Sacubitril/valsartan reduces serum uric acid concentration, an independent predictor of adverse outcomes in PARADIGM-HF

Mogensen, U. M. et al. (2018) Sacubitril/valsartan reduces serum uric acid concentration, an independent predictor of adverse outcomes in PARADIGM-HF. European Journal of Heart Failure, 20(3), pp. 514-522. (doi: 10.1002/ejhf.1056) (PMID:29193563)

Abstract

Aims: Elevated serum uric acid concentration (SUA) has been associated with an increased risk of cardiovascular disease, but this may be due to unmeasured confounders. We examined the association between SUA and outcomes as well as the effect of sacubitril/valsartan on SUA in patients with heart failure with reduced ejection fraction (HFrEF) in PARADIGM-HF. Methods and results: The association between SUA and the primary composite outcome of cardiovascular death or heart failure (HF) hospitalization, its components, and all-cause mortality was examined using Cox regression analyses among 8213 patients using quintiles (Q1–Q5) of SUA adjusted for baseline prognostic variables including estimated glomerular filtration rate (eGFR), diuretic dose, and log N-terminal pro-brain natriuretic peptide. Change in SUA from baseline over 12 months was also evaluated in each treatment group. Patients in Q5 (SUA ≥8.6 mg/dL) compared with Q1 (<5.4 mg/dL) were younger (62.8 vs. 64.2 years), more often male (88.7% vs. 63.1%), had lower systolic blood pressure (119 vs. 123 mmHg), lower eGFR (57.4 vs. 76.6 mL/min/1.73 m2), and greater diuretic use. Higher SUA was associated with a higher risk of the primary outcome (adjusted hazard ratios) Q5 vs. Q1 = 1.28 [95% confidence intervals (1.09–1.50), P = 0.003], cardiovascular death [1.44 (1.11–1.77), P = 0.001], HF hospitalization [1.37 (1.11–1.70), P = 0.004], and all-cause mortality [1.36 (1.13–1.64), P = 0.001]. Compared with enalapril, sacubitril/valsartan reduced SUA by 0.24 (0.17–0.32) mg/dL over 12 months (P < 0.0001). Sacubitril/valsartan improved outcomes, irrespective of SUA concentration. Conclusion: Serum uric acid concentration was an independent predictor of worse outcomes after multivariable adjustment in patients with HFrEF. Compared with enalapril, sacubitril/valsartan reduced SUA and improved outcomes irrespective of SUA.

• Item Type: Articles
• Additional Information: PARADIGM-HF was funded by Novartis. U.M.M. was supported by a research grant from the Danish Heart Foundation (grant number 16-R107-A6786–22960).
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Kristensen, Mr Soren Lund and Jhund, Professor Pardeep and Mogensen, Dr Ulrik and McMurray, Professor John and Kober, Professor Lars
• Authors: Mogensen, U. M., Køber, L., Jhund, P. S., Desai, A. S., Senni, M., Kristensen, S. L., Dukát, A., Chen, C.-H., Ramires, F., Lefkowitz, M. P., Prescott, M. F., Shi, V. C., Rouleau, J. L., Solomon, S. D., Swedberg, K., Packer, M., and McMurray, J. J.V.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Journal Name: European Journal of Heart Failure
• Publisher: Wiley
• ISSN: 1388-9842
• ISSN (Online): 1879-0844
• Published Online: 30 November 2017
• Copyright Holders: Copyright © 2017 The Authors
• First Published: First published in European Journal of Heart Failure 20
• Publisher Policy: Reproduced under a Creative Commons License