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

Ulrik M. Mogensen; Lars Køber; Pardeep S. Jhund; Akshay S. Desai; Michele Senni; Søren L. Kristensen; Andrej Dukát; Chen Huan Chen; Felix Ramires; Martin P. Lefkowitz; Margaret F. Prescott; Victor C. Shi; Jean L. Rouleau; Scott D. Solomon; Karl Swedberg; Milton Packer; John J.V. Mcmurray

doi:10.1002/ejhf.1056

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

Ulrik M. Mogensen, Lars Køber, Pardeep S. Jhund, Akshay S. Desai, Michele Senni, Søren L. Kristensen, Andrej Dukát, Chen Huan Chen, Felix Ramires, Martin P. Lefkowitz, Margaret F. Prescott, Victor C. Shi, Jean L. Rouleau, Scott D. Solomon, Karl Swedberg, Milton Packer, John J.V. Mcmurray^*

^*Corresponding author for this work

Department of Clinical Medicine

19 Citations (Scopus)

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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 12months was also evaluated in each treatment group. Patients in Q5 (SUA ≥8.6mg/dL) compared with Q1 (<5.4mg/dL) were younger (62.8 vs. 64.2years), more often male (88.7% vs. 63.1%), had lower systolic blood pressure (119 vs. 123mmHg), lower eGFR (57.4 vs. 76.6mL/min/1.73m²), 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 12months (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.

Original language	English
Journal	European Journal of Heart Failure
Volume	20
Issue number	3
Pages (from-to)	514-522
ISSN	1388-9842
DOIs	https://doi.org/10.1002/ejhf.1056
Publication status	Published - Mar 2018

Keywords

Angiotensin
Heart failure
Mortality
Neprilysin
Uric acid

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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., & Mcmurray, J. J. V. (2018). Sacubitril/valsartan reduces serum uric acid concentration, an independent predictor of adverse outcomes in PARADIGM-HF. European Journal of Heart Failure, 20(3), 514-522. https://doi.org/10.1002/ejhf.1056

Mogensen, UM, Køber, L, Jhund, PS, Desai, AS, Senni, M, Kristensen, SL, Dukát, A, Chen, CH, Ramires, F, Lefkowitz, MP, Prescott, MF, Shi, VC, Rouleau, JL, Solomon, SD, Swedberg, K, Packer, M & Mcmurray, JJV 2018, 'Sacubitril/valsartan reduces serum uric acid concentration, an independent predictor of adverse outcomes in PARADIGM-HF', European Journal of Heart Failure, vol. 20, no. 3, pp. 514-522. https://doi.org/10.1002/ejhf.1056

@article{646bcfa2fadd433bb9e9e39a550a8efd,

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

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 12months was also evaluated in each treatment group. Patients in Q5 (SUA ≥8.6mg/dL) compared with Q1 (<5.4mg/dL) were younger (62.8 vs. 64.2years), more often male (88.7% vs. 63.1%), had lower systolic blood pressure (119 vs. 123mmHg), lower eGFR (57.4 vs. 76.6mL/min/1.73m2), 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 12months (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.",

keywords = "Angiotensin, Heart failure, Mortality, Neprilysin, Uric acid",

author = "Mogensen, {Ulrik M.} and Lars K{\o}ber and Jhund, {Pardeep S.} and Desai, {Akshay S.} and Michele Senni and Kristensen, {S{\o}ren L.} and Andrej Duk{\'a}t and Chen, {Chen Huan} and Felix Ramires and Lefkowitz, {Martin P.} and Prescott, {Margaret F.} and Shi, {Victor C.} and Rouleau, {Jean L.} and Solomon, {Scott D.} and Karl Swedberg and Milton Packer and Mcmurray, {John J.V.}",

year = "2018",

month = mar,

doi = "10.1002/ejhf.1056",

language = "English",

volume = "20",

pages = "514--522",

journal = "European Journal of Heart Failure, Supplement",

issn = "1567-4215",

publisher = "JohnWiley & Sons Ltd",

number = "3",

}

TY - JOUR

T1 - Sacubitril/valsartan reduces serum uric acid concentration, an independent predictor of adverse outcomes in PARADIGM-HF

AU - Mogensen, Ulrik M.

AU - Køber, Lars

AU - Jhund, Pardeep S.

AU - Desai, Akshay S.

AU - Senni, Michele

AU - Kristensen, Søren L.

AU - Dukát, Andrej

AU - Chen, Chen Huan

AU - Ramires, Felix

AU - Lefkowitz, Martin P.

AU - Prescott, Margaret F.

AU - Shi, Victor C.

AU - Rouleau, Jean L.

AU - Solomon, Scott D.

AU - Swedberg, Karl

AU - Packer, Milton

AU - Mcmurray, John J.V.

PY - 2018/3

Y1 - 2018/3

N2 - 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 12months was also evaluated in each treatment group. Patients in Q5 (SUA ≥8.6mg/dL) compared with Q1 (<5.4mg/dL) were younger (62.8 vs. 64.2years), more often male (88.7% vs. 63.1%), had lower systolic blood pressure (119 vs. 123mmHg), lower eGFR (57.4 vs. 76.6mL/min/1.73m2), 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 12months (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.

AB - 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 12months was also evaluated in each treatment group. Patients in Q5 (SUA ≥8.6mg/dL) compared with Q1 (<5.4mg/dL) were younger (62.8 vs. 64.2years), more often male (88.7% vs. 63.1%), had lower systolic blood pressure (119 vs. 123mmHg), lower eGFR (57.4 vs. 76.6mL/min/1.73m2), 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 12months (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.

KW - Angiotensin

KW - Heart failure

KW - Mortality

KW - Neprilysin

KW - Uric acid

UR - http://www.scopus.com/inward/record.url?scp=85036579608&partnerID=8YFLogxK

U2 - 10.1002/ejhf.1056

DO - 10.1002/ejhf.1056

M3 - Journal article

C2 - 29193563

AN - SCOPUS:85036579608

SN - 1567-4215

VL - 20

SP - 514

EP - 522

JO - European Journal of Heart Failure, Supplement

JF - European Journal of Heart Failure, Supplement

IS - 3

ER -

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

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Keywords

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