Can Entresto (sacubitril/valsartan) cause bradycardia?

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Does Entresto Cause Bradycardia?

Entresto (sacubitril/valsartan) is not directly associated with causing bradycardia based on available evidence. The provided guidelines and research do not identify bradycardia as a recognized adverse effect of this medication.

Evidence Analysis

Direct Evidence on Entresto and Bradycardia

  • No documented bradycardia risk: The available research on sacubitril/valsartan does not list bradycardia among its adverse effects or safety concerns 1, 2, 3.

  • Clinical trial safety data: Meta-analyses and clinical trials examining Entresto have focused on arrhythmias like atrial fibrillation and atrial flutter, but bradycardia has not emerged as a significant concern 3.

  • Mechanism of action: Entresto works through angiotensin receptor blockade (valsartan) and neprilysin inhibition (sacubitril), neither of which directly affects heart rate or conduction system function in a way that would cause bradycardia 2.

Drugs That DO Cause Bradycardia

For context, medications with well-established bradycardia risk include:

  • Beta-blockers: Cause bradycardia through SA and AV nodal effects 4.

  • Nondihydropyridine calcium channel blockers (diltiazem, verapamil): Produce bradycardia and AV block 4.

  • Digoxin: Can cause bradyarrhythmias, particularly in toxicity 4.

  • Amiodarone and sotalol: Associated with bradycardia requiring pacemaker implantation 4.

  • Ivabradine: Specifically designed to slow heart rate, with excess bradycardia as a known risk when combined with other rate-lowering agents 4.

Important Clinical Considerations

  • Hypotension, not bradycardia: The main cardiovascular concern with Entresto is hypotension, particularly in patients with systolic blood pressure ≤100 mmHg, which is a contraindication for initiation 5.

  • Combination therapy caution: If a patient on Entresto is also taking beta-blockers or other rate-controlling medications (common in heart failure management), bradycardia could occur from those agents, not from Entresto itself 4.

  • No conduction system effects: Unlike drugs that affect SA or AV nodal function, Entresto does not have direct chronotropic or dromotropic effects 1.

References

Research

Sacubitril/valsartan: An antiarrhythmic drug?

Journal of cardiovascular electrophysiology, 2022

Research

Entresto, a New Panacea for Heart Failure?

Cardiovascular & hematological agents in medicinal chemistry, 2018

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

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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