They found the gains in the Kansas City Cardiomyopathy Questionnaire-23 scores to be comparable, regardless of dose level. There was no statistical difference at the end of follow-up between overall scores in any of the dose tertiles. The investigators noted a 20-point or higher increase in scores in tertile 1 (32.6%), tertile 2 (34.8%), and tertile 3 (32.8%).

They observed prognostic biomarkers had similar changes at all dose levels. The relative increase of atrial natriuretic peptide and B-type natriuretic peptide were not significantly different across dose levels. The investigators found decreases in high sensitivity cardiac troponin T and soluble suppressor of tumorigenicity-2 to be similar across dose levels. They noted relative N-terminal pro–B-type natriuretic peptide reduction was the same across dose levels.

Limitations of this study include the majority of patients being White and there being fewer women participants. There is also lack of randomization or use of placebo and the impact of various dose levels on survival is not investigated.

“Among patients with HFrEF, similar improvement in prognostic biomarkers, health status, and cardiac remodeling were observed across various Sac/Val [sacubitril/valsartan] doses,” the study authors wrote. “Further data are needed regarding the optimal dose of Sac/Val, including the degree of neprilysin and angiotensin receptor inhibition needed to accrue greatest benefits from the drug.”

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures. Trial or study (PROVE-HF) supported by industry: Novartis Pharmaceuticals.


Mohebi R, Liu Y, Piña IL, et al. Dose-response to sacubitril/valsartan in patients with heart failure and reduced ejection fraction. J Am Coll Cardiol. Published online October 10, 2022. doi:10.1016/j.jacc.2022.08.737