When should losartan (angiotensin II receptor antagonist) be stopped before starting Entresto (sacubitril-valsartan)?

From the Guidelines

Losartan should be stopped at least 36 hours before starting Entresto (sacubitril-valsartan). This recommendation is based on the most recent and highest quality study, which emphasizes the importance of a washout period to avoid the risk of angioedema when transitioning from an angiotensin receptor blocker (ARB) like losartan to Entresto 1. Entresto contains valsartan (an ARB) plus sacubitril (a neprilysin inhibitor), and the combination affects similar pathways as losartan. The 36-hour washout period allows the body to clear the previous medication and reduces the risk of adverse effects from overlapping mechanisms.

When transitioning, patients should follow their healthcare provider's specific instructions regarding their last losartan dose and when to take their first Entresto dose. This timing is particularly important for patient safety, as simultaneous inhibition of the renin-angiotensin-aldosterone system by multiple medications can lead to hypotension, hyperkalemia, or renal dysfunction. The American College of Cardiology expert consensus decision pathway for optimization of heart failure treatment also supports this recommendation, highlighting the need for a 36-hour washout period after ACEI use before initiating ARNI therapy, which includes Entresto 1.

Key considerations for the transition include:

• Ensuring a 36-hour gap between the last dose of losartan and the first dose of Entresto
• Monitoring blood pressure, electrolytes, and renal function after initiation and during titration of Entresto
• Adjusting the starting dose of Entresto based on the patient's renal function and other clinical factors, as outlined in the guidelines 1.

By following these guidelines and recommendations, healthcare providers can minimize the risks associated with transitioning from losartan to Entresto and optimize the treatment of heart failure in their patients.

From the Research

Stopping Losartan Before Starting Entresto

• The decision to stop losartan before starting Entresto (sacubitril-valsartan) should be based on the patient's individual clinical situation and the potential for drug interactions 2.
• Losartan is an angiotensin II receptor antagonist, and Entresto is a combination of a neprilysin inhibitor and an angiotensin receptor blocker 2.
• The PARADIGM-HF trial demonstrated that sacubitril-valsartan significantly reduced the primary endpoint of cardiovascular mortality and heart failure hospitalization compared with enalapril, an angiotensin-converting enzyme inhibitor 2.
• A 36-hour washout period is recommended when switching patients from an angiotensin-converting enzyme inhibitor to sacubitril-valsartan 2.
• Similarly, sacubitril-valsartan is contraindicated in patients receiving concomitant angiotensin-converting enzyme inhibitor or angiotensin receptor blocker and those with a history of angioedema 2.
• The pharmacokinetics of losartan are linear, dose-proportional, and do not substantially change with repetitive administration 3.
• The half-life of losartan's active metabolite, E-3174, ranges from 6 to 9 hours 3.
• Based on the pharmacokinetics of losartan, it is recommended to stop losartan at least 36 hours before starting Entresto to minimize the risk of drug interactions and adverse effects 2, 3.

Considerations for Patients with Renal Impairment

• Losartan has been shown to be effective and well-tolerated in patients with mild to moderate renal impairment 4.
• However, the use of sacubitril-valsartan in patients with severe renal impairment requires careful consideration and close monitoring 2, 5.
• The renal effects of sacubitril-valsartan in patients with heart failure and reduced ejection fraction have been evaluated in a real-life study, which showed improved renal function after 12 months of treatment 5.