Entresto (Sacubitril/Valsartan) and Heart Rate Effects
Entresto (sacubitril/valsartan) does not typically slow down heart rate as its primary mechanism of action, but it may indirectly reduce heart rate in some patients through its sympathoinhibitory effects and improved cardiac function. 1
Mechanism of Action and Heart Rate Effects
- Entresto is an angiotensin receptor-neprilysin inhibitor (ARNi) that combines valsartan (an angiotensin receptor blocker) with sacubitril (a neprilysin inhibitor) 2
- Unlike beta-blockers, which directly slow heart rate, Entresto's primary mechanism is not heart rate reduction 3
- However, research has demonstrated that Entresto can reduce sympathetic nervous system activity, which may indirectly lead to modest heart rate reduction in some patients 1
- In a pilot study, sacubitril/valsartan reduced muscle sympathetic nerve activity (MSNA) burst frequency and burst incidence after two months of treatment, suggesting a sympathoinhibitory effect 1
Clinical Guidelines and Heart Rate Considerations
- Guidelines do not specifically list heart rate reduction as a primary effect or indication for Entresto 3
- For heart rate control in heart failure patients, particularly those with atrial fibrillation, beta-blockers and non-dihydropyridine calcium channel blockers are typically considered first-line agents 3
- In patients with heart failure with preserved ejection fraction (HFpEF) and atrial fibrillation, a recent trial (RATE-AF) showed that digoxin provided similar heart rate reduction compared to beta-blockers, with fewer adverse events such as dizziness, lethargy, and hypotension 3
Potential Side Effects Related to Heart Rate
- The most common cardiovascular side effect of Entresto is hypotension, not bradycardia 3
- Guidelines note that Entresto may cause "more symptomatic hypotension levels than valsartan" 3
- Monitoring blood pressure and renal function is recommended when using Entresto 3
- Starting dose adjustments are recommended in patients with renal impairment or moderate hepatic impairment 3
Clinical Implications
- Entresto has been shown to improve cardiac biomarkers, health status, and reverse cardiac remodeling processes regardless of heart failure duration 4
- Some research suggests Entresto may have potential antiarrhythmic effects, which could indirectly influence heart rate regulation 5
- In patients with both acute myocardial infarction and acute heart failure, Entresto has demonstrated improvements in clinical symptoms, ventricular remodeling, and reduced hospitalization rates 6
Important Considerations
- When transitioning to Entresto from an ACE inhibitor, a 36-hour washout period is required to avoid angioedema risk 3
- Entresto is contraindicated with concomitant use of ACE inhibitors due to increased risk of angioedema 3
- Blood pressure monitoring is essential when initiating Entresto, particularly in patients with existing hypotension 3
- Entresto should be used with caution in patients with severe renal impairment (eGFR <30 mL/min) or moderate hepatic impairment 3
In summary, while Entresto is not primarily prescribed for heart rate reduction and does not directly slow heart rate like beta-blockers, it may have indirect effects on heart rate through sympathoinhibition and improved cardiac function in some patients with heart failure.