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 -
