Even lower doses of Sacubitril/valsartan suffice for improving outcomes in patients with HFrEF

According to a post hoc analysis of PROVE-HF, patients of heart failure who could not reach target dose of angiotensin receptor/neprilysin inhibitor (ARNI) therapy still benefitted in health status a year later. The study has found that across different sacubitril/valsartan (Sac/Val) dosages, similar improvements in health status, prognostic biomarkers, and cardiac remodeling were seen across heart failure with reduced ejection fraction (HFrEF) patients.

The new study has been published in Journal of the American College of Cardiology.

Clinical practice frequently falls short of sacubitril/valsartan doses that were successful in clinical studies for heart failure with decreased ejection fraction. Reza Mohebi and colleagues undertook this study to examine the relationships between Sac/Val dosages and alterations in prognostic biomarkers, health status, and cardiac remodeling among patients with HFrEF treated for 12 months with Sac/Val given as usual.

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 and ventricular volumes, and E/e') were evaluated from baseline to 12 months.

The key findings of this study were:

1. 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).

2. Prognostic biomarker alterations were similar across all dosage tertiles.

3. Regardless of dosing group, improvements in Kansas City Cardiomyopathy Questionnaire-23 scores were comparable.

4. 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.

5. Across dose categories, there were also comparable improvements in left atrial and ventricular volumes and E/e'.

In conclusion, researchers analyzed distinct Sac/Val dosage trajectories in HFrEF and found that across all 3 dose categories, there was a similar reduction in stress indicators, an increase in health status, and a reversal of the cardiac remodeling process. Additional information is required regarding the ideal dosage of Sac/Val, as well as the level of neprilysin and angiotensin receptor inhibition required to reap the most advantages from the medication.

Reference: 

Mohebi, R., Liu, Y., Piña, I. L., Prescott, M. F., Butler, J., Felker, G. M., Ward, J. H., Solomon, S. D., & Januzzi, J. L., Jr. (2022). Dose-Response to Sacubitril/Valsartan in Patients With Heart Failure and Reduced Ejection Fraction. In Journal of the American College of Cardiology (Vol. 80, Issue 16, pp. 1529–1541). Elsevier BV. https://doi.org/10.1016/j.jacc.2022.08.737