Febuxostat Lowers Blood Pressure in Patients With Hyperuricemia and Hypertension
In patients with hyperuricemia and normal renal function, febuxostat therapy may benefit the BP response to urate-lowering therapy.
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).
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.
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.