Why Not Use Entresto in Patients with Reduced Ejection Fraction?
Entresto (sacubitril/valsartan) should be used in patients with heart failure with reduced ejection fraction (HFrEF) as it is a recommended therapy that reduces mortality, hospitalization, and improves cardiac remodeling compared to ACE inhibitors alone. 1, 2
Indications for Entresto in HFrEF
- Entresto is indicated for patients with HFrEF (EF ≤40%) with NYHA class II-IV symptoms as a replacement for ACE inhibitors or ARBs 1, 2
- It should be administered in conjunction with other guideline-directed medical therapy (GDMT) for heart failure 1
- The European Society of Cardiology recommends sacubitril/valsartan to further reduce the risk of heart failure hospitalization and death in ambulatory patients with HFrEF who remain symptomatic despite optimal treatment 2
Clinical Benefits of Entresto
- Entresto has demonstrated significant improvements in cardiac remodeling, with studies showing increased left ventricular ejection fraction and decreased left ventricular volumes 1
- Real-world data confirm the favorable effectiveness and tolerability observed in clinical trials, with improvements in NYHA class in 37.5% of patients and LVEF improvement ≥5% in 56.3% of patients at one year 3
- Entresto reduces the risk of total worsening heart failure events and cardiovascular death compared to valsartan alone 4
Practical Implementation
- When transitioning from an ACE inhibitor to Entresto, a 36-hour washout period must be strictly observed to avoid angioedema 1
- No washout period is required when switching from an ARB to Entresto 1
- Initial dosing depends on prior therapy:
Considerations for Special Populations
- For patients with severe renal impairment (eGFR <30 mL/min/1.73 m²), moderate hepatic impairment, or elderly patients (≥75 years), start with the lowest dose (24/26 mg twice daily) 1
- In patients with low blood pressure, consider starting with the lowest dose and up-titrating slowly with small increments 1
Managing Common Concerns
Low Blood Pressure
- Symptomatic hypotension in chronic HFrEF can usually be managed through patient education and counseling without reducing HF pharmacotherapy 1
- For patients with low BP who are clinically stable on optimal medical therapy, the low BP is unlikely to be directly caused by GDMT and other causes should be evaluated 1
- Consider starting with the lowest dose of Entresto (24/26 mg twice daily) and up-titrating slowly 1
Renal Function
- Entresto has been associated with lower rates of renal composite endpoints compared to valsartan alone 4
- Monitor renal function and electrolytes, particularly when used with aldosterone antagonists 1
Potential Contraindications or Cautions
- History of angioedema related to previous ACE inhibitor or ARB therapy 1
- Severe renal impairment requires dose adjustment, not avoidance 1
- Concomitant use with ACE inhibitors is contraindicated (must observe 36-hour washout period) 1
In conclusion, there are few reasons not to use Entresto in eligible HFrEF patients, as it has demonstrated superior outcomes compared to ACE inhibitors alone. The main considerations are proper patient selection, appropriate dosing based on individual characteristics, and careful monitoring during initiation and titration.