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Published on: April 1, 2019
Relationship between ABCB1 polymorphisms, thromboelastography and risk of bleeding events in clopidogrel-treated
Jia-Hui Zhang1, Xiao-Fang Tang1, Yin Zhang1
1Department of Cardiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 167 Beilishi Road, Xicheng District, Beijing 100037, People's Republic of China.
Insights
Polymorphisms in the ABCB1 gene (rs1045642 and rs7779562) and elevated ADP inhibition measured by thromboelastography (TEG) predict bleeding risk in patients with ST-elevation myocardial infarction (STEMI) treated with clopidogrel.
Area of Science:
- Cardiovascular Medicine
- Pharmacogenomics
- Interventional Cardiology
Background:
- Clopidogrel is a key antiplatelet medication for ST-elevation myocardial infarction (STEMI) patients undergoing percutaneous coronary intervention (PCI).
- Assessing bleeding risk in these patients is crucial for optimizing treatment strategies.
- Genetic variations, particularly in the ABCB1 gene, and platelet reactivity may influence bleeding complications.
Purpose of the Study:
- To investigate the association between ABCB1 gene polymorphisms and bleeding risk.
- To evaluate the predictive value of thromboelastography (TEG) for bleeding events in clopidogrel-treated STEMI patients.
- To identify independent predictors of bleeding complications in this patient population.
Main Methods:
- A cohort of 467 STEMI patients undergoing PCI were analyzed.
- Twenty tag single nucleotide polymorphisms (SNPs) in the ABCB1 gene, along with CYP2C19 variants, were genotyped.
- Platelet reactivity was assessed using TEG, specifically measuring ADP inhibition, with a 12-month follow-up period.
Main Results:
- TEG's ADP inhibition assay demonstrated significant predictive value for Bleeding Academic Research Consortium (BARC) ≥ 3b and ≥ 3 bleedings.
- Multivariable analysis identified high ADP inhibition (>92.5%), carriage of ABCB1 rs1045642, and rs7779562 as independent predictors of BARC ≥ 3 bleedings.
- These findings were validated in an independent cohort of 504 STEMI patients.
Conclusions:
- ABCB1 tag SNPs rs1045642 and rs7779562 are associated with differential bleeding risks in clopidogrel-treated STEMI patients.
- TEG-derived ADP inhibition serves as a valuable predictor of bleeding events.
- These genetic and functional markers can aid in personalized risk stratification for bleeding in STEMI patients.
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 12months.
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 > 93.4%). 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 is associated with higher risk of bleedings while rs7779562 is associated with lower bleeding risk, and ADP inhibition in TEG has a predictive value of bleedings.
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