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Short-Term Impact of Low-Dose Atorvastatin on Serum Proprotein Convertase Subtilisin/Kexin Type 9

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Abstract

Background and Objective

Several small studies have found that moderate- to high-dose statins (HMG-CoA reductase inhibitors) could increase the serum proprotein convertase subtilisin/kexin type 9 (PCSK9) level. However, little is known regarding the short-term, dose-dependent effects of low-dose atorvastatin and the rapid effects of a single dose of atorvastatin on PCSK9. The objective of this study was to investigate the short-term impact of low-dose atorvastatin on PCSK9 in humans.

Methods

In this randomized study, data from 66 subjects were analyzed. In protocol I, 32 patients were randomized to atorvastatin 10 mg/day (n = 19) or 20 mg/day (n = 13) and eight healthy subjects without therapy were controls for 8 weeks. Serum PCSK9 and lipid profile were determined at day 0, week 4, and week 8. In protocol II, 26 patients were randomized to a single dose of atorvastatin 10 mg (n = 11) or 80 mg (n = 15), and serum levels of PCSK9 were measured at 24 h after treatment.

Results

Atorvastatin 10 mg/day decreased low-density lipoprotein cholesterol (LDL-C) by 32 % at 4 weeks and by 33 % at 8 weeks, and atorvastatin 20 mg/day resulted in reduction of LDL-C by 41 % at 4 weeks and by 38 % at 8 weeks. Atorvastatin 10 mg/day slightly increased serum PCSK9 by 5–7 % but without a significant difference, while atorvastatin 20 mg/day significantly increased serum PCSK9 by 30 % at 4 weeks and by 35 % at 8 weeks (p = 0.009 and p = 0.002, respectively). In addition, 24 h after a single dose, atorvastatin 10 mg significantly increased serum PCSK9 by 13 % and atorvastatin 80 mg by 27 % (p = 0.042 and p = 0.001, respectively).

Conclusion

The short-term impact of low-dose atorvastatin on PCSK9 was time and dose dependent, with a rapid increase in PCSK9 levels being observed within 24 h of dosing.

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Acknowledgments

The authors have no potential conflicts of interest that are directly relevant to the content of the study.

This work is partly supported by the National Natural Scientific Foundation (81070171, 81241121), Specialized Research Fund for the Doctoral Program of Higher Education of China (20111106110013), and Fund of Capital Special Foundation of Clinical Application Research (Z121107001012015) awarded to Dr. Jian-Jun Li, MD, PhD, and also partly supported by the Fu Wai Hospital Youth Fund (No. 2010-F02) awarded to Dr. Yuan-Lin Guo, MD, PhD. The financial supporters had no role in the design, conduct, analysis, or reporting of this study.

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Authors and Affiliations

  1. Division of Dyslipidemia, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, Beilishi Road 167, Beijing, 100037, China

    Yuan-Lin Guo, Jun Liu, Rui-Xia Xu, Cheng-Gang Zhu, Na-Qiong Wu, Li-Xin Jiang & Jian-Jun Li

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  1. Yuan-Lin Guo
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  2. Jun Liu
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  3. Rui-Xia Xu
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  4. Cheng-Gang Zhu
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  7. Jian-Jun Li
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Correspondence to Jian-Jun Li.

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Guo, YL., Liu, J., Xu, RX. et al. Short-Term Impact of Low-Dose Atorvastatin on Serum Proprotein Convertase Subtilisin/Kexin Type 9. Clin Drug Investig 33, 877–883 (2013). https://doi.org/10.1007/s40261-013-0129-2

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  • DOI: https://doi.org/10.1007/s40261-013-0129-2

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