What is the role of Entresto (sacubitril/valsartan) in the management of Non-ST-Elevation Myocardial Infarction (NSTEMI)?

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Last updated: April 17, 2025View editorial policy

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From the Guidelines

Entresto (sacubitril/valsartan) should not be used as a standard treatment for patients immediately following a non-ST-elevation myocardial infarction (NSTEMI), but may be considered in patients who develop heart failure with reduced ejection fraction after an NSTEMI, as it has been shown to reduce HF hospitalization and cardiovascular death compared with ACE-I 1. The primary medications for post-NSTEMI management typically include antiplatelet agents, statins, beta-blockers, and traditional ACE inhibitors or ARBs.

  • Entresto is specifically indicated for patients with chronic heart failure with reduced ejection fraction (HFrEF), not for acute coronary syndromes like NSTEMI.
  • However, a new observational study showed that ACE-I/ARB therapy was associated with significant long-term survival benefit in patients post-PCI for STEMI/non-ST-segment elevation myocardial infarction (NSTEMI) 1.
  • Sacubitril/valsartan may decrease myocardial ischaemia because of its effect in reducing LV wall stress and improving coronary circulation, and the risk of coronary events using sacubitril/valsartan compared with ACE-I was also significantly reduced on post-hoc analyses 1.
  • Before initiating Entresto, patients should have a 36-hour washout period if previously on an ACE inhibitor to avoid angioedema risk.
  • Entresto works through a dual mechanism - sacubitril inhibits neprilysin (increasing beneficial peptides like natriuretic peptides) while valsartan blocks angiotensin II receptors, together reducing cardiac workload and improving heart function.
  • Blood pressure, renal function, and potassium levels should be monitored during treatment.
  • The dose of Entresto typically starts at 24/26 mg twice daily and titrates up to 97/103 mg twice daily as tolerated.
  • The use of Entresto in patients with NSTEMI should be based on individual patient needs and clinical judgment, taking into account the potential benefits and risks of the medication 1.

From the Research

Entresto in NSTEMI

  • Entresto, also known as sacubitril/valsartan, is a medication used to treat heart failure and has been studied in the context of non-ST-segment elevation myocardial infarction (NSTEMI) 2, 3, 4.
  • A study published in the Journal of the American College of Cardiology found that sacubitril/valsartan did not significantly decrease the risk for cardiovascular death and heart failure in patients with acute myocardial infarction (AMI) complicated by left ventricular dysfunction, irrespective of the type of AMI (STEMI or NSTEMI) 2.
  • Another study published in the European journal of internal medicine highlighted the importance of managing heart failure in patients with NSTEMI, and noted that angiotensin-converting enzyme inhibitors have been shown to decrease the risk for cardiovascular events in these patients 5.
  • A review of contemporary NSTEMI management published in Hospital practice emphasized the importance of individualized patient risk assessment and evidence-based therapies, including anti-anginal, anticoagulant, and antiplatelet medications, to improve short- and long-term clinical outcomes 6.
  • The use of sacubitril/valsartan in heart failure has been associated with reduced risk of death from cardiovascular causes, heart failure hospitalizations, and all-cause mortality, as demonstrated in the PARADIGM-HF study 3, 4.

Key Findings

  • Sacubitril/valsartan may not provide additional benefits in reducing cardiovascular events in patients with NSTEMI compared to other treatments 2.
  • Heart failure is a common and meaningful complication in patients with NSTEMI, and requires careful management and further investigation to reach stronger evidence for clinical recommendations 5.
  • Individualized patient risk assessment and evidence-based therapies are crucial in managing NSTEMI and improving clinical outcomes 6.
  • Sacubitril/valsartan has been shown to reduce morbidity and mortality in patients with chronic, symptomatic heart failure with reduced ejection fraction (HFrEF) 3, 4.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Angiotensin Receptor-Neprilysin Inhibition in Patients With STEMI vs NSTEMI.

Journal of the American College of Cardiology, 2024

Research

Sacubitril/valsartan in heart failure: latest evidence and place in therapy.

Therapeutic advances in chronic disease, 2016

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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