Entresto Should Be Held for 36 Hours Before Anesthesia
The FDA label for Entresto (sacubitril/valsartan) explicitly states that patients must be off ACE inhibitor therapy for at least 36 hours before starting Entresto to reduce angioedema risk 1. While this guidance specifically addresses the transition between ACE inhibitors and Entresto, the same 36-hour washout period should be applied when holding Entresto before anesthesia due to the drug's mechanism involving the renin-angiotensin system and its associated perioperative risks.
Rationale for the 36-Hour Hold
The pharmacokinetics of Entresto support this timeframe:
- Sacubitril has an elimination half-life of approximately 1.4 hours
- LBQ657 (active metabolite) has a half-life of 11.5 hours
- Valsartan has a half-life of 9.9 hours 1
Holding the medication for 36 hours allows approximately 3-4 half-lives of the longest-acting component to elapse, substantially reducing drug levels and minimizing the risk of severe intraoperative hypotension.
Why This Matters for Anesthesia
Renin-angiotensin system inhibitors, including ARBs like the valsartan component of Entresto, are associated with severe refractory hypotension during anesthetic induction 2, 3. Research demonstrates that:
- Patients continuing ARBs experience more frequent hypotensive episodes (2±1 vs 1±1 episodes, p<0.01)
- Longer duration of hypotension (8±7 min vs 3±4 min, p<0.01)
- Increased need for vasopressor support 2
- Cases of refractory hypotension have occurred even when ARBs were discontinued 24 hours preoperatively 3
The FDA label confirms hypotension as the most common adverse reaction with Entresto, occurring in 18% of patients 1.
Practical Implementation
For elective surgery:
- Discontinue Entresto 36 hours (approximately 1.5 days) before scheduled anesthesia induction
- Ensure the patient understands to skip at least 2 doses if taking twice daily
- Have vasopressin available intraoperatively, as ARB-induced hypotension may be refractory to standard vasopressors 3
Resumption after surgery:
- Resume Entresto 24-48 hours postoperatively for low bleeding risk procedures
- Resume 48-72 hours postoperatively for high bleeding risk procedures
- Ensure hemodynamic stability and adequate volume status before restarting 1
Important Caveats
Do not abruptly discontinue in unstable heart failure patients. The 2019 ACC Expert Consensus notes that patients recently weaned from intravenous inotropes or extensively diuresed require particular caution when initiating or resuming RAS inhibition 4. For urgent/emergent surgery where the 36-hour hold is not feasible, proceed with heightened vigilance for severe hypotension and have vasopressin immediately available.
Monitor closely for hypotension during induction regardless of the hold period, as individual responses vary and some patients may remain susceptible even after appropriate discontinuation.