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Cardiology Xagena

Sacubitril and Valsartan combination reduces serum uric acid concentration, an independent predictor of adverse outcomes


Elevated serum uric acid concentration ( SUA ) has been associated with an increased risk of cardiovascular disease, but this may be due to unmeasured confounders.

Researchers have examined the association between uric acid concentration and outcomes as well as the effect of Sacubitril and Valsartan combination on uric acid concentration in patients with heart failure with reduced ejection fraction ( HFrEF ) in PARADIGM-HF.

The association between uric acid concentration and the primary composite outcome of cardiovascular death or heart failure hospitalization, its components, and all-cause mortality was examined using Cox regression analyses among 8213 patients using quintiles ( Q1-Q5 ) of uric acid concentration adjusted for baseline prognostic variables including estimated glomerular filtration rate ( eGFR ), diuretic dose, and log N-terminal pro-brain natriuretic peptide.

Change in uric acid concentration from baseline over 12 months was also evaluated in each treatment group.

Patients in Q5 ( SUA greater than or equal to 8.6 mg/dL ) compared with Q1 ( less than 5.4 mg/dL ) were younger ( 62.8 vs. 64.2 years ), more often male ( 88.7% vs. 63.1% ), had lower systolic blood pressure ( 119 vs. 123 mmHg ), lower eGFR ( 57.4 vs. 76.6 mL/min/1.73 m2 ), and greater diuretic use.

Higher uric acid concentration 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 ], hospitalization for heart failure [ 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 and Valsartan combination has reduced uric acid concentration by 0.24 ( 0.17-0.32 ) mg/dL over 12 months ( P less than 0.0001 ).

Sacubitril and Valsartan improved outcomes, irrespective of uric acid concentration.

In conclusion, serum uric acid concentration was an independent predictor of worse outcomes after multivariable adjustment in patients with HFrEF.
Compared with Enalapril, Sacubitril and Valsartan combination has reduced uric acid concentration and improved outcomes irrespective of uric acid concentration. ( Xagena )

Mogensen UM et al, Eur J Heart Fail 2017; Epub ahead of print

XagenaMedicine_2017



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