibition can also predict BARC ≥ 3 bleedings with an AUC of 0.594 (95% CI 0.546-0.640, p = 0.05; cut-off value >92.5%). After adjustment for established risk factors of bleeding including the gain of function CYP2C19∗17 allele, age, female gender, renal function, the multivariable logistic regression model demonstrated that ADP inhibition > 92.5% (OR 2.247, 95%CI 1.082-4.665, P = 0.03), carriage of rs1045642 (OR 2.943, 95%CI 1.195-7.247, P = 0.019) and rs7779562 (OR 0.453, 95%CI 0.219-0.936, P = 0.032) were independent predictors of BARC ≥ 3 bleedings. These associations were validated in a second cohort of 504 STEMI patients. Conclusions: In STEMI patients treated with clopidogrel after PCI, the ABCB1 tag SNP rs1045642 isassociated with higher risk of bleedings while rs7779562 is associated with lower bleeding risk, and ADP inhibition in TEG has a predictive value of bleedings.