From the Guidelines
Entresto (sacubitril/valsartan) should be used with extreme caution in patients with end-stage renal disease (ESRD) due to limited clinical data and concerns about drug accumulation, and a reduced starting dose of 24/26 mg twice daily is recommended with careful monitoring for hypotension, hyperkalemia, and worsening renal function. When considering the use of Entresto in ESRD patients, it is crucial to weigh the potential benefits against the risks, particularly given the medication's pharmacokinetics and the lack of extensive clinical trial data in this population 1.
Key Considerations
- The medication's components, including sacubitril and valsartan, are affected by renal clearance, with sacubitril's active metabolite accumulating significantly in ESRD patients.
- Patients with severe renal impairment (eGFR <30 mL/min/1.73m²) were largely excluded from major clinical trials, limiting the available data on Entresto's safety and efficacy in this group.
- The use of Entresto in ESRD patients may require careful dose adjustment and monitoring due to the potential for hypotension, hyperkalemia, and worsening renal function, as outlined in the 2021 update to the 2017 ACC expert consensus decision pathway for optimization of heart failure treatment 1.
Clinical Implications
- Alternative heart failure medications with better safety profiles in ESRD, such as certain beta-blockers, might be more appropriate for these patients.
- For ESRD patients on dialysis, the blood pressure-lowering effects of Entresto may pose additional hemodynamic challenges, necessitating close monitoring and potentially adjusting the dialysis regimen.
- The decision to use Entresto in ESRD patients should be made on a case-by-case basis, taking into account the individual patient's clinical status, comorbidities, and potential risks and benefits, as well as the availability of alternative treatment options.
From the FDA Drug Label
8.7 Renal Impairment No dose adjustment is required in patients with mild (eGFR 60 to 90 mL/min/1.73 m2) to moderate (eGFR 30 to 60 mL/min/1. 73 m2) renal impairment. Half of the starting dose is recommended in adult and pediatric patients with heart failure and with severe renal impairment (eGFR less than 30 mL/min/1.73 m2).
10 OVERDOSAGE ... Sacubitril and valsartan is unlikely to be removed by hemodialysis because of high protein binding.
The use of Entresto (sacubitril/valsartan) in patients with End-Stage Renal Disease (ESRD) is not directly addressed in the label. However, it is stated that sacubitril and valsartan is unlikely to be removed by hemodialysis. For patients with severe renal impairment (eGFR less than 30 mL/min/1.73 m2), the recommended dose is half of the starting dose.
- Key points:
- No dose adjustment for mild to moderate renal impairment
- Half of the starting dose for severe renal impairment
- Unlikely to be removed by hemodialysis 2
From the Research
Entresto in ESRD
- Entresto, also known as sacubitril/valsartan, is a medication used to treat heart failure with reduced ejection fraction (HFrEF) 3, 4, 5.
- In patients with end-stage renal disease (ESRD), the use of Entresto has been shown to be effective in reducing heart failure hospitalization and cardiovascular mortality 4.
- A study published in 2020 found that Entresto reduced high-sensitive troponin T (hsTnT) and soluble ST2 (sST2) levels, and improved left ventricular ejection fraction (LVEF) in HFrEF patients with ESRD on dialysis 4.
- Another study published in 2019 reported the case of a patient with heart failure and ESRD who was treated with Entresto and showed symptomatic improvement and a reduction in NT-proBNP levels 5.
- However, it is important to note that the use of Entresto in patients with ESRD requires careful consideration of the patient's individual characteristics and medical history, as well as close monitoring for potential adverse effects such as symptomatic hypotension and dizziness 4.
- Metabolomics analysis has identified potential biomarkers for predicting the clinical efficacy of Entresto in patients with ESRD and heart failure, including lysophosphatidylcholine (LysoPC) metabolites and the enzyme phospholipase A2 group IVA (PLA2G4A) 3.
Management of ESRD
- ESRD is a condition in which the kidneys are no longer able to function adequately to support long-term survival without kidney transplantation or dialysis 6, 7.
- The management of ESRD typically involves renal replacement therapy (RRT) via dialysis or kidney transplantation, as well as the management of complications such as hyperkalemia, hypervolemia, metabolic acidosis, anemia, and protein-calorie malnutrition 6, 7.
- Controlling blood pressure and volume control through adequate dialysis and sodium restriction are important aspects of managing ESRD 6.
- Vaccination against seasonal influenza, tetanus, hepatitis B, human papillomavirus, and Streptococcus pneumoniae is recommended for patients with ESRD 6.