Acute Diuretic-Sparing Effects of Sacubitril-Valsartan: Staying in the Loop

Abstract

Background: Previous literature has suggested a potential diuretic sparing effect as early as 6 months following sacubitril-valsartan initiation in patients with heart failure with reduced ejection fraction (HFrEF); however, whether this effect manifests earlier after initiation is unclear. Objective: To evaluate the acute diuretic-sparing effects of sacubitril-valsartan. Methods: This was a single-center, retrospective analysis of outpatients with HFrEF initiated on sacubitril-valsartan with follow up within 90 ± 30 days and a concomitant loop diuretic prescription. The primary outcome was the percent of patients with an increase, decrease or no change in loop diuretic total daily dose (TDD). Key secondary outcomes included change in loop diuretic TDD (mg furosemide equivalents) and hospital admissions or emergency department (ED) visits. Results: A total of 145 patients were included (overall cohort) with 120 continuing sacubitril-valsartan at follow up (on-treatment cohort). In the on-treatment cohort, 20% (n = 24) had a reduction in loop diuretic TDD and 10% had an increase (n = 12). Median change in loop diuretic TDD was unchanged from baseline to follow up (p 0.13). In patients on >80 mg TDD of furosemide at baseline (n = 9), mean change was-53 ± 44 mg (p 0.006). Hospitalizations (6.2%) and ED visits (0.7%) for heart failure were infrequent. Conclusion: Patients may require a loop diuretic dose reduction within 2-3 months following sacubitril-valsartan initiation. This diuretic-sparing effect appears larger in those on higher baseline loop diuretic doses, and closer follow up may be warranted for these patients.

Sacubitril/Valsartan Does Not Change the Use and Dose of Loop Diuretics in Patients With Heart Failure With Reduced Ejection Fraction

“…The study was also limited by a small sample size of 120 patients. 6 Our study included more than 400 patients and showed that there were no significant differences in the dose of loop diuretic during 6-month follow-up period following the initiation of sacubitril/valsartan therapy. The diuretic effects of sacubitril/valsartan may not be clinically significant during 6-month follow-up period.…”

“…Sacubitril is a neprilysin inhibitor which allows for increased expression of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP). 6 Wang et al compared the effects of sacubitril/valsartan to the effects of valsartan alone, on natriuresis, diuresis, and serum potassium levels in Asian patients with salt-sensitive hypertension. 7 They found that the first dose of sacubitril/ valsartan significantly increased 6-and 24-hour natriuresis and diuresis compared to the first dose of valsartan only.…”

“…Another retrospective cohort study by Orvin et al investigated the effects of sacubitril/valsartan on the total daily dose of loop diuretics during the 3 ± 1 months following the initiation of sacubitril/valsartan. 6 They found that only 20% of adults experiencing HF with reduced ejection fraction (n = 24) required a reduction in their total daily dose (TDD) of loop diuretics, 70% (n = 84) had no changes in their TDD, and 10% required an increased TDD of loop diuretics (n = 12). 6 The median TDD of loop diuretics at baseline and follow-up was not statistically different (40 mg [interquartile range (IQR) 20-80] vs 40 mg [IQR 20-80]; P = .13).…”

“…6 They found that only 20% of adults experiencing HF with reduced ejection fraction (n = 24) required a reduction in their total daily dose (TDD) of loop diuretics, 70% (n = 84) had no changes in their TDD, and 10% required an increased TDD of loop diuretics (n = 12). 6 The median TDD of loop diuretics at baseline and follow-up was not statistically different (40 mg [interquartile range (IQR) 20-80] vs 40 mg [IQR 20-80]; P = .13). However, Orvin et al 6 did not evaluate longitudinal changes in loop diuretic use and dose and instead collected diuretic use and dose information at only 2 time points, before and after sacubitril/valsartan initiation.…”

“…4,5 One single-center, small-scale study has investigated the effect of sacubitril/valsartan on the required dose of loop diuretic over the short term (i.e., during the 3 months after the initiation of sacubitril/ valsartan) but it only had 2 time points, before and after sacubitril/valsartan initiation and did not evaluate longitudinal changes in loop diuretic use and dose. 6 The objective of this study was to investigate longitudinal trends in loop diuretic use and doses during the 6 months following the initiation of sacubitril/valsartan in academic tertiary center-affiliated cardiology clinics.…”