Dapagliflozin reduces uric acid concentration, an independent predictor of adverse outcomes in DAPA-HF

McDowell, K. et al. (2022) Dapagliflozin reduces uric acid concentration, an independent predictor of adverse outcomes in DAPA-HF. European Journal of Heart Failure, 24(6), pp. 1066-1076. (doi: 10.1002/ejhf.2433) (PMID:35064721)

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Abstract

Background: Blood uric acid (UA) levels are frequently elevated in patients with HFrEF, may lead to gout and are associated with worse outcomes. Reduction in UA is desirable in HFrEF and sodium-glucose cotransporter 2 (SGLT2) inhibitors may have this effect. Objectives: To examine the association between UA and outcomes, the effect of dapagliflozin according to baseline UA level, and the effect of dapagliflozin on UA in patients with HFrEF in the DAPA-HF trial. Methods and Results: The association between UA and the primary composite outcome of cardiovascular death or worsening HF, its components, and all-cause mortality was examined using Cox regression analyses among 3119 patients using tertiles of UA, after adjustment for other prognostic variables. Change in UA from baseline over 12 months was also evaluated. Patients in tertile 3 (UA ≥6.8 mg/dL) versus tertile 1 (<5.4 mg/dL) were younger (66.3 ± 10.8 vs 68 ± 10.2 years), more often male (83.1% vs 71.5%), had lower eGFR (58.2 ± 17.4 vs 70.6 ± 18.7 mL/min/1.73m2), and more often treated with diuretics. Higher UA was associated with a greater risk of the primary outcome (adjusted HR tertile 3 vs. tertile 1 = 1.32 [95%CI 1.06, 1.66; P = 0.01). The risk of HF hospitalization and CV death increased by 7% and 6% respectively per 1 mg/dL unit increase of UA. (P = 0.04, 0.07) Spline analysis revealed a linear increase in risk above a cut off UA value of 7.09 mg/dL. Compared with placebo, dapagliflozin reduced UA by 0.84 mg/dL (95% CI -0.93, −0.74) over 12 months (P < 0.001). Dapagliflozin improved outcomes, irrespective of baseline UA concentration. Conclusion: UA remains an independent predictor of worse outcomes in a well-treated contemporary HFrEF population. Compared with placebo, dapagliflozin reduced UA and improved outcomes irrespective of UA concentration.

Item Type:Articles
Additional Information:DAPA-HF was funded by AstraZeneca. JJVM is supported by a British Heart Foundation Centre of Research Excellence Grant RE/18/6/34217.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Docherty, Dr Kieran and McMurray, Professor John and Jhund, Dr Pardeep and McDowell, Dr Kirsty and Sattar, Professor Naveed
Authors: McDowell, K., Welsh, P., Docherty, K. F., Morrow, D. A., Jhund, P. S., De Boer, R. A., O’Meara, E., Inzucchi, S. E., Køber, L., Kosiborod, M. N., Martinez, F. A., Ponikowski, P., Hammarstedt, A., Langkilde, A. M., Sjöstrand, M., Lindholm, D., Solomon, S. D., Sattar, N., Sabatine, M. S., 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:22 January 2022
Copyright Holders:Copyright © 2022 The Authors
First Published:First published in European Journal of Heart Failure 24(6): 1066-1076
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
303944BHF Centre of ExcellenceColin BerryBritish Heart Foundation (BHF)RE/18/6/34217CAMS - Cardiovascular Science