What additional medication would be most appropriate to reduce the risk of worsening heart failure in a patient with heart failure with reduced ejection fraction (HFrEF) and current medications including Aspirin, Atorvastatin (Lipitor), Furosemide (Lasix), Lisinopril (Zestril), Metoprolol succinate (Toprol-XL), and Spironolactone (Aldactone)?

From the Guidelines

Dapagliflozin (Farxiga) or empagliflozin (Jardiance) would be the most appropriate addition to this patient's medication regimen. These SGLT2 inhibitors have demonstrated significant benefits in reducing heart failure hospitalizations and cardiovascular mortality in patients with HFrEF, regardless of diabetic status, as supported by the 2023 chronic coronary disease guideline-at-a-glance 1 and the 2024 ESC guidelines for the management of chronic coronary syndromes 1. The recommended starting dose for dapagliflozin is 10 mg once daily, while empagliflozin is typically started at 10 mg once daily and can be increased to 25 mg daily if tolerated.

The patient is already on guideline-directed medical therapy including an ACE inhibitor (lisinopril), beta-blocker (metoprolol succinate), and mineralocorticoid receptor antagonist (spironolactone), which forms the foundation of HFrEF treatment. Adding an SGLT2 inhibitor would provide complementary benefits through multiple mechanisms, including improved cardiac energetics, reduced cardiac preload and afterload, anti-inflammatory effects, and inhibition of the sodium-hydrogen exchanger.

When initiating an SGLT2 inhibitor, monitor for potential side effects including genital mycotic infections, urinary tract infections, and volume depletion. Consider reducing the dose of furosemide initially if the patient is euvolemic, as SGLT2 inhibitors have diuretic properties. Renal function should be assessed before starting therapy and periodically thereafter, though these medications have demonstrated renal protective effects in clinical trials, as noted in the 2025 standards of care in diabetes 1.

Key points to consider:

• SGLT2 inhibitors are recommended for patients with HFrEF to reduce the risk of heart failure hospitalization and cardiovascular death, regardless of diabetic status 1.
• The patient's current medication regimen, including an ACE inhibitor, beta-blocker, and mineralocorticoid receptor antagonist, provides a foundation for HFrEF treatment.
• Adding an SGLT2 inhibitor can provide additional benefits and is supported by recent guidelines and clinical trials 1.

From the FDA Drug Label

Sacubitril and valsartan tablets are indicated to reduce the risk of cardiovascular death and hospitalization for heart failure in adult patients with chronic heart failure and reduced ejection fraction.

The recommended starting dosage for adults is 49 mg/51 mg orally twice daily. The target maintenance dose is 97 mg/103mg orally twice daily.

The patient is currently taking Lisinopril (Zestril), an ACE inhibitor. According to the drug label, sacubitril and valsartan tablets are contraindicated with concomitant use of an angiotensin-converting enzyme (ACE) inhibitor. However, if switching from an ACE inhibitor to sacubitril and valsartan tablets, a washout period of 36 hours between administration of the two drugs is recommended.

Considering the patient's current medication regimen and the need to reduce the risk of worsening heart failure, sacubitril and valsartan tablets could be an appropriate option, but only after discontinuing the ACE inhibitor (Lisinopril) and allowing for the recommended washout period.

• Key considerations:
  • Discontinue Lisinopril (Zestril)
  • Allow for a 36-hour washout period
  • Initiate sacubitril and valsartan tablets at the recommended starting dose of 49 mg/51 mg orally twice daily
  • Titrate to the target maintenance dose of 97 mg/103mg orally twice daily, as tolerated by the patient 2, 2.

From the Research

Heart Failure with Reduced Ejection Fraction (HFrEF) Management

The patient in question has heart failure with reduced ejection fraction (HFrEF) and is currently asymptomatic. To reduce the risk of worsening heart failure, the following points should be considered:

• The patient's current medications include Aspirin, Atorvastatin (Lipitor), Furosemide (Lasix), Lisinopril (Zestril), Metoprolol succinate (Toprol-XL), and Spironolactone (Aldactone).
• Studies have shown that Sodium-glucose cotransporter 2 (SGLT2) inhibitors, such as empagliflozin, can reduce the risk of cardiovascular death or hospitalization for heart failure in patients with HFrEF, regardless of the presence or absence of diabetes 3, 4.
• The EMPEROR-Reduced trial demonstrated that empagliflozin reduced the combined risk of death, hospitalization for heart failure, or an emergent/urgent heart failure visit requiring intravenous treatment in patients with HFrEF 3.
• Another study published in The New England Journal of Medicine found that empagliflozin reduced the risk of cardiovascular death or hospitalization for worsening heart failure in patients with HFrEF, with or without diabetes 4.

Recommended Additional Medication

Based on the evidence, the most appropriate additional medication to reduce the risk of worsening heart failure in this patient would be:

• Empagliflozin, an SGLT2 inhibitor, which has been shown to reduce the risk of cardiovascular death or hospitalization for heart failure in patients with HFrEF, regardless of the presence or absence of diabetes 3, 4, 5.

Key Points to Consider

• The patient's ejection fraction is 40%, which is consistent with HFrEF.
• The patient is currently asymptomatic, but the goal is to reduce the risk of worsening heart failure.
• Empagliflozin has been shown to reduce the risk of cardiovascular death or hospitalization for heart failure in patients with HFrEF, regardless of the presence or absence of diabetes.
• The medication should be used in addition to the patient's current medications, which include Aspirin, Atorvastatin (Lipitor), Furosemide (Lasix), Lisinopril (Zestril), Metoprolol succinate (Toprol-XL), and Spironolactone (Aldactone) 3, 4, 5.