From the Guidelines
No, Entresto (sacubitril/valsartan) should not be taken with an Angiotensin-Converting Enzyme (ACE) inhibitor due to the risk of angioedema and other serious side effects. The use of ACE inhibitors and Entresto together is contraindicated because it can lead to excessive blockade of the renin-angiotensin-aldosterone system, resulting in increased risk of severe hypotension, hyperkalemia, kidney problems, and angioedema 1. If a patient is switching from an ACE inhibitor to Entresto, they must wait at least 36 hours after their last ACE inhibitor dose before starting Entresto, as recommended in the 2021 update to the 2017 ACC expert consensus decision pathway for optimization of heart failure treatment 1.
Some key points to consider when prescribing Entresto include:
- Ensuring a 36-hour washout period after the last ACE inhibitor dose before initiating Entresto
- Selecting the appropriate starting dose of Entresto based on the patient's previous ACE inhibitor or ARB dose
- Monitoring blood pressure, electrolytes, and renal function after initiation and during titration of Entresto
- Avoiding the use of Entresto in patients with a history of angioedema, as it may increase the risk of recurrence 1
It is essential to prioritize the patient's safety and follow the recommended guidelines when prescribing Entresto, considering the potential risks and benefits of this medication. The benefits of Entresto in reducing morbidity and mortality in patients with heart failure with reduced ejection fraction (HFrEF) should be weighed against the potential risks of angioedema and other side effects when deciding whether to prescribe this medication 1.
From the FDA Drug Label
• with concomitant use of ACE inhibitors. Do not administer within 36 hours of switching from or to an ACE inhibitor [see Drug Interactions (7. 1)]
- Entresto (sacubitril/valsartan) is contraindicated with concomitant use of ACE inhibitors.
- It is recommended not to administer Entresto within 36 hours of switching from or to an ACE inhibitor. 2
From the Research
Entresto and ACE Inhibitors
- Entresto (sacubitril/valsartan) is not recommended to be taken with an Angiotensin-Converting Enzyme (ACE) inhibitor 3, 4, 5, 6, 7
- The drug is usually administered in conjunction with other heart failure therapies, instead of an ACE inhibitor or an angiotensin-receptor blocker (ARB) 3
- Studies have shown that sacubitril/valsartan is superior to enalapril, an ACE inhibitor, in reducing the risks of death and hospitalization for heart failure 4, 6, 7
Rationale for Not Combining Entresto with ACE Inhibitors
- The combination of sacubitril with valsartan in a single formulation offers the benefit of concurrent blockade of the renin angiotensin aldosterone system and the inhibition of neprilysin while minimizing angioedema risk 6
- Sacubitril/valsartan has been shown to be a more effective replacement for an ACE inhibitor or an ARB in the treatment of heart failure with reduced ejection fraction (HFrEF) 4, 5
- The use of Entresto in combination with an ACE inhibitor is not recommended due to the increased risk of adverse events such as hypotension and angioedema 3, 7