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

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 condu...

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Autores principales: Gunawardhana, Lhanoo, McLean, Lachy, Punzi, Henry A., Hunt, Barbara, Palmer, Robert N., Whelton, Andrew, Feig, Daniel I.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5721765/
https://www.ncbi.nlm.nih.gov/pubmed/29102979
http://dx.doi.org/10.1161/JAHA.117.006683
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author Gunawardhana, Lhanoo
McLean, Lachy
Punzi, Henry A.
Hunt, Barbara
Palmer, Robert N.
Whelton, Andrew
Feig, Daniel I.
author_facet Gunawardhana, Lhanoo
McLean, Lachy
Punzi, Henry A.
Hunt, Barbara
Palmer, Robert N.
Whelton, Andrew
Feig, Daniel I.
author_sort Gunawardhana, Lhanoo
collection PubMed
description 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.
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spelling pubmed-57217652017-12-12 Effect of Febuxostat on Ambulatory Blood Pressure in Subjects With Hyperuricemia and Hypertension: A Phase 2 Randomized Placebo‐Controlled Study Gunawardhana, Lhanoo McLean, Lachy Punzi, Henry A. Hunt, Barbara Palmer, Robert N. Whelton, Andrew Feig, Daniel I. J Am Heart Assoc Original Research 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. John Wiley and Sons Inc. 2017-11-04 /pmc/articles/PMC5721765/ /pubmed/29102979 http://dx.doi.org/10.1161/JAHA.117.006683 Text en © 2017 The Authors and Takeda Pharmaceuticals. Published on behalf of the American Heart Association, Inc., by Wiley. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial (http://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Original Research
Gunawardhana, Lhanoo
McLean, Lachy
Punzi, Henry A.
Hunt, Barbara
Palmer, Robert N.
Whelton, Andrew
Feig, Daniel I.
Effect of Febuxostat on Ambulatory Blood Pressure in Subjects With Hyperuricemia and Hypertension: A Phase 2 Randomized Placebo‐Controlled Study
title Effect of Febuxostat on Ambulatory Blood Pressure in Subjects With Hyperuricemia and Hypertension: A Phase 2 Randomized Placebo‐Controlled Study
title_full Effect of Febuxostat on Ambulatory Blood Pressure in Subjects With Hyperuricemia and Hypertension: A Phase 2 Randomized Placebo‐Controlled Study
title_fullStr Effect of Febuxostat on Ambulatory Blood Pressure in Subjects With Hyperuricemia and Hypertension: A Phase 2 Randomized Placebo‐Controlled Study
title_full_unstemmed Effect of Febuxostat on Ambulatory Blood Pressure in Subjects With Hyperuricemia and Hypertension: A Phase 2 Randomized Placebo‐Controlled Study
title_short Effect of Febuxostat on Ambulatory Blood Pressure in Subjects With Hyperuricemia and Hypertension: A Phase 2 Randomized Placebo‐Controlled Study
title_sort effect of febuxostat on ambulatory blood pressure in subjects with hyperuricemia and hypertension: a phase 2 randomized placebo‐controlled study
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5721765/
https://www.ncbi.nlm.nih.gov/pubmed/29102979
http://dx.doi.org/10.1161/JAHA.117.006683
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