Should a patient with hypotension skip a dose of Entresto (sacubitril/valsartan) for heart failure?

From the Guidelines

A patient with hypotension (MAP 68) should not skip a dose of Entresto (sacubitril/valsartan) without consulting their healthcare provider, as the benefits of continuing the medication for heart failure management often outweigh the risks associated with mild hypotension. According to the 2022 AHA/ACC/HFSA guideline for the management of heart failure 1, oral guideline-directed medical therapy (GDMT) should not be withheld for mild or transient reductions in blood pressure. This guideline emphasizes the importance of maintaining prescribed regimens for patients with heart failure to control symptoms and prevent disease progression.

Key Considerations

• The patient's current hypotension (MAP 68) may be a concern, but it is essential to weigh this against the benefits of Entresto in managing heart failure.
• The medication works by dilating blood vessels and reducing strain on the heart, which can lower blood pressure as part of its therapeutic effect.
• Patients with heart failure on Entresto should monitor their blood pressure regularly and keep a record to share with their healthcare provider.
• If hypotension becomes symptomatic or severe, temporary dose reduction or interruption may be necessary under medical supervision.

Guidance from Recent Studies

The 2022 AHA/ACC/HFSA guideline 1 and the 2012 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 1 both emphasize the importance of careful management of heart failure medications, including considerations for hypotension. However, they also highlight that the benefits of these medications often outweigh the risks, especially when it comes to controlling heart failure symptoms and preventing progression of the disease.

Recommendations

• Patients should not abruptly stop taking Entresto without medical guidance, as sudden discontinuation could worsen heart failure symptoms.
• Regular monitoring of blood pressure and symptoms is crucial for patients on Entresto.
• Healthcare providers should be consulted for guidance on managing hypotension in the context of Entresto treatment for heart failure.

From the FDA Drug Label

5.3 Hypotension Sacubitril and valsartan lowers blood pressure and may cause symptomatic hypotension [see Adverse Reactions (6. 1)]. Patients with an activated renin-angiotensin system, such as volume- and/or salt-depleted patients (e.g., those being treated with high doses of diuretics), are at greater risk. Correct volume or salt depletion prior to administration of sacubitril and valsartan or start at a lower dose. If hypotension occurs, consider dose adjustment of diuretics, concomitant antihypertensive drugs, and treatment of other causes of hypotension (e.g., hypovolemia). If hypotension persists despite such measures, reduce the dosage or temporarily discontinue sacubitril and valsartan.

Hypotension Management: If a patient with heart failure taking Entresto (sacubitril/valsartan) twice daily experiences low blood pressure (MAP 68), the management approach includes:

• Correcting volume or salt depletion
• Adjusting the dose of diuretics or concomitant antihypertensive drugs
• Treating other causes of hypotension
• Considering a reduction in dosage or temporary discontinuation of sacubitril and valsartan if hypotension persists 2 It is recommended to temporarily discontinue or reduce the dosage of Entresto in patients with symptomatic hypotension.

From the Research

Hypotension and Entresto (Sacubitril/Valsartan) Use

• Entresto (sacubitril/valsartan) is a medication used to treat heart failure with reduced ejection fraction (HFrEF) 3, 4.
• It has been shown to reduce mortality and hospitalization rates in patients with HFrEF compared to enalapril 3, 4.
• However, one of the potential side effects of Entresto is hypotension (low blood pressure) 4, 5.

Management of Hypotension in Patients Taking Entresto

• A study published in the Journal of the American College of Cardiology found that patients who experienced symptomatic hypotension while taking Entresto were at higher risk for adverse outcomes, but the benefits of Entresto were maintained in these patients 5.
• The study suggested that the occurrence of hypotension during treatment with Entresto or enalapril was associated with worse outcomes, but the benefits of Entresto were not diminished in patients experiencing hypotension 5.
• Another study published in Pharmacology Research & Perspectives found that Entresto increased the risk of symptomatic hypotension in patients with HFrEF, but the evidence was of low quality 4.

Skipping a Dose of Entresto Due to Low Blood Pressure

• There is no clear guidance on whether a patient with hypotension should skip a dose of Entresto 3, 4, 5, 6.
• However, it is generally recommended that patients with heart failure work closely with their healthcare provider to manage their condition and adjust their medication regimen as needed 3, 4.
• Patients with low blood pressure (MAP 68) who are taking Entresto should consult their healthcare provider for guidance on managing their condition and adjusting their medication regimen if necessary 5.