Effect of Febuxostat on Ambulatory Blood Pressure in Subjects With Hyperuricemia and Hypertension: A Phase 2 Randomized Placebo-Controlled Study

Abstract

Background: Hyperuricemia is associated with hypertension, with elevated serum uric acid levels postulated to have a causal role in the development of hypertension. Consequently, serum uric acid reduction may help lower blood pressure (BP). A Phase 2, double-blind, placebo-controlled trial was conducted to assess the potential BP-lowering effects of the xanthine oxidase inhibitor febuxostat in subjects with hypertension and hyperuricemia (serum uric acid ≥0.42 mmol/L [≥7.0 mg/dL]).

Methods and results: Subjects (n=121) were randomized 1:1 to febuxostat 80 mg once daily or to placebo. The primary end point was change from baseline to Week 6 in 24-hour mean ambulatory systolic BP (SBP). Additional end points included the following: change from baseline to Week 3 in 24-hour mean SBP and changes from baseline to Weeks 3 and 6 in 24-hour mean ambulatory diastolic BP, serum uric acid, mean daytime and nighttime ambulatory SBP/diastolic BP, and clinic SBP/diastolic BP. For the overall study population, there were no significant differences between febuxostat and placebo for changes from baseline to Weeks 3 or 6 in ambulatory, daytime or nighttime, or clinic SBP or diastolic BP. However, in a preplanned subgroup analysis, there was a significant decrease in SBP from baseline to Week 6 in subjects with normal renal function (estimated glomerular filtration rate ≥90 mL/min) treated with febuxostat versus placebo; least squares mean difference, -6.7; 95% confidence interval -13.3 to -0.0; P=0.049.

Conclusions: This study suggests that febuxostat may lower BP in hyperuricemic patients with hypertension and normal renal function; further studies should be conducted to confirm this finding.

Clinical trial registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01496469.

Keywords: ambulatory blood pressure monitoring; febuxostat; hypertension; hyperuricemia; serum urate; uric acid.

Figure 1

Disposition of subjects. *Reasons for other included subject who did not want to perform study procedures. DBP indicates diastolic blood pressure; PTE, pretreatment adverse event; SBP, systolic blood pressure.

Figure 2

Mean change from baseline in (A) overall, (B) daytime and nighttime, and (C) clinic ambulatory SBP and DBP at Wks 3 and 6. DBP indicates diastolic blood pressure; LS, least squares; SBP, systolic blood pressure.

Figure 3

Mean change from baseline in ambulatory (A) SBP and (B) DBP at Wks 3 and 6 by renal function subgroups. DBP indicates diastolic blood pressure; eGFR, estimated glomerular filtration rate; LS, least squares; SBP, systolic blood pressure.