Serum uric acid, influence of sacubitril-valsartan, and cardiovascular outcomes in heart failure with preserved ejection fraction: PARAGON-HF.

Journal Article (Journal Article)

AIMS: This study aimed to determine the prognostic value of serum uric acid (SUA) on outcomes in heart failure (HF) with preserved ejection fraction (HFpEF), and whether sacubitril-valsartan reduces SUA and use of SUA-related therapies. METHODS AND RESULTS: We analysed 4795 participants from the Prospective Comparison of ARNI [angiotensin receptor-neprilysin inhibitor] with ARB [angiotensin-receptor blockers] Global Outcomes in HF with Preserved Ejection Fraction (PARAGON-HF) trial. We related baseline hyperuricaemia (using age and gender adjusted assay definitions) to the primary outcome [cardiovascular (CV) death and total HF hospitalizations]. We assessed the associations between changes in SUA and Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-OSS) and other cardiac biomarkers from baseline to 4 months. We simultaneously adjusted for baseline and time-updated SUA to determine whether lowering SUA was associated with clinical benefit. The mean (± standard deviation) age of patients was 73 ± 8 years and 52% were women. After multivariable adjustment, hyperuricaemia was associated with increased risk for the primary outcome [rate ratio 1.61, 95% confidence interval (CI) 1.37-1.90]. The treatment effect of sacubitril-valsartan for the primary endpoint was not significantly modified by hyperuricaemia (P-value for interaction = 0.14). Sacubitril-valsartan reduced SUA by 0.38 mg/dL (95% CI 0.31-0.45) compared with valsartan at 4 months, with greater effect in those with elevated SUA vs. normal SUA (-0.51 mg/dL vs. -0.32 mg/dL) (P-value for interaction = 0.031). Sacubitril-valsartan reduced the odds of initiating SUA-related treatments by 32% during follow-up (P < 0.001). After multivariable adjustment, change in SUA was inversely associated with change in KCCQ-OSS and directly associated with high-sensitivity troponin T (P < 0.05). Time-updated SUA was a stronger predictor of adverse outcomes than baseline SUA. CONCLUSIONS: Serum uric acid independently predicted adverse outcomes in HFpEF. Sacubitril-valsartan reduced SUA and the initiation of related therapy compared with valsartan. Reductions in SUA were associated with improved outcomes.

Full Text

Duke Authors

Cited Authors

  • Selvaraj, S; Claggett, BL; Pfeffer, MA; Desai, AS; Mc Causland, FR; McGrath, MM; Anand, IS; van Veldhuisen, DJ; Kober, L; Janssens, S; Cleland, JGF; Pieske, B; Rouleau, JL; Zile, MR; Shi, VC; Lefkowitz, MP; McMurray, JJV; Solomon, SD

Published Date

  • November 2020

Published In

Volume / Issue

  • 22 / 11

Start / End Page

  • 2093 - 2101

PubMed ID

  • 32840930

Electronic International Standard Serial Number (EISSN)

  • 1879-0844

Digital Object Identifier (DOI)

  • 10.1002/ejhf.1984


  • eng

Conference Location

  • England