From the Guidelines
Entresto (sacubitril/valsartan) should be used with caution in patients with End-Stage Renal Disease (ESRD), with careful consideration of the potential risks and benefits. When considering the use of Entresto in ESRD patients, several key factors must be taken into account, including the patient's overall clinical status, comorbidities, and risk factors 1. The medication's unique mechanism of action, combining neprilysin inhibition with angiotensin receptor blockade, can provide cardiovascular benefits for patients with heart failure with reduced ejection fraction, but its use in ESRD patients requires careful monitoring due to the potential for increased exposure to the active components, particularly sacubitril's active metabolite 1.
Some key considerations for using Entresto in ESRD patients include:
- Starting with a reduced dose and cautious uptitration based on tolerability
- Close monitoring of kidney function, blood pressure, potassium levels, and volume status
- Being aware of the potential risks, including hypotension, hyperkalemia, and worsening renal function, which may be more pronounced in ESRD patients
- Individualizing treatment decisions based on the patient's specific clinical status and risk factors
It's also important to note that patients with ESRD were underrepresented in major clinical trials, so evidence for efficacy in this population is limited 1. However, guidelines suggest that RAAS inhibitors, such as Entresto, can be used in patients with moderate CKD, but with careful monitoring of renal function and serum potassium levels 1.
In patients with severely reduced renal function, such as those with ESRD, the use of Entresto requires careful consideration and monitoring, and alternative treatments may need to be considered 1. Ultimately, the decision to use Entresto in an ESRD patient should be made on a case-by-case basis, taking into account the individual patient's needs and risk factors.
From the FDA Drug Label
In adults and pediatric patients with severe renal impairment estimated glomerular filtration rate (eGFR less than 30 mL/min/1. 73 m2), start sacubitril and valsartan tablets at half the usually recommended starting dose.
As a consequence of inhibiting the renin-angiotensin-aldosterone system (RAAS), decreases in renal function may be anticipated in susceptible individuals treated with sacubitril and valsartan.
Entresto (sacubitril/valsartan) in ESRD patients:
- The FDA drug label recommends dose adjustment for patients with severe renal impairment (eGFR < 30 mL/min/1.73 m2) by starting at half the recommended dose.
- Patients with ESRD may be at increased risk of decreased renal function, hyperkalemia, and hypotension when taking sacubitril and valsartan.
- Dose adjustment and close monitoring are necessary when using Entresto in patients with ESRD, as the drug may worsen renal function or cause other adverse effects.
- Consider the potential risks and benefits of using Entresto in ESRD patients and closely monitor serum creatinine, potassium levels, and blood pressure. 2 2
From the Research
Considerations for Using Entresto in ESRD Patients
- The use of Entresto (sacubitril/valsartan) in patients with End-Stage Renal Disease (ESRD) requires careful consideration of the potential benefits and risks 3, 4, 5, 6.
- Studies have shown that sacubitril/valsartan can improve treatment outcomes in patients with ESRD accompanied by heart failure, including reducing blood pressure, improving left ventricular ejection fraction (LVEF), and reducing the risk of cardiovascular hospitalization 4, 5, 6.
- However, some patients with ESRD may not respond well to sacubitril/valsartan treatment, and may experience adverse effects such as symptomatic hypotension and dizziness 6.
- Metabolomics analysis has identified potential biomarkers for predicting the clinical efficacy of sacubitril/valsartan in patients with ESRD, including lysophosphatidylcholine (LysoPC) metabolites and the enzyme phospholipase A2 group IVA (PLA2G4A) 3.
- The long-term outcomes of sacubitril/valsartan treatment in patients with HFrEF and coexisting ESRD have been shown to be beneficial, with significantly lower 5-year all-cause mortality rates and greater LVEF improvement compared to candesartan or valsartan 5.
- It is essential to monitor patients with ESRD closely while on sacubitril/valsartan treatment, including regular assessment of blood pressure, kidney function, and cardiovascular biomarkers 4, 6.
Key Findings
- Sacubitril/valsartan can be effective in reducing blood pressure and improving LVEF in patients with ESRD and heart failure 4, 5, 6.
- The treatment should be individualized, and patients should be monitored closely for potential adverse effects 6.
- Further studies are needed to fully understand the benefits and risks of sacubitril/valsartan treatment in patients with ESRD 3, 4, 5, 6.