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

Kirsty McDowell; Paul Welsh; Kieran F. Docherty; David A. Morrow; Pardeep S. Jhund; Rudolf A. de Boer; Eileen O'Meara; Silvio E. Inzucchi; Lars Kober; Mikhail N. Kosiborod; Felipe A. Martinez; Piotr Ponikowski; Ann Hammarstedt; Anna Maria Langkilde; Mikaela Sjostrand; Daniel Lindholm; Scott D. Solomon; Naveed Sattar; Marc S. Sabatine; John J. McMurray

doi:10.1002/ejhf.2433

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

Kirsty McDowell, Paul Welsh, Kieran F. Docherty, David A. Morrow, Pardeep S. Jhund, Rudolf A. de Boer, Eileen O'Meara, Silvio E. Inzucchi, Lars Kober, Mikhail N. Kosiborod, Felipe A. Martinez, Piotr Ponikowski, Ann Hammarstedt, Anna Maria Langkilde, Mikaela Sjostrand, Daniel Lindholm, Scott D. Solomon, Naveed Sattar, Marc S. Sabatine, John J. McMurray^*

^*Corresponding author for this work

Cardiovascular Centre (CVC)

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

Aims Blood uric acid (UA) levels are frequently elevated in patients with heart failure and reduced ejection fraction (HFrEF), may lead to gout and are associated with worse outcomes. Reduction in UA is desirable in HFrEF and sodium-glucose cotransporter 2 inhibitors may have this effect. We aimed 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 heart failure, 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 (

Original language	English
Pages (from-to)	1066-1076
Number of pages	11
Journal	European Journal of Heart Failure
Volume	24
Issue number	6
Early online date	22-Feb-2022
DOIs	https://doi.org/10.1002/ejhf.2433
Publication status	Published - Jun-2022

Keywords

Heart failure
Uric acid
Mortality
Sodium-glucose cotransporter 2
Diabetes
CHRONIC HEART-FAILURE
XANTHINE-OXIDASE INHIBITION
POST-HOC ANALYSIS
EJECTION FRACTION
DRUG INTERACTION
GOUT
HYPERURICEMIA
ALLOPURINOL
ASSOCIATION
FUROSEMIDE

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McDowell, K., Welsh, P., Docherty, K. F., Morrow, D. A., Jhund, P. S., de Boer, R. A., O'Meara, E., Inzucchi, S. E., Kober, L., Kosiborod, M. N., Martinez, F. A., Ponikowski, P., Hammarstedt, A., Langkilde, A. M., Sjostrand, M., Lindholm, D., Solomon, S. D., Sattar, N., Sabatine, M. S., & McMurray, J. J. (2022). Dapagliflozin reduces uric acid concentration, an independent predictor of adverse outcomes in DAPA-HF. European Journal of Heart Failure, 24(6), 1066-1076. https://doi.org/10.1002/ejhf.2433

@article{b0de7a0844b64d36bbc2df1e1fde6375,

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

abstract = "Aims Blood uric acid (UA) levels are frequently elevated in patients with heart failure and reduced ejection fraction (HFrEF), may lead to gout and are associated with worse outcomes. Reduction in UA is desirable in HFrEF and sodium-glucose cotransporter 2 inhibitors may have this effect. We aimed 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 heart failure, 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 (",

keywords = "Heart failure, Uric acid, Mortality, Sodium-glucose cotransporter 2, Diabetes, CHRONIC HEART-FAILURE, XANTHINE-OXIDASE INHIBITION, POST-HOC ANALYSIS, EJECTION FRACTION, DRUG INTERACTION, GOUT, HYPERURICEMIA, ALLOPURINOL, ASSOCIATION, FUROSEMIDE",

author = "Kirsty McDowell and Paul Welsh and Docherty, {Kieran F.} and Morrow, {David A.} and Jhund, {Pardeep S.} and {de Boer}, {Rudolf A.} and Eileen O'Meara and Inzucchi, {Silvio E.} and Lars Kober and Kosiborod, {Mikhail N.} and Martinez, {Felipe A.} and Piotr Ponikowski and Ann Hammarstedt and Langkilde, {Anna Maria} and Mikaela Sjostrand and Daniel Lindholm and Solomon, {Scott D.} and Naveed Sattar and Sabatine, {Marc S.} and McMurray, {John J.}",

year = "2022",

month = jun,

doi = "10.1002/ejhf.2433",

language = "English",

volume = "24",

pages = "1066--1076",

journal = "European Journal of Heart Failure",

issn = "1388-9842",

publisher = "Wiley",

number = "6",

}

McDowell, K, Welsh, P, Docherty, KF, Morrow, DA, Jhund, PS, de Boer, RA, O'Meara, E, Inzucchi, SE, Kober, L, Kosiborod, MN, Martinez, FA, Ponikowski, P, Hammarstedt, A, Langkilde, AM, Sjostrand, M, Lindholm, D, Solomon, SD, Sattar, N, Sabatine, MS & McMurray, JJ 2022, 'Dapagliflozin reduces uric acid concentration, an independent predictor of adverse outcomes in DAPA-HF', European Journal of Heart Failure, vol. 24, no. 6, pp. 1066-1076. https://doi.org/10.1002/ejhf.2433

TY - JOUR

T1 - Dapagliflozin reduces uric acid concentration, an independent predictor of adverse outcomes in DAPA-HF

AU - McDowell, Kirsty

AU - Welsh, Paul

AU - Docherty, Kieran F.

AU - Morrow, David A.

AU - Jhund, Pardeep S.

AU - de Boer, Rudolf A.

AU - O'Meara, Eileen

AU - Inzucchi, Silvio E.

AU - Kober, Lars

AU - Kosiborod, Mikhail N.

AU - Martinez, Felipe A.

AU - Ponikowski, Piotr

AU - Hammarstedt, Ann

AU - Langkilde, Anna Maria

AU - Sjostrand, Mikaela

AU - Lindholm, Daniel

AU - Solomon, Scott D.

AU - Sattar, Naveed

AU - Sabatine, Marc S.

AU - McMurray, John J.

PY - 2022/6

Y1 - 2022/6

N2 - Aims Blood uric acid (UA) levels are frequently elevated in patients with heart failure and reduced ejection fraction (HFrEF), may lead to gout and are associated with worse outcomes. Reduction in UA is desirable in HFrEF and sodium-glucose cotransporter 2 inhibitors may have this effect. We aimed 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 heart failure, 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 (

AB - Aims Blood uric acid (UA) levels are frequently elevated in patients with heart failure and reduced ejection fraction (HFrEF), may lead to gout and are associated with worse outcomes. Reduction in UA is desirable in HFrEF and sodium-glucose cotransporter 2 inhibitors may have this effect. We aimed 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 heart failure, 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 (

KW - Heart failure

KW - Uric acid

KW - Mortality

KW - Sodium-glucose cotransporter 2

KW - Diabetes

KW - CHRONIC HEART-FAILURE

KW - XANTHINE-OXIDASE INHIBITION

KW - POST-HOC ANALYSIS

KW - EJECTION FRACTION

KW - DRUG INTERACTION

KW - GOUT

KW - HYPERURICEMIA

KW - ALLOPURINOL

KW - ASSOCIATION

KW - FUROSEMIDE

U2 - 10.1002/ejhf.2433

DO - 10.1002/ejhf.2433

M3 - Article

SN - 1388-9842

VL - 24

SP - 1066

EP - 1076

JO - European Journal of Heart Failure

JF - European Journal of Heart Failure

IS - 6

ER -

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

Abstract

Keywords

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