Renal Effects and Associated Outcomes During Angiotensin-Neprilysin Inhibition in Heart Failure

Abstract

Compared with enalapril, sacubitril/valsartan led to a slower rate of decrease in the eGFR and improved cardiovascular outcomes, even in patients with chronic kidney disease, despite causing a modest increase in UACR.

Effect of hyperglycemia and rosiglitazone on renal and urinary neprilysin indb/dbdiabetic mice

“…Furthermore, increased levels of atrial natriuretic peptide (ANP) have been shown to contribute to glomerular hyperfiltration, suggesting potential renal dysfunction in LCZ696‐treated patients (Ortola et al, ). Although detailed and long‐term effects of NEP inhibition need to be studied, the studies above support our conclusion that NEP might have a role in kidney function of diabetic mice (Damman et al, ; Ruggenenti & Remuzzi, ). Thus, new perspective treatment of heart failure with LCZ696 might oppose the protective effect of NEP in other organs such as brain, pancreatic beta islet cells, and kidneys.…”

Clinical practice update on heart failure 2019: pharmacotherapy, procedures, devices and patient management. An expert consensus meeting report of the Heart Failure Association of the European Society of Cardiology

“…[21][22][23] Compared with enalapril, administration of sacubitril/valsartan reduced the incidence of diabetes requiring insulin treatment, 24 and the incidence of hyperkalaemia in those on an MRA. 25 The rate of decline in eGFR was also found lower with sacubitril/valsartan, 26 but this is not yet supported by 'slope of decline' analyses. Hypotension occurs more commonly with sacubitril/valsartan than with enalapril.…”

In‐hospital initiation of sacubitril/valsartan in acute decompensated heart failure: being in the right place at the right time

“…The PARADIGM‐HF investigators found that hypotension was common during the run‐in phase but that hypotensive episodes did not differentially affect permanent study drug discontinuation nor the incremental benefit of sacubitril/valsartan vs. enalapril . Furthermore, they also previously reported that the relative advantage of sacubitril/valsartan, compared to enalapril, in terms of clinical outcomes was maintained independently of whether an increase in urinary albumin/creatinine ratio, a surrogate marker of deteriorating renal function, occurred within the first 30 days of initiating study drug . Therefore, based on the aforementioned evidence, it seems plausible that hypotension, acute kidney injury, and hyperkalaemia are transient episodes that do not portend a differential benefit with treatment in a monitored clinical setting.…”

“…14 Furthermore, they also previously reported that the relative advantage of sacubitril/valsartan, compared to enalapril, in terms of clinical outcomes was maintained independently of whether an increase in urinary albumin/creatinine ratio, a surrogate marker of deteriorating renal function, occurred within the first 30 days of initiating study drug. 15 Therefore, based on the aforementioned evidence, it seems plausible that hypotension, acute kidney injury, and hyperkalaemia are transient episodes that do not portend a differential benefit with treatment in a monitored clinical setting. However, given the relatively high incidence of AEs occurring during the post-discharge period, the TRANSITION study and the PIONEER-HF trial should be leveraged to identify key baseline clinical characteristics associated with short-term safety concerns and/or tolerability issues in order to optimize patient selection for the early implementation of evidence-based neurohormonal antagonists.…”