From the Guidelines
Entresto (sacubitril/valsartan) requires a 36-hour washout period after stopping lisinopril to prevent the risk of angioedema, as recommended by the 2017 ACC/AHA/HFSA guideline update 1 and further supported by the 2021 ACC expert consensus decision pathway update 1. This washout period is necessary because Entresto contains sacubitril, which inhibits neprilysin, an enzyme that breaks down bradykinin. When combined with the ACE inhibitor effects of lisinopril, which also increases bradykinin levels, there is a significantly elevated risk of angioedema, a potentially life-threatening swelling that can affect the face, lips, tongue, and airway. The 36-hour washout allows lisinopril to be cleared from the body before starting Entresto, as stated in the guidelines 1. Key points to consider during this transition include:
- Patients should stop taking lisinopril and wait 36 hours before beginning Entresto at the prescribed dose.
- During this transition period, patients should monitor for any signs of facial or throat swelling, difficulty breathing, or other unusual symptoms and seek immediate medical attention if these occur.
- The risk of angioedema is a critical consideration, and the guidelines explicitly state that ARNI should not be administered concomitantly with ACE inhibitors or within 36 hours of the last dose of an ACE inhibitor 1.
- Additionally, ARNI therapy should not be administered in patients with a history of angioedema because of the concern that it will increase the risk of a recurrence of angioedema 1. This precaution is essential for patient safety when switching from an ACE inhibitor like lisinopril to Entresto therapy, and healthcare providers should carefully follow the recommended guidelines to minimize the risk of adverse events.
From the FDA Drug Label
If switching from an ACE inhibitor to sacubitril and valsartan tablet allow a washout period of 36 hours between administration of the two drugs [see Contraindications (4) and Drug Interactions (7.1)].
The reason Entresto (sacubitril/valsartan) requires a washout period after discontinuing Lisinopril (angiotensin-converting enzyme inhibitor) is due to the contraindication of concomitant use of an ACE inhibitor with sacubitril and valsartan tablet. A 36-hour washout period is recommended to avoid potential interactions between the two drugs 2 2.
From the Research
Background on Entresto (sacubitril/valsartan) and Lisinopril
- Entresto (sacubitril/valsartan) is an angiotensin receptor neprilysin inhibitor (ARNI) used in the treatment of heart failure with reduced ejection fraction [(3,4,5,6,7)].
- Lisinopril is an angiotensin-converting enzyme inhibitor (ACEI) also used in the treatment of heart failure and hypertension [(3,4,6,7)].
Rationale for Washout Period
- The washout period is recommended when switching from an ACEI like Lisinopril to an ARNI like Entresto due to the increased risk of angioedema [(3,4,5)].
- Angioedema is a potentially life-threatening side effect that can occur when ACEIs and ARNIs are used together or in close succession [(3,4,5)].
- The recommended washout period is typically 36 hours [(3,4)].
Clinical Evidence
- Studies have shown that the rate of angioedema is low in patients treated with sacubitril/valsartan, but it is still a concern when switching from ACEIs [(3,4,5)].
- The PARADIGM-HF study demonstrated a low rate of confirmed angioedema events in patients treated with sacubitril/valsartan compared to enalapril 3.
- A retrospective cohort study found that 67% of patients received the full 36-hour washout period when transitioning from ACEI to ARNI, with no significant differences in hospital readmissions or adverse effects 4.
Mechanism of Action
- Sacubitril/valsartan works by inhibiting the enzyme neprilysin and blocking angiotensin II receptors, which reduces the degradation of natriuretic peptides and other counterregulatory peptide systems [(6,7)].
- This mechanism of action is different from ACEIs, which only block the conversion of angiotensin I to angiotensin II [(6,7)].