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

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.

journal_name

Eur J Heart Fail

journal_title

European journal of heart failure

authors

Selvaraj S,Claggett BL,Pfeffer MA,Desai AS,Mc Causland FR,McGrath MM,Anand IS,van Veldhuisen DJ,Kober L,Janssens S,Cleland JGF,Pieske B,Rouleau JL,Zile MR,Shi VC,Lefkowitz MP,McMurray JJV,Solomon SD

doi

10.1002/ejhf.1984

subject

Has Abstract

pub_date

2020-11-01 00:00:00

pages

2093-2101

issue

eissn

1388-9842

issn

1879-0844

journal_volume

pub_type

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