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. 2020 Nov;22(11):2093-2101.
doi: 10.1002/ejhf.1984. Epub 2020 Sep 30.

Serum uric acid, influence of sacubitril-valsartan, and cardiovascular outcomes in heart failure with preserved ejection fraction: PARAGON-HF

Senthil Selvaraj  1 , Brian L Claggett  2 , Marc A Pfeffer  2 , Akshay S Desai  2 , Finnian R Mc Causland  3 , Martina M McGrath  3 , Inder S Anand  4 , Dirk J van Veldhuisen  5 , Lars Kober  6 , Stefan Janssens  7 , John G F Cleland  8 , Burkert Pieske  9 , Jean L Rouleau  10 , Michael R Zile  11 , Victor C Shi  12 , Martin P Lefkowitz  12 , John J V McMurray  13 , Scott D Solomon  2
Affiliations
Free article

Serum uric acid, influence of sacubitril-valsartan, and cardiovascular outcomes in heart failure with preserved ejection fraction: PARAGON-HF

Senthil Selvaraj et al. Eur J Heart Fail. 2020 Nov.
Free article

Abstract

Aims: This study aimed to determine the prognostic value of serum uric acid (SUA) on outcomes in heart failure (HF) with preserved ejection fraction (HFpEF), and whether sacubitril-valsartan reduces SUA and use of SUA-related therapies.

Methods and results: We analysed 4795 participants from the Prospective Comparison of ARNI [angiotensin receptor-neprilysin inhibitor] with ARB [angiotensin-receptor blockers] Global Outcomes in HF with Preserved Ejection Fraction (PARAGON-HF) trial. We related baseline hyperuricaemia (using age and gender adjusted assay definitions) to the primary outcome [cardiovascular (CV) death and total HF hospitalizations]. We assessed the associations between changes in SUA and Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-OSS) and other cardiac biomarkers from baseline to 4 months. We simultaneously adjusted for baseline and time-updated SUA to determine whether lowering SUA was associated with clinical benefit. The mean (± standard deviation) age of patients was 73 ± 8 years and 52% were women. After multivariable adjustment, hyperuricaemia was associated with increased risk for the primary outcome [rate ratio 1.61, 95% confidence interval (CI) 1.37-1.90]. The treatment effect of sacubitril-valsartan for the primary endpoint was not significantly modified by hyperuricaemia (P-value for interaction = 0.14). Sacubitril-valsartan reduced SUA by 0.38 mg/dL (95% CI 0.31-0.45) compared with valsartan at 4 months, with greater effect in those with elevated SUA vs. normal SUA (-0.51 mg/dL vs. -0.32 mg/dL) (P-value for interaction = 0.031). Sacubitril-valsartan reduced the odds of initiating SUA-related treatments by 32% during follow-up (P < 0.001). After multivariable adjustment, change in SUA was inversely associated with change in KCCQ-OSS and directly associated with high-sensitivity troponin T (P < 0.05). Time-updated SUA was a stronger predictor of adverse outcomes than baseline SUA.

Conclusions: Serum uric acid independently predicted adverse outcomes in HFpEF. Sacubitril-valsartan reduced SUA and the initiation of related therapy compared with valsartan. Reductions in SUA were associated with improved outcomes.

Keywords: Heart failure hospitalization; Heart failure with preserved ejection fraction; Quality of life; Sacubitril-valsartan; Uric acid.

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