From the Guidelines
Bradycardia is a potential risk in patients taking Entresto (sacubitril/valsartan), particularly in those with pre-existing conduction disorders or taking other heart rate-lowering medications, and healthcare providers should monitor heart rate and blood pressure regularly during therapy. According to the 2022 AHA/ACC/HFSA guideline for the management of heart failure 1, true contraindications to oral guideline-directed medical therapy (GDMT) are rare, such as advanced degree atrioventricular block for beta blockers in the absence of pacemakers. Patients with marked volume overload or marginal low cardiac output may require withholding or reducing beta-blocker therapy. The guideline also emphasizes that oral GDMT should not be withheld for mild or transient reductions in blood pressure or mild deteriorations in renal function.
In the context of Entresto, which is an angiotensin receptor-neprilysin inhibitor (ARNI), the risk of bradycardia may be increased due to its mechanism of action, which enhances the effects of natriuretic peptides and blocks angiotensin II, affecting heart rate regulation. Symptoms of bradycardia may include dizziness, fatigue, weakness, shortness of breath, or syncope, and patients should seek medical attention promptly if these occur.
Key considerations for managing bradycardia risk in patients taking Entresto include:
- Monitoring heart rate and blood pressure regularly during therapy
- Adjusting dosage or changing medications if significant bradycardia develops
- Informing healthcare providers about all medications being taken to minimize the risk of drug interactions that could worsen bradycardia
- Being aware of the potential for increased bradycardia risk in patients with pre-existing conduction disorders or taking other heart rate-lowering medications.
Overall, while bradycardia is a potential risk in patients taking Entresto, careful monitoring and management can help minimize this risk and ensure the benefits of Entresto therapy are realized, particularly in patients with heart failure, as supported by the 2022 AHA/ACC/HFSA guideline 1.
From the Research
Risks of Bradycardia in Patients Taking Entresto
The risks of bradycardia in patients taking Entresto (sacubitril/valsartan) include:
- Hypotension: Entresto can cause a decrease in blood pressure, which can lead to hypotension and bradycardia 2
- Renal dysfunction: Entresto can also cause renal dysfunction, which can increase the risk of bradycardia 2
- Ventricular arrhythmias: While Entresto has been shown to reduce the risk of ventricular arrhythmias and sudden cardiac death in patients with heart failure with reduced ejection fraction, it is not clear if it increases the risk of bradycardia 3
- Interaction with other medications: Entresto can interact with other medications, such as beta blockers, which can increase the risk of bradycardia 4
Factors that Increase the Risk of Bradycardia
Certain factors can increase the risk of bradycardia in patients taking Entresto, including:
- Lower mean arterial pressure: Patients with lower mean arterial pressure are more likely to experience bradycardia while taking Entresto 2
- Lower serum chloride: Patients with lower serum chloride levels are more likely to experience bradycardia while taking Entresto 2
- Presence of an implantable cardioverter-defibrillator and/or cardiac resynchronization device: Patients with these devices are more likely to experience bradycardia while taking Entresto 2
- Nonuse of angiotensin-converting enzyme inhibitor or angiotensin receptor blocker at the screening visit: Patients who are not taking these medications are more likely to experience bradycardia while taking Entresto 2
- Use of insulin at screening: Patients who are taking insulin are more likely to experience bradycardia while taking Entresto 2
Treatment of Bradycardia
Atropine can be used to treat hemodynamically unstable bradycardia and atrioventricular block, including in patients taking Entresto 5. However, the efficacy of atropine in patients taking Entresto is not well established.