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

Selvaraj, S. et al. (2020) Serum uric acid, influence of sacubitril/valsartan, and cardiovascular outcomes in heart failure with preserved ejection fraction: PARAGON-HF. European Journal of Heart Failure, 22(11), pp. 2093-2101. (doi: 10.1002/ejhf.1984) (PMID:32840930)

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Abstract

Aims: To determine the prognostic value of serum uric acid (SUA) on outcomes in heart failure with preserved ejection fraction (HFpEF), and whether sacubitril/valsartan reduces SUA and SUA‐related therapies. Methods and Results: We analyzed 4795 participants from PARAGON‐HF. We related baseline hyperuricemia (using assay definitions) to the primary outcome (CV death and total HF hospitalization). Between baseline and 4 months, we assessed the association between changes in SUA and Kansas City Cardiomyopathy Questionnaire overall summary score (KCCQ‐OSS) and other cardiac biomarkers. We simultaneously adjusted for baseline and time‐updated SUA to determine whether lowering SUA was associated with clinical benefit. Average age was 73 ± 8 years and 52% were women. After multivariable adjustment, hyperuricemia was associated with increased risk for the primary outcome (rate ratio 1.61, 95%CI 1.37, 1.90). The treatment effect of sacubitril/valsartan for the primary endpoint was not significantly modified by hyperuricemia (p‐interaction = 0.14). Sacubitril/valsartan reduced SUA −0.38 mg/dL (95%CI: −0.45, −0.31) compared with valsartan at 4 months, with greater effect in those with elevated SUA vs. normal SUA (−0.51 vs. ‐0.32 mg/dL) (p‐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: SUA independently predicted adverse outcomes in HFpEF. Sacubitril/valsartan reduced SUA and related therapy initiation compared to valsartan. Reducing SUA was associated with improved outcomes.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Cleland, Professor John and McMurray, Professor John and Kober, Professor Lars
Authors: Selvaraj, S., Claggett, B. L., Pfeffer, M. A., Desai, A. S., McCausland, F. R., McGrath, M. M., Anand, I. S., van van Veldhuisen, D. J., Kober, L., Janssens, S., Cleland, J. G.F., Pieske, B., Rouleau, J. L., Zile, M. R., Shi, V. C., Lefkowitz, M. P., McMurray, J. J.V., and Solomon, S. D.
Subjects:R Medicine > R Medicine (General)
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
College of Medical Veterinary and Life Sciences > Institute of Health and Wellbeing > Robertson Centre
Journal Name:European Journal of Heart Failure
Publisher:Wiley
ISSN:1388-9842
ISSN (Online):1879-0844
Published Online:25 August 2020
Copyright Holders:Copyright © 2020 European Society of Cardiology
First Published:First published in European Journal of Heart Failure 22(11): 2093-2101
Publisher Policy:Reproduced in accordance with the publisher copyright policy

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