Should I discontinue losartan (Angiotensin II Receptor Blocker) when initiating Entresto (sacubitril/valsartan)?

Discontinuing Losartan When Starting Entresto (Sacubitril/Valsartan)

Yes, you must discontinue losartan when initiating Entresto (sacubitril/valsartan) therapy as concomitant use of an ARB with Entresto is contraindicated and potentially harmful.

Rationale for Discontinuation

• Entresto is a combination drug containing valsartan (an ARB) and sacubitril (a neprilysin inhibitor), making additional ARB therapy with losartan redundant and potentially dangerous 1

• Concomitant use of Entresto with another ARB like losartan can lead to:

  • Excessive blockade of the renin-angiotensin system 1
  • Increased risk of hypotension 1
  • Potential renal dysfunction 1
  • Hyperkalemia 1

Proper Transition Protocol

• When switching from losartan to Entresto:

  • Discontinue losartan completely 1
  • Wait 24 hours after the last dose of losartan before initiating Entresto 1
  • Start with the appropriate initial dose of Entresto based on the patient's clinical status 1

• If the patient was previously on an ACE inhibitor rather than an ARB, a 36-hour washout period would be required before starting Entresto to reduce the risk of angioedema 1

Clinical Considerations

• Entresto has demonstrated superior outcomes compared to ACE inhibitors in heart failure with reduced ejection fraction (HFrEF):

  • Reduced cardiovascular mortality 2
  • Decreased heart failure hospitalizations 1
  • Improved quality of life 2

• Discontinuing sacubitril/valsartan and returning to an ARB like losartan has been associated with:

  • Worsening of NYHA functional class 3
  • Deterioration of left ventricular ejection fraction 3
  • Increased end-diastolic volume 3

Monitoring After Transition

• After switching from losartan to Entresto, monitor:

  • Blood pressure (risk of hypotension is higher with Entresto than with ARBs alone) 1
  • Renal function and electrolytes within 1-2 weeks 1
  • Signs of angioedema (rare but serious side effect) 1

• If the patient has borderline blood pressure (systolic BP ≤100 mmHg), consider:

  • Careful administration and close follow-up 1
  • Possible reduction in diuretic dose in non-congested patients to mitigate hypotensive effects 1

Special Considerations

• In patients with severe renal impairment (eGFR <30 mL/min/1.73 m²), start with a reduced dose of Entresto (24/26 mg twice daily) 1

• Entresto is contraindicated in:

  • Pregnancy 1
  • Severe hepatic impairment (Child-Pugh C) 1
  • History of angioedema with ACE inhibitors or ARBs 1

Remember that Entresto already contains an ARB component (valsartan), making additional ARB therapy with losartan unnecessary and potentially harmful to the patient's morbidity and mortality outcomes.