Entresto is Indicated for CHF with Reduced Ejection Fraction and CKD Stage IV
Entresto (sacubitril/valsartan) is indicated for this patient with heart failure with reduced ejection fraction (HFrEF) and CKD stage IV, and should replace the current lisinopril therapy. 1
Indication and Benefits
- Entresto is indicated for patients with HFrEF (EF ≤40%) with NYHA class II-IV symptoms, making it appropriate for this patient with an EF of 20-25% 1
- Recent evidence shows that sacubitril/valsartan improves left ventricular systolic and diastolic function in patients with HFrEF and end-stage kidney disease 2
- Long-term sacubitril/valsartan therapy is associated with improved outcomes and renal protection in patients with HFrEF, with effects maintained in both CKD and preserved renal function 3
Implementation Strategy
- The patient is currently on lisinopril (ACE inhibitor), which should be discontinued with a mandatory 36-hour washout period before initiating Entresto to avoid angioedema 1
- For patients with severe renal impairment (CKD stage IV), start with the lowest dose of Entresto (24/26 mg twice daily) 1
- Titrate the dose slowly, doubling every 2-4 weeks as tolerated, aiming for the target dose of 97/103 mg twice daily if possible 1
Medication Adjustments
- Continue metoprolol succinate as beta-blockers are a cornerstone of HFrEF therapy 4, 1
- Consider monitoring and potentially adjusting the torsemide dose, as diuretic requirements may decrease due to enhanced natriuresis with Entresto 1
- Monitor renal function and electrolytes closely, particularly potassium levels, as hyperkalemia rates are higher in patients with renal dysfunction (16.3% vs 6.5% in those without renal dysfunction) 5
Monitoring Recommendations
- Check renal function and electrolytes within 1-2 weeks after initiation and with each dose increase 1
- Monitor blood pressure closely, especially during initiation and dose titration, as hypotension is a common side effect 1
- If hypotension occurs, consider temporary dose reduction rather than discontinuation, as 40% of patients who required temporary dose reduction were subsequently restored to target doses 1
Special Considerations for CKD Stage IV
- Despite CKD stage IV, Entresto has shown benefits in patients with advanced kidney disease, with studies demonstrating improvements in estimated GFR in patients with renal dysfunction 5
- The TRANSITION study showed that most patients with HFrEF and concomitant renal dysfunction tolerated early initiation of sacubitril/valsartan and showed significant improvements in estimated GFR and cardiac biomarkers 5
- Be vigilant for potential adverse effects that occur more frequently in CKD patients, including hyperkalemia (16.3%), worsening heart failure (9.7%), and renal impairment (6.4%) 5
Potential Pitfalls to Avoid
- Do not co-administer Entresto with ACE inhibitors (lisinopril) - ensure the 36-hour washout period is strictly observed 1
- Do not underdose due to concerns about renal function - while starting at a lower dose is appropriate, attempt to titrate to the maximum tolerated dose as benefits are dose-dependent 1
- Do not discontinue therapy prematurely due to mild laboratory changes or asymptomatic hypotension 1
- Do not neglect to monitor for drug interactions, particularly with statins that are substrates of OATP1B1, OATP1B3, OAT1, and OAT3 transporters 1