How To Start Entresto If You Already Take An ACE-Inhibitor

In our latest question and answer, the pharmacist discusses why an ACE-Inhibitor needs to be stopped 36 hours before starting Entresto.


My doctor switched me from an ACE inhibitor to Entresto yesterday. The patient literature says I have to wait 36 hours after my last dose of the ACE inhibitor to start Entresto. Is this accurate? 36 hours without a secondary blood pressure medication would be dangerous for me.

Asked by Dave On Nov 18, 2022

Answered by
Medical Content Reviewed By HelloPharmacist Staff

Published Nov 21, 2022
Last updated Nov 21, 2022

Key points

  • You must wait 36 hours after the last dose of your ACE-Inhibitor before taking your first dose of Entresto.
  • This 36-hour window is a washout period that is necessary to reduce the risk of a serious medical condition, angioedema.


You are correct that if you are currently taking an ACE-Inhibitor, you must wait 36 hours after your last dose to start taking Entresto (Sacubitril; Valsartan)

This is explicitly stated in the prescribing information for the drug:

ENTRESTO is contraindicated with concomitant use of an angiotensin-converting enzyme (ACE) inhibitor. If switching from an ACE inhibitor to ENTRESTO allow a washout period of 36 hours between administration of the two drugs.
Entresto Prescribing Information

ACE-Inhibitors include:

  • Lisinopril
  • Enalapril
  • Captopril
  • Fosinopril
  • Moexipril
  • Benazepril
  • Perindopril
  • Quinapril
  • Ramipril
  • Trandolapril

If you are taking any of the above drugs, be sure to only start taking Entresto after it has been 36 hours since your last dose.

Why Is There A Waiting Period?

Entresto is used to treat heart failure with reduced ejection fraction.

In many cases, an individual will already be taking an ACE-Inhibitor before Entresto is prescribed. This seems to be your situation, and there are a few things that a prescriber will look for before prescribing Entresto:

  • You should be tolerating at least a moderate dose of an ACE inhibitor (e.g., lisinopril 7.5 or 10 mg daily) well.
  • Your systolic blood pressure (the top number) should be at least 100 mmHg.
  • You should have no symptoms of low blood pressure (i.e., hypotension).

If you meet the above criteria, Entresto often represents a good medication option to help reduce your risk of complications due to heart failure. 

In terms of starting Entresto, you need to wait 36 hours after the last dose of your ACE-Inhibitor before taking your first dose of Entresto.

This 36-hour window between the last dose of your ACE-Inhibitor and Entresto is known as a 'washout period'. It allows time for your system to metabolize and eliminate the ACE-Inhibitor you have been taking. It must be strictly observed before Entresto is started.

The requirement is in place due to the risk of angioedema, an uncommon, but serious condition that can be life-threatening if untreated. Combining an ACE-Inhibitor and Entresto puts at a significantly higher risk of it occurring.

One study evaluating the risks and safety of Entresto concluded the following:

Clinicians should recognize this safety risk when prescribing sacubitril/valsartan [Entresto] and remain vigilant in counseling patients regarding the signs and symptoms of angioedema. As recommended by the guidelines, avoiding sacubitril/valsartan [Entresto] use concurrently or within 36 hours of the last dose of an ACE inhibitor or in patients with a history of angioedema is also crucial to minimize angioedema risk and prevent patient harm.

J Am Board Fam Med . 2017 Jul-Aug;30(4):556-557.

Is There A Concern With Blood Pressure By Waiting 36 Hours?

As long as your blood pressure is well-controlled, waiting 36 hours after the last dose of your ACE-Inhibitor to start Entresto shouldn't put you at any significant risk of problems.

Several studies have shown that stopping an ACE-Inhibitor doesn't lead to significant increases in blood pressure for at least a few days for most individuals. Your blood pressure may rise slowly as the drug is eliminated from your system, but stopping the drug generally doesn't cause a pronounced 'rebound' effect.

If you are concerned about your blood pressure because of the need to stop your ACE-Inhibitor before starting Entresto, talk to your doctor about your options.

In most cases, no additional medication is necessary, but if your blood pressure is uncontrolled, they may recommend a blood pressure medication (that is not an ACE-Inhibitor) for temporary use.

What Is Entresto?

Entresto is a combination of valsartan and sacubitril. It is used to lower the risk of death and hospitalization in those with certain types of heart failure.

Valsartan is in a class of medications called angiotensin II receptor antagonists and works by blocking the action of certain natural substances that tighten the blood vessels, allowing the blood to flow more smoothly and the heart to pump more efficiently. Sacubitril is in a class of medications called neprilysin inhibitors and works to help control blood volume.

Final Words

I hope the information here was helpful! Write back anytime!


  • Entresto Prescribing Information, AccessFDA
  • Angioedema Spotlight: A Closer Examination of Sacubitril/Valsartan Safety Results, PubMed
  • Angioedema in heart failure patients treated with sacubitril/valsartan (LCZ696) or enalapril in the PARADIGM-HF study, PubMed
  • Angioedema with sacubitril/valsartan: Trial-level meta-analysis of over 14,000 patients and real-world evidence to date, PubMed
  • Life Threatening Angioedema Due to Valsartan/Sacubitril With Previously Well-Tolerated ACE Inhibitor, PubMed
  • Short-term effects of withdrawing angiotensin converting enzyme inhibitor therapy on home self-measured blood pressure in hypertensive patients, PubMed
  • The risk of hypertension after preoperative discontinuation of angiotensin-converting enzyme inhibitors or angiotensin receptor antagonists in ambulatory and same-day admission patients, PubMed
  • Interruption of prolonged ramipril treatment in hypertensive patients: effects on the renin-angiotensin system, PubMed

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