Effects of sacubitril/valsartan versus valsartan on renal function in patients with and without diabetes and heart failure with preserved ejection fraction: insights from PARAGON-HF.

Abstract

AIMS:

Diabetes is associated with a faster rate of renal function decline in patients with heart failure (HF). Sacubitril/valsartan attenuates the deterioration of renal function to a greater extent in patients with diabetes and HF with reduced ejection fraction compared with renin-angiotensin system inhibitors alone. We assessed whether the same may be true in HF with preserved ejection fraction (HFpEF).

METHODS AND RESULTS:

In the PARAGON-HF trial in patients with HF and left ventricular ejection fraction of ≥45% (n = 4796), we characterized the effects of sacubitril/valsartan on changes in estimated glomerular filtration rate (eGFR) over a period of 192 weeks, and on the pre-specified renal composite outcome (eGFR reduction of ≥50%, end-stage renal disease, or death attributable to renal causes) in patients with (n = 2388) and without diabetes (n = 2408). The decline in eGFR was greater in patients with diabetes than in those without (-2.6 vs. -1.7 ml/min/1.73 m2 per year, p < 0.001), regardless of treatment assignment. Sacubitril/valsartan attenuated decline in eGFR similarly in patients with (-2.2 vs. -2.9 ml/min/1.73 m2 per year, p = 0.001) and without diabetes (-1.5 vs. -2.0 ml/min/1.73 m2 per year, p = 0.006) (pinteraction for difference in eGFR slopes = 0.40). Compared with valsartan, sacubitril/valsartan reduced the renal composite outcome similarly in patients without diabetes (hazard ratio [HR] 0.42, 95% confidence interval [CI] 0.19-0.91) and those with diabetes (HR 0.54, 95% CI 0.33-0.89; pinteraction  = 0.59), as well as across a range of baseline glycated haemoglobin (pinteraction  = 0.71).

CONCLUSION:

Sacubitril/valsartan, compared with valsartan, attenuates the decline of eGFR and reduces clinically relevant kidney events similarly among patients with HFpEF with and without diabetes.

• Authors: Alexander Peikert, Muthiah Vaduganathan, Finnian Mc Causland, Brian L Claggett, Safia Chatur, Milton Packer, Marc A Pfeffer, Faiez Zannad, Martin P Lefkowitz, Burkert Pieske, Hans-Dirk Düngen, John J V McMurray, Scott D Solomon
• Journal: European journal of heart failure (Eur J Heart Fail) Vol. 24 Issue 5 Pg. 794-803 (05 2022) ISSN: 1879-0844 [Electronic] England
• PMID: 35119183 (Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2022 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.

Chemical References

• Aminobutyrates
• Angiotensin Receptor Antagonists
• Biphenyl Compounds
• Drug Combinations
• Tetrazoles
• sacubitril
• Valsartan

Topics

• Aminobutyrates (pharmacology, therapeutic use)
• Angiotensin Receptor Antagonists
• Biphenyl Compounds (pharmacology, therapeutic use)
• Diabetes Mellitus (drug therapy, epidemiology)
• Drug Combinations
• Heart Failure (drug therapy)
• Humans
• Kidney (drug effects, physiology)
• Stroke Volume
• Tetrazoles (pharmacology, therapeutic use)
• Valsartan (pharmacology, therapeutic use)
• Ventricular Function, Left