Effect of Febuxostat, a Xanthine Oxidase Inhibitor, on Cardiovascular Risk in Hyperuricemic Patients with Hypertension: A Prospective, Open-label, Pilot Study.
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.
Department of Health Planning Center, Nihon University Hospital, 1-6 Kanda-Surugadai, Chiyoda-ku, Tokyo, 101-8309, Japan. tani.shigemasa@nihon-u.ac.jp.|Division of Cardiology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan. tani.shigemasa@nihon-u.ac.jp.
Shigemasa
S
Tani
Division of Cardiology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan.
Ken
K
Nagao
Division of Cardiology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan.
Atsushi
A
Hirayama
D000368:Aged; D000369:Aged, 80 and over; D002318:Cardiovascular Diseases / Q000175:diagnosis / Q000453:epidemiology / Q000517:prevention & control*; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D000069465:Febuxostat / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D006074:Gout Suppressants / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D006973:Hypertension / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology; D033461:Hyperuricemia / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011446:Prospective Studies; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology; D012307:Risk Factors; D016896:Treatment Outcome; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors*
D004791:Enzyme Inhibitors; D006074:Gout Suppressants; D000069465:Febuxostat; D014969:Xanthine Oxidase