Should I hold Dapaliflozin (Forxiga) or Entresto (sacubitril/valsartan) in a patient with hypotension?

From the Guidelines

In a patient with hypotension, it is generally recommended to hold Entresto (sacubitril/valsartan) temporarily until blood pressure stabilizes, whereas Dapaliflozin (Forxiga) may be continued with caution, as the primary concern is addressing the underlying cause of hypotension rather than immediately discontinuing evidence-based therapies 1. When managing a patient with hypotension who is taking Dapaliflozin or Entresto, it is crucial to first identify and address any reversible causes of hypotension, such as over-diuresis, use of non-CV drugs with hemodynamic effects, autonomic dysfunction, or simultaneous administration of multiple HF medications.

• The decision to hold or continue these medications should be guided by clinical judgment, considering the severity of hypotension, the patient's symptoms, and their underlying condition.
• Entresto, being a more potent blood pressure-lowering agent, may need to be held temporarily if systolic blood pressure falls below 100 mmHg, and reassessed after blood pressure improves.
• Dapaliflozin, while having a less direct hypotensive effect, can contribute to volume depletion through its diuretic action, potentially worsening hypotension, but its benefits in heart failure patients often outweigh the risks, and it may be continued with close monitoring.
• The goal should be temporary interruption of these medications rather than permanent discontinuation, as both provide important cardiovascular and renal benefits in heart failure patients.
• Close monitoring of blood pressure, renal function, and electrolytes is essential when managing patients on these medications, especially during episodes of hypotension, and when restarting them after such episodes 1.

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 tablets. Permanent discontinuation of therapy is usually not required.

For Entresto (sacubitril/valsartan), if hypotension occurs, consider dose adjustment of diuretics, concomitant antihypertensive drugs, and treatment of other causes of hypotension. If hypotension persists, reduce the dosage or temporarily discontinue Entresto tablets.

There is no information about Dapaliflozin (Forxiga) in the provided drug labels, so no conclusion can be drawn for Dapaliflozin. 2 2

From the Research

Considerations for Holding Dapaliflozin or Entresto in Hypotensive Patients

• When considering whether to hold Dapaliflozin (Forxiga) or Entresto (sacubitril/valsartan) in a patient with hypotension, it's essential to understand the effects of these medications on blood pressure.
• Dapagliflozin has been shown to lower blood pressure in both hypertensive and non-hypertensive patients with type 2 diabetes, with a modest reduction in blood pressure compared to placebo 3.
• Entresto, on the other hand, has been studied in patients with acute myocardial infarction and acute heart failure, and has been shown to improve clinical symptoms, ventricular remodeling, and reduce hospitalization rates 4.
• In patients with heart failure with reduced ejection fraction (HFrEF), the use of dapagliflozin and sacubitril/valsartan together has been shown to be efficacious and safe, with no significant increase in the risk of hypovolemia 5.
• Additionally, the use of SGLT2 inhibitors or ARNI (such as Entresto) has been associated with a lower risk of atherosclerotic cardiovascular disease in patients with coexisting diabetes and heart failure 6.
• It's also important to note that dapagliflozin has been shown to reduce the risk of heart failure and mortality in patients with type 2 diabetes mellitus, particularly in those with HFrEF 7.

Potential Risks and Benefits

• The potential benefits of continuing Dapaliflozin or Entresto in a hypotensive patient must be weighed against the potential risks, including the risk of worsening hypotension.
• However, the available evidence suggests that these medications can be safely used together, and that the benefits of continued use may outweigh the risks in patients with heart failure and diabetes.
• Ultimately, the decision to hold or continue Dapaliflozin or Entresto in a hypotensive patient should be made on a case-by-case basis, taking into account the individual patient's clinical status and medical history.