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.

• Authors: Senthil Selvaraj, Brian L Claggett, Marc A Pfeffer, Akshay S Desai, Finnian R Mc Causland, Martina M McGrath, Inder S Anand, Dirk J van Veldhuisen, Lars Kober, Stefan Janssens, John G F Cleland, Burkert Pieske, Jean L Rouleau, Michael R Zile, Victor C Shi, Martin P Lefkowitz, John J V McMurray, Scott D Solomon
• Journal: European journal of heart failure (Eur J Heart Fail) Vol. 22 Issue 11 Pg. 2093-2101 (11 2020) ISSN: 1879-0844 [Electronic] England
• PMID: 32840930 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2020 European Society of Cardiology.

Chemical References

• Aminobutyrates
• Angiotensin Receptor Antagonists
• Angiotensin-Converting Enzyme Inhibitors
• Biphenyl Compounds
• Drug Combinations
• Uric Acid
• Valsartan
• sacubitril and valsartan sodium hydrate drug combination

Topics

• Aged
• Aged, 80 and over
• Aminobutyrates (therapeutic use)
• Angiotensin Receptor Antagonists (therapeutic use)
• Angiotensin-Converting Enzyme Inhibitors (therapeutic use)
• Biphenyl Compounds (therapeutic use)
• Drug Combinations
• Female
• Heart Failure (blood, drug therapy, physiopathology)
• Humans
• Male
• Prospective Studies
• Randomized Controlled Trials as Topic
• Stroke Volume (drug effects)
• Treatment Outcome
• Uric Acid (blood)
• Valsartan (therapeutic use)