From the Guidelines
No, a patient with cardiomyopathy and an ejection fraction of 25-30% should not reduce Entresto (sacubitril/valsartan) from twice daily to once daily due to fatigue. Entresto is specifically designed to be taken twice daily to maintain consistent blood levels of the medication throughout the day, as indicated in the 2022 AHA/ACC/HFSA guideline for the management of heart failure 1. Reducing to once daily dosing could significantly compromise the medication's effectiveness in managing heart failure and may lead to worsening of cardiac function. If fatigue is a concern, the patient should consult their cardiologist who might consider adjusting the dose while maintaining twice daily frequency, or investigating other causes of fatigue. The fatigue experienced might be related to the underlying heart condition rather than the medication itself. Some key points to consider in the management of heart failure with reduced ejection fraction (HFrEF) include:
- The importance of maintaining consistent blood levels of prescribed medications, such as Entresto, to ensure optimal cardiac function and reduce mortality risk.
- The potential for underlying heart conditions to contribute to symptoms like fatigue, rather than the medication itself.
- The need for close monitoring and adjustment of treatment regimens by a cardiologist to balance efficacy and tolerability. According to the guideline, the target dose for sacubitril-valsartan is 97 mg sacubitril and 103 mg valsartan twice daily, with a mean dose achieved in clinical trials of 182 mg sacubitril and 193 mg valsartan total daily 1. Proper adherence to the prescribed regimen is crucial for patients with reduced ejection fraction to prevent heart failure progression and reduce mortality risk. Entresto works by enhancing beneficial neurohormonal pathways while blocking harmful ones, helping to reduce strain on the heart and improve cardiac function over time. Therefore, it is essential to prioritize maintaining the prescribed twice-daily dosing regimen for Entresto, rather than reducing the frequency, to ensure optimal management of heart failure and minimize the risk of adverse outcomes.
From the FDA Drug Label
2.2 Adult Heart Failure The recommended starting dose of ENTRESTO is 49/51 mg orally twice-daily. Double the dose of ENTRESTO after 2 to 4 weeks to the target maintenance dose of 97/103 mg twice daily, as tolerated by the patient.
The FDA drug label does not provide guidance on reducing the frequency of Entresto from twice daily to once daily due to fatigue.
- Dosing frequency: The label recommends a twice-daily dosing regimen for adult heart failure patients.
- Dose adjustment: While the label allows for dose adjustment based on patient tolerance, it does not specify reducing the frequency as a solution for fatigue.
- Clinical decision: In the absence of direct guidance from the FDA label, a conservative clinical decision would be to consult with a healthcare professional to discuss potential alternatives or adjustments to the patient's treatment plan, rather than unilaterally changing the dosing frequency. 2 2
From the Research
Patient Request to Reduce Entresto Frequency
The patient is experiencing fatigue while taking Entresto (sacubitril/valsartan) twice daily for cardiomyopathy with an ejection fraction (EF) of 25-30%. The patient is asking to reduce the frequency to once daily.
Current Research on Entresto
- Studies have shown that Entresto is effective in improving heart failure outcomes, including reducing mortality and hospitalization rates 3, 4, 5.
- Entresto has been shown to improve left ventricular systolic and diastolic function in patients with heart failure with reduced ejection fraction (HFrEF) 4.
- The PARADIGM-HF trial demonstrated that sacubitril/valsartan significantly reduces HFrEF mortality and heart failure hospitalization rate 4.
Dosing Frequency
- There is no direct evidence to support reducing the frequency of Entresto from twice daily to once daily.
- The standard dosing regimen for Entresto is twice daily, and deviating from this regimen may affect its efficacy 5.
- However, some studies suggest that sacubitril/valsartan can be effective in improving heart failure outcomes even at lower doses or with less frequent administration 6, 7.
Considerations
- The patient's fatigue may be a side effect of Entresto, and reducing the frequency may alleviate this symptom.
- However, reducing the frequency may also reduce the efficacy of the medication, which could negatively impact the patient's heart failure outcomes.
- It is essential to weigh the potential benefits and risks of reducing the frequency of Entresto and to consider alternative strategies to manage the patient's fatigue, such as adjusting the dose or adding other medications 3, 4, 5.