Febuxostat Lowers Blood Pressure in Patients With Hyperuricemia and Hypertension

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Febuxostat may lower blood pressure in patients with hyperuricemia, hypertension, and normal renal function.

Use of the xanthine oxidase inhibitor febuxostat may reduce 24-hour ambulatory systolic blood pressure (SBP) in patients with hypertension, hyperuricemia, and normal renal function, according to the results of a recent phase 2 randomized placebo-controlled study (ClinicalTrials.gov Identifier: NCT01496469) published in the Journal of the American Heart Association.

A total of 121 patients with hypertension and hyperuricemia (serum uric acid ≥0.42 mmol/L) were randomly assigned in a 1:1 ratio to receive febuxostat 80 mg once daily or placebo. Eligible participants were age ≥18 and were taking ≤2 baseline BP medications. The primary efficacy end point was change from baseline to 6 weeks in 24-hour mean ambulatory SBP. Secondary efficacy endpoints included change in 24-hour mean ambulatory diastolic blood pressure (DBP) and serum uric acid from baseline to 6 weeks. Additional end points included change in 24-hour mean ambulatory SBP/DBP from baseline to 3 weeks, as well as change in mean daytime and nighttime ambulatory SBP/DBP and clinic SBP/DBP from baseline to 3 and 6 weeks.

In the overall study population, no significant differences were reported between febuxostat and placebo in change from baseline to 3 or 6 weeks in ambulatory, daytime or nighttime, or clinic SBP/DBP. In a preplanned subgroup analysis, however, a small, significant decrease in SBP from baseline to 6 weeks was reported in participants with normal renal function (estimated glomerular filtration rate ≥90 mL/min) treated with febuxostat vs placebo (least square mean difference, –6.7; 95% CI, –13.3 to –0.0; P =.049). 

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The investigators concluded that in hyperurecemic patients with normal renal function, febuxostat therapy might exhibit additional benefits related to the blood pressure response to urate-lowering therapy. The agent appeared to have fewer BP-lowering effects in patients with impaired renal function, however, possibly due to the association of hypertension and uric acid with vascular damage. Additional studies are warranted to confirm these findings.

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Gunawardhana L, McLean L, Punzi HA, et al.  Effect of febuxostat on ambulatory blood pressure in subjects with hyperuricemia and hypertension: a phase 2 randomized placebo-controlled study. J Am Heart Assoc. 2017;6(11):e006683.