Angiotensin-Neprilysin Inhibition and Renal Outcomes in Heart Failure With Preserved Ejection Fraction.

Abstract

BACKGROUND:

In patients with heart failure, chronic kidney disease is common and associated with a higher risk of renal events than in patients without chronic kidney disease. We assessed the renal effects of angiotensin/neprilysin inhibition in patients who have heart failure with preserved ejection fraction enrolled in the PARAGON-HF trial (Prospective Comparison of ARNI With ARB Global Outcomes in HF With Preserved Ejection Fraction).

METHODS:

In this randomized, double-blind, event-driven trial, we assigned 4822 patients who had heart failure with preserved ejection fraction to receive sacubitril/valsartan (n=2419) or valsartan (n=2403). Herein, we present the results of the prespecified renal composite outcome (time to first occurrence of either: ≥50% reduction in estimated glomerular filtration rate (eGFR), end-stage renal disease, or death from renal causes), the individual components of this composite, and the influence of therapy on eGFR slope.

RESULTS:

At randomization, eGFR was 63±19 mL·min-1·1.73 m-2. At study closure, the composite renal outcome occurred in 33 patients (1.4%) assigned to sacubitril/valsartan and 64 patients (2.7%) assigned to valsartan (hazard ratio, 0.50 [95% CI, 0.33-0.77]; P=0.001). The treatment effect on the composite renal end point did not differ according to the baseline eGFR (<60 versus ≥60 mL·min-1·1.73 m-2 (P-interaction=0.92). The decline in eGFR was less for sacubitril/valsartan than for valsartan (-2.0 [95% CI, -2.2 to -1.9] versus -2.7 [95% CI, -2.8 to -2.5] mL·min-1·1.73 m-2 per year).

CONCLUSIONS:

In patients with heart failure with preserved ejection fraction, sacubitril/valsartan reduced the risk of renal events, and slowed decline in eGFR, in comparison with valsartan. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01920711.

• Authors: Finnian R Mc Causland, Martin P Lefkowitz, Brian Claggett, Nagesh S Anavekar, Michele Senni, Mauro Gori, Pardeep S Jhund, Martina M McGrath, Milton Packer, Victor Shi, Dirk J Van Veldhuisen, Faiez Zannad, Josep Comin-Colet, Marc A Pfeffer, John J V McMurray, Scott D Solomon
• Journal: Circulation (Circulation) Vol. 142 Issue 13 Pg. 1236-1245 (09 29 2020) ISSN: 1524-4539 [Electronic] United States
• PMID: 32845715 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Aminobutyrates
• Angiotensins
• Biphenyl Compounds
• sacubitril
• Valsartan
• Neprilysin

Topics

• Aged
• Aged, 80 and over
• Aminobutyrates (administration & dosage)
• Angiotensins (antagonists & inhibitors)
• Biphenyl Compounds (administration & dosage)
• Double-Blind Method
• Glomerular Filtration Rate (drug effects)
• Heart Failure (drug therapy, physiopathology)
• Humans
• Kidney (physiopathology)
• Middle Aged
• Neprilysin (antagonists & inhibitors)
• Renal Insufficiency, Chronic (physiopathology, prevention & control)
• Stroke Volume
• Valsartan (administration & dosage)