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Impact of Pancreatic β-Cell Function on Clopidogrel Responsiveness and Outcomes in Chinese Nondiabetic Patients Undergoing Elective Percutaneous Coronary Intervention

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Abstract

Purpose

Insulin resistance and β-cell dysfunction are fundamental defects contributing to type 2 diabetes development. Prior studies indicated that insulin resistance may be correlated with low responsiveness to clopidogrel. This study aimed to investigate the effects of β-cell function on clopidogrel-induced platelet P2Y12 inhibition and the clinical outcomes of nondiabetic patients undergoing elective percutaneous coronary intervention (PCI).

Methods

Patients scheduled to undergo elective PCI and receive clopidogrel in addition to aspirin were recruited for this study. Homeostatic model assessment 2 of β-cell function (HOMA2-β%) was used to classify participants into quartiles. Thromboelastography (TEG) was used to calculate the quantitative platelet inhibition rate to assess clopidogrel-induced antiplatelet reactivity. The clinical outcome was major adverse cardiovascular and cerebrovascular events (MACCEs).

Results

Of the 784 participants evaluated, 21.3% of them (169 of 784) had low responsiveness to clopidogrel. According to multivariate linear regression analysis, the first quartile of HOMA2-β% (19.9–78.1), indicating greater β-cell dysfunction, was independently associated with low responsiveness to clopidogrel compared with the fourth quartile (126.8–326.2) after adjustment for potential covariates [odds ratio 2.140, 95% confidence interval (CI) (1.336 to 3.570), P = 0.038]. In addition, at one year, the first quartile of HOMA2-β% was associated with an increased risk of 1-year MACCE occurrence compared with the fourth quartile [adjusted hazard ratio 4.989, 95% CI (1.571 to 15.845), P = 0.006].

Conclusion

Increased β-cell dysfunction, indicated by a low HOMA2-β%, was associated with low responsiveness to clopidogrel and an increased risk of one-year MACCEs in nondiabetic patients undergoing elective PCI.

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Acknowledgements

We would like to thank American Journal Experts (https://www.aje.com/) for providing English language editing services.

Data availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Funding

The present work was supported by the Beijing Hospital Authority Incubating Program (Code: PX2021028) and a grant from the National Natural Science Foundation of China (Code: 82070301).

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Author notes

  1. Xiliang Zhao and Jin Wang contributed equally to this work.

Authors and Affiliations

  1. Center for Coronary Artery Disease, Division of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, China

    Xiliang Zhao, Quan Li, Yicong Ye & Yong Zeng

  2. Department of Anesthesiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, China

    Jin Wang

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  1. Xiliang Zhao
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Contributions

Xiliang Zhao, Jin Wang, Yong Zeng, and Yicong Ye designed the study. Xiliang Zhao, Jin Wang, and Quan Li contributed to data acquisition. Xiliang Zhao and Jin Wang performed the statistical analysis. Xiliang Zhao, Jin Wang, Quan Li, Yong Zeng, and Yicong Ye contributed to the discussion. Xiliang Zhao and Jin Wang drafted the manuscript. Yicong Ye edited the manuscript. All authors read and approved the final manuscript

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Correspondence to Yong Zeng.

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Zhao, X., Wang, J., Li, Q. et al. Impact of Pancreatic β-Cell Function on Clopidogrel Responsiveness and Outcomes in Chinese Nondiabetic Patients Undergoing Elective Percutaneous Coronary Intervention. Cardiovasc Drugs Ther 37, 487–496 (2023). https://doi.org/10.1007/s10557-021-07272-1

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