Entresto Therapy for Heart Failure with Reduced Ejection Fraction

Indication and Benefits

Entresto is indicated for patients with heart failure with reduced ejection fraction (HFrEF) with NYHA class II-IV symptoms, making it appropriate for patients with an ejection fraction of 20-25% 1

The American College of Cardiology recommends discontinuing ACE inhibitors, such as lisinopril, with a mandatory 36-hour washout period before initiating Entresto to avoid angioedema 1
For patients with severe renal impairment, 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

The American Heart Association recommends continuing beta-blockers, such as metoprolol succinate, as they are a cornerstone of HFrEF therapy 2, 1
Consider monitoring and potentially adjusting the diuretic dose, as diuretic requirements may decrease due to enhanced natriuresis with Entresto 1

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

Do not co-administer Entresto with ACE inhibitors, such as 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