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Impact of impaired glucose tolerance on clopidogrel response in patients with coronary artery disease

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Abstract

Although patients with impaired glucose tolerance (IGT) are at increased atherothrombotic risk, it is unclear how antiplatelet drugs act in patients with IGT. The aim of this study was to investigate the pharmacodynamic response to clopidogrel in patients with IGT and insulin resistance (IR). A 75 g oral glucose tolerance test was performed in 65 coronary artery disease (CAD) patients on aspirin and clopidogrel therapy. Platelet function tests were assessed at 3 time-points by light transmittance aggregometry using ADP (5 and 20 μmol/L) stimuli. 30 patients had IGT and 35 normal glucose tolerance (NGT). Among them, 13 patients showed IR. Following ADP stimuli, patients with IGT showed significantly higher maximal platelet aggregation at each time point than those with NGT patients. This resulted in greater high on-treatment platelet reactivity (HPR) rates at each time point in IGT patients (53.3–36.7 vs. 14.3–11.4 %, p < 0.05). A multivariable logistic regression analysis showed that IGT status was the strongest predictor of HPR (odds ratio 7.54, 95 % CI 1.95–29.1, p = 0.003). Following a glucose load, profiles of platelet reactivity varied according to IR status, with minimal changes over time in patients with IR, while there was a significant reduction in the non-IR patients. In aspirin and clopidogrel-treated patients with CAD, IGT is associated with enhanced platelet reactivity and increased rates of HPR compared with NGT patients. These findings suggest the presence of platelet dysfunction in patients with IGT, which may be attributed to the presence of IR.

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Acknowledgments

The research was supported by a research Grant from Kinki University. We would like to thank José L. Ferreiro for comments on the final draft and Atsuko Murata for technical assistance.

Conflict of interest

Dominick J. Angiolillo: Received payment as an individual for: (a) Consulting fee or honorarium from Bristol Myers Squibb, Sanofi-Aventis, Eli Lilly, Daiichi Sankyo, The Medicines Company, AstraZeneca, Merck, Abbott Vascular and PLx Pharma; (b) Participation in review activities from CeloNova, Johnson & Johnson, St. Jude, and Sunovion. Institutional payments for grants from Bristol Myers Squibb, Sanofi-Aventis, Glaxo Smith Kline, Gilead, Eli Lilly, Daiichi Sankyo, The Medicines Company, and AstraZeneca. Shunichi Miyazaki: research grants from AstraZeneca Co. Ltd, Daiichi-Sankyo Pharmaceutical Co. Ltd, and Shionogi & Co. Ltd. Masafumi Ueno, Kosuke Fujita, Hiroyuki Yamamoto, Tomoyuki Ikeda, Tatsuya Suga, Kenji Yamaji, Shinichiro Ikuta, Kazuhiro Kobuke and Yoshitaka Iwanaga declare that they have no conflict of interest.

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Authors and Affiliations

  1. Division of Cardiology, Department of Internal Medicine, Kinki University Faculty of Medicine, 377-2 Ohnohigashi, Osakasayama, Osaka, 589-8511, Japan

    Masafumi Ueno, Kosuke Fujita, Hiroyuki Yamamoto, Tomoyuki Ikeda, Tatsuya Suga, Kenji Yamaji, Shinichiro Ikuta, Kazuhiro Kobuke, Yoshitaka Iwanaga & Shunichi Miyazaki

  2. University of Florida College of Medicine-Jacksonville, Jacksonville, FL, USA

    Dominick J. Angiolillo

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  1. Masafumi Ueno
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Correspondence to Shunichi Miyazaki.

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Ueno, M., Fujita, K., Yamamoto, H. et al. Impact of impaired glucose tolerance on clopidogrel response in patients with coronary artery disease. J Thromb Thrombolysis 40, 174–181 (2015). https://doi.org/10.1007/s11239-015-1177-7

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