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Effect of Febuxostat, a Xanthine Oxidase Inhibitor, on Cardiovascular Risk in Hyperuricemic Patients with Hypertension: A Prospective, Open-label, Pilot Study

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Abstract

Background and Objective

There is growing evidence of an association between high uric acid (UA) levels and cardiovascular disease (CVD). We hypothesized that febuxostat, a xanthine oxidase inhibitor, may be associated with suppressing the renin-angiotensin-aldosterone system (RAAS) and improving renal function in hyperurecemic patients with hypertension.

Methods

We conducted a 6-month prospective study in which we randomized hypertensive hyperuricemic patients to either a febuxostat group (n = 30) or a control group (n = 30). The dose of febuxostat was adjusted to maintain the serum UA level at <6.0 mg/dL.

Results

In the febuxostat group, the plasma renin activity (PRA), plasma aldosterone concentration (PAC), and serum UA level significantly decreased by 33 % (p = 0.0012), 14 % (p = 0.001), and 29 % (p < 0.0001), respectively. The estimated glomerular filtration rate (eGFR) significantly increased by 5.5 % (p = 0.001). Similar changes were not observed in the control group. Furthermore, a significant correlation was observed between the percent changes in the serum UA levels and the percent changes in the PRA (r = 0.277, p = 0.033), PAC (r = 0.310, p = 0.016), serum blood urea nitrogen levels (r = 0.434, p = 0.0005), serum creatinine levels (r = 0.413, p = 0.002), and eGFR (r = −0.474, p = 0.0001).

Conclusions

These results support the hypothesis that febuxostat might not only reduce serum UA levels but also suppress RAAS and improve renal function in hyperuricemic patients with hypertension, possibly leading to prevention of CVD.

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Acknowledgments

We thank all patients and investigators involved in these studies.

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Authors and Affiliations

  1. Department of Health Planning Center, Nihon University Hospital, 1-6 Kanda-Surugadai, Chiyoda-ku, Tokyo, 101-8309, Japan

    Shigemasa Tani

  2. Division of Cardiology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan

    Shigemasa Tani, Ken Nagao & Atsushi Hirayama

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  1. Shigemasa Tani
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  2. Ken Nagao
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Correspondence to Shigemasa Tani.

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The authors declare that they have no conflict of interest.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

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All patients gave their written informed consent prior to the start of each study.

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Tani, S., Nagao, K. & Hirayama, A. Effect of Febuxostat, a Xanthine Oxidase Inhibitor, on Cardiovascular Risk in Hyperuricemic Patients with Hypertension: A Prospective, Open-label, Pilot Study. Clin Drug Investig 35, 823–831 (2015). https://doi.org/10.1007/s40261-015-0349-8

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  • DOI: https://doi.org/10.1007/s40261-015-0349-8

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