Study of Effects of Sacubitril/Valsartan vs. Enalapril on Aortic Stiffness in Patients With Mild to Moderate HF With Reduced Ejection Fraction

Summary

To determine whether treatment with sacubitril/valsartan provides a superior effect on aortic characteristic impedance compared to enalapril in patients with heart failure and reduced ejection fraction (left ventricular ejection fraction \[LVEF\] ≤ 40%) after 12 weeks of treatment. The primary endpoint is the change in aortic characteristic impedance (Zc = dP/dQ in early systole) between baseline and Week 12.

Timeline

Start

2016-08-17

Primary completion

2018-12-13

Completion

2019-01-26

Outcome

Missed primary endpoint

paper treatment difference, -2.2 [95% CI, -17.6 to 13.2] dyne × s/cm5; P = .78 PMID 31475296 ↗

paper Treatment of HFrEF with sacubitril-valsartan, compared with enalapril, did not significantly reduce central aortic stiffness. PMID 31475296 ↗

Publications

• Lee S, Claggett BL, Fang JC, Mitchell GF, Ward JH, Solomon SD, Skali H, Desai AS, Hegde SM. Changes in cardiac structure and function are associated with health-related quality of life in heart failure patients with reduced ejection fraction: Results from the EVALUATE-HF trial. Eur J Heart Fail. 2025 Nov;27(11):2582-2593. doi: 10.1002/ejhf.3760. Epub 2025 Jul 18.
• Myhre PL, Claggett BL, Shah AM, Prescott MF, Ward JH, Fang JC, Mitchell GF, Solomon SD, Desai AS. Changes in cardiac biomarkers in association with alterations in cardiac structure and function, and health status in heart failure with reduced ejection fraction: the EVALUATE-HF trial. Eur J Heart Fail. 2022 Jul;24(7):1200-1208. doi: 10.1002/ejhf.2541. Epub 2022 May 30.
• Myhre PL, Prescott MF, Murphy SP, Fang JC, Mitchell GF, Ward JH, Claggett B, Desai AS, Solomon SD, Januzzi JL. Early B-Type Natriuretic Peptide Change in HFrEF Patients Treated With Sacubitril/Valsartan: A Pooled Analysis of EVALUATE-HF and PROVE-HF. JACC Heart Fail. 2022 Feb;10(2):119-128. doi: 10.1016/j.jchf.2021.09.007. Epub 2022 Jan 12.
• Mitchell GF, Solomon SD, Shah AM, Claggett BL, Fang JC, Izzo J, Abbas CA, Desai AS; EVALUATE-HF Investigators*. Hemodynamic Effects of Sacubitril-Valsartan Versus Enalapril in Patients With Heart Failure in the EVALUATE-HF Study: Effect Modification by Left Ventricular Ejection Fraction and Sex. Circ Heart Fail. 2021 Mar;14(3):e007891. doi: 10.1161/CIRCHEARTFAILURE.120.007891. Epub 2021 Mar 5.
• Desai AS, Solomon SD, Shah AM, Claggett BL, Fang JC, Izzo J, McCague K, Abbas CA, Rocha R, Mitchell GF; EVALUATE-HF Investigators. Effect of Sacubitril-Valsartan vs Enalapril on Aortic Stiffness in Patients With Heart Failure and Reduced Ejection Fraction: A Randomized Clinical Trial. JAMA. 2019 Sep 17;322(11):1077-1084. doi: 10.1001/jama.2019.12843.

Drugs

Evaluation	Drug	Modality	Dose	Route
Comparator	Enalapril	Other / unclassified	2.5 mg	Oral
Comparator	Enalapril	Other / unclassified	5 mg	Oral
Comparator	Enalapril	Other / unclassified	10 mg	Oral
Subject	sacubitril/valsartan	Unknown	24 mg	Oral
Subject	sacubitril/valsartan	Unknown	49 mg	Oral
Subject	sacubitril/valsartan	Unknown	97 mg	Oral

Indications