Clinical practice frequently falls short of sacubitril/valsartan (Sac/Val) doses that were successful in clinical studies for heart failure with reduced ejection fraction (HFrEF). For a study, researchers sought to determine the relationships between Sac/Val dosages and alterations in prognostic biomarkers, health status, and cardiac remodeling in people with HFrEF during the course of a year of therapy with Sac/Val administered/usual care.

A total of 794 individuals with HFrEF (ejection fraction [EF] ≤40%) were grouped into tertiles based on their average daily dosages of Sac/Val. The Kansas City Cardiomyopathy Questionnaire-23 scores, biomarker changes (N-terminal pro-B-type natriuretic peptide, high-sensitivity cardiac troponin T, soluble ST2, atrial natriuretic peptide, urinary cyclic guanosine monophosphate), and cardiac reverse remodeling parameters (left ventricular EF, indexed left atrial & ventricular volumes, & E/e’) were evaluated from baseline to 12 months.

Tertile 1 received a low dosage of 112 mg, Tertile 2 a moderate dose of 342 mg, and Tertile 3 a high dose of 379 mg daily (high dose). Prognostic biomarker alterations were similar across all dosage tertiles. Regardless of the dosing group, improvements in Kansas City Cardiomyopathy Questionnaire-23 scores were comparable. In all dose categories, there was consistent reverse cardiac remodeling; the median absolute left ventricular EF improvement across HF dose groups was 9.3%, 8.7%, and 10.2% for low, moderate, and high doses, respectively. Across dose categories, there were also comparable improvements in left atrial and ventricular volumes and E/e’.

Similar improvements in prognostic biomarkers, health status, and cardiac remodeling were seen across HFrEF patients across different Sac/Val dosages.

Reference: jacc.org/doi/10.1016/j.jacc.2022.08.737