Novel doses of sacubitril/valsartan in patients unable to tolerate traditional therapy: Effects on N‐terminal pro B‐type natriuretic peptide levels

Abstract

BackgroundWidespread use of angiotensin receptor blocker and neprilysin inhibitor (ARNI) remains low, and many patients are unable to tolerate the medication due to hypotension at the currently recommended starting dose.HypothesisThe aim of this study is to assess if lower than standard doses of ARNI, sacubitril/valsartan (S/V), significantly reduces NT‐proBNP and leads to any change in diuretic dose, serum potassium, or creatinine.MethodsIn a retrospective study of 278 patients who were started on a low dose S/V at a single medical center, 45 patients were selected for the study cohort. Patients were subcategorized to Group 1 (n = 10): very low dose S/V (half a tab of 24/26 mg BID), Group 2 (n = 10): very low dose titrated to low dose S/V, and Group 3 (n = 25): low dose S/V (24/26 mg BID). NT‐proBNP, diuretic dose, serum potassium, and creatinine were compared before and after initiation of S/V.ResultsAmong all groups, there was a significant reduction in NT‐proBNP level (Group 1: p < .01, Group 2: p < .01, and Group 3: p < .001). In addition, there was a significant reduction in diuretic dose across all groups combined (furosemide 53 mg/day vs. 73 mg/day; p = .03), with 17.8% (8/45) patients being able to discontinue their diuretic completely. There was no significant change in potassium or creatinine.ConclusionsLower than standard dose of S/V significantly reduces NT‐proBNP and diuretic requirement without change in potassium or creatinine, which provides hope that patients who cannot tolerate standard doses of S/V due to hypotension may be able to receive the benefits of S/V therapy.

Low- vs high-dose ARNI effects on clinical status, exercise performance and cardiac function in real-life HFrEF patients

“…The interplay between clinical and functional achievements and NT-proBNP levels in this study confirmed previously published data by Pandey et al who found that even lower than standard doses of ARNI were able to reduce the circulating NT-proBNP and loop diuretic requirement, without any relevant change in potassium or serum creatinine [ 22 ]. Though the dose of 50 mg BID has been considered the lowest ARNI dose to be given to HFrEF patients, clinical advantages have also been shown with very low-doses (12/13 mg BID) [ 23 ].…”

Successful treatment of doxorubicin-induced cardiomyopathy with low-dose sacubitril/valsartan: a case report

“…Thus, the application of sacubitril/valsartan resulted in an improvement of the New York Heart Association functional class, myocardial function, and serum N -terminal prohormone of BNP levels. 6–8 These improvements were also observed at lower doses of sacubitril/valsartan, 6 , 13 , 14 consistent with the findings of our case study. Remarkably, in the case presented here, sacubitril/valsartan was initiated at a point at which LVEF recovery has been shown to be highly unlikely in patients with CTRCD.…”

Implication of low dose sacubitril/valsartan

“…Pandey et al demonstrated that even the lower than the standard dose of sacubitril/valsartan reduced NT-proBNP maintaining serum potassium and creatinine levels. 2 Several concerns should improve their findings.…”

“…Although statistically not significant, there are numerically several differences in baseline characteristics, including systolic blood pressure, diuretic dose, and beta-blocker dose, among the three groups stratified by the dose of sacubitril/valsartan. 2 It would be required to adjust for these differences to investigate the independent impact of very low dose sacubitril/valsartan, although a small sample size would not permit such an adjustment.…”

“…The doses of diuretics could not be reduced and the dose of mineralocorticoid was rather reduced in the patients with very low dose sacubitril/valsartan. 2 Email: teimamu@med.u-toyama.ac.jp ORCID Teruhiko Imamura https://orcid.org/0000-0002-7294-7637…”