Renal Effects and Associated Outcomes During Angiotensin-Neprilysin Inhibition in Heart Failure.

Abstract

OBJECTIVES:

The purpose of this study was to evaluate the renal effects of sacubitril/valsartan in patients with heart failure and reduced ejection fraction.

BACKGROUND:

Renal function is frequently impaired in patients with heart failure with reduced ejection fraction and may deteriorate further after blockade of the renin-angiotensin system.

METHODS:

In the PARADIGM-HF (Prospective Comparison of ARNI with ACE inhibition to Determine Impact on Global Mortality and Morbidity in Heart Failure) trial, 8,399 patients with heart failure with reduced ejection fraction were randomized to treatment with sacubitril/valsartan or enalapril. The estimated glomerular filtration rate (eGFR) was available for all patients, and the urinary albumin/creatinine ratio (UACR) was available in 1872 patients, at screening, randomization, and at fixed time intervals during follow-up. We evaluated the effect of study treatment on change in eGFR and UACR, and on renal and cardiovascular outcomes, according to eGFR and UACR.

RESULTS:

At screening, the eGFR was 70 ± 20 ml/min/1.73 m2 and 2,745 patients (33%) had chronic kidney disease; the median UACR was 1.0 mg/mmol (interquartile range [IQR]: 0.4 to 3.2 mg/mmol) and 24% had an increased UACR. The decrease in eGFR during follow-up was less with sacubitril/valsartan compared with enalapril (-1.61 ml/min/1.73 m2/year; [95% confidence interval: -1.77 to -1.44 ml/min/1.73 m2/year] vs. -2.04 ml/min/1.73 m2/year [95% CI: -2.21 to -1.88 ml/min/1.73 m2/year ]; p < 0.001) despite a greater increase in UACR with sacubitril/valsartan than with enalapril (1.20 mg/mmol [95% CI: 1.04 to 1.36 mg/mmol] vs. 0.90 mg/mmol [95% CI: 0.77 to 1.03 mg/mmol]; p < 0.001). The effect of sacubitril/valsartan on cardiovascular death or heart failure hospitalization was not modified by eGFR, UACR (p interaction = 0.70 and 0.34, respectively), or by change in UACR (p interaction = 0.38).

CONCLUSIONS:

Compared with enalapril, sacubitril/valsartan led to a slower rate of decrease in the eGFR and improved cardiovascular outcomes, even in patients with chronic kidney disease, despite causing a modest increase in UACR.

• Authors: Kevin Damman, Mauro Gori, Brian Claggett, Pardeep S Jhund, Michele Senni, Martin P Lefkowitz, Margaret F Prescott, Victor C Shi, Jean L Rouleau, Karl Swedberg, Michael R Zile, Milton Packer, Akshay S Desai, Scott D Solomon, John J V McMurray
• Journal: JACC. Heart failure (JACC Heart Fail) Vol. 6 Issue 6 Pg. 489-498 (06 2018) ISSN: 2213-1787 [Electronic] United States
• PMID: 29655829 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• Aminobutyrates
• Angiotensin Receptor Antagonists
• Angiotensins
• Biphenyl Compounds
• Drug Combinations
• Enzyme Inhibitors
• Tetrazoles
• Enalapril
• Valsartan
• Creatinine
• Neprilysin
• sacubitril and valsartan sodium hydrate drug combination

Topics

• Albuminuria (etiology)
• Aminobutyrates (therapeutic use)
• Angiotensin Receptor Antagonists (therapeutic use)
• Angiotensins (antagonists & inhibitors)
• Biphenyl Compounds
• Blood Pressure (drug effects)
• Creatinine (urine)
• Drug Combinations
• Enalapril (therapeutic use)
• Enzyme Inhibitors (therapeutic use)
• Female
• Glomerular Filtration Rate (drug effects)
• Heart Failure (complications, drug therapy, physiopathology)
• Humans
• Male
• Middle Aged
• Neprilysin (antagonists & inhibitors)
• Renal Insufficiency, Chronic (complications, physiopathology)
• Stroke Volume (physiology)
• Tetrazoles (therapeutic use)
• Treatment Outcome
• Valsartan (therapeutic use)