What is the most appropriate adjustment to the treatment regimen to reduce the risk of heart failure rehospitalization and cardiovascular death in a patient with heart failure with reduced ejection fraction?

Empagliflozin is the Most Appropriate Addition to AF's Heart Failure Treatment Regimen

Starting empagliflozin 10 mg orally daily is the most appropriate change to AF's treatment regimen to reduce her risk of heart failure rehospitalization and cardiovascular death.

Rationale for Adding Empagliflozin

The patient is a 62-year-old female with heart failure with improved ejection fraction (LVEF 45%), currently experiencing NYHA Class II symptoms despite being on guideline-directed medical therapy including:

• Sacubitril/valsartan 49/51 mg twice daily
• Carvedilol 25 mg twice daily
• Furosemide 40 mg daily

Evidence Supporting SGLT2 Inhibitors in Heart Failure

SGLT2 inhibitors have demonstrated significant benefits in heart failure patients regardless of ejection fraction:

• The 2021 ACC Expert Consensus Decision Pathway recommends SGLT2 inhibitors (dapagliflozin or empagliflozin) as part of guideline-directed medical therapy for HFrEF 1.
• The 2024 ESC Guidelines for AF management strongly recommend SGLT2 inhibitors for patients with HF and AF regardless of LVEF to reduce the risk of HF hospitalization and cardiovascular death (Class I, Level A) 1.
• The 2022 AHA/ACC/HFSA Guidelines recommend SGLT2 inhibitors for patients with HF to reduce hospitalizations and mortality 1.

Benefits of Empagliflozin Specifically

Empagliflozin has shown particular benefits in clinical trials:

• In the EMPEROR-Reduced trial, empagliflozin significantly reduced the combined risk of death, hospitalization for heart failure, or urgent heart failure visits requiring IV treatment (HR 0.76; 95% CI, 0.67-0.87; P<0.0001) 2.
• Benefits of empagliflozin were seen as early as 12 days after initiation and were sustained throughout treatment 2.
• Empagliflozin reduced the total number of heart failure hospitalizations that required intensive care or vasopressor/inotropic support 2.

Why Other Options Are Not Optimal

Increasing Carvedilol Dose

• The patient is already on carvedilol 25 mg twice daily, which is the target dose for patients <85 kg 1.
• Increasing to 50 mg twice daily would only be appropriate if she weighed ≥85 kg, which she does not (78 kg).
• No evidence suggests further benefit from exceeding target doses of beta-blockers.

Increasing Furosemide Dose

• The patient has no signs of fluid overload (no edema or rales on examination).
• Increasing diuretic dose without evidence of congestion could lead to electrolyte abnormalities and hypotension.
• Diuretics manage symptoms but don't reduce mortality or hospitalization risk in euvolemic patients.

Starting Ivabradine

• Ivabradine is indicated for patients with HFrEF who have a resting heart rate ≥70 bpm despite maximum tolerated beta-blocker dose 3.
• This patient's heart rate is 69 bpm, just below the threshold for ivabradine initiation.
• The FDA label specifically indicates ivabradine for patients with LVEF ≤35%, while this patient has an LVEF of 45% 3.

Implementation Considerations

When initiating empagliflozin:

• Starting dose: 10 mg orally once daily 1
• Monitoring: Regular assessment of renal function and electrolytes
• Patient education: Inform about potential genital mycotic infections and urinary tract infections
• Maintain current therapy: Continue sacubitril/valsartan, carvedilol, and furosemide

Expected Benefits

Adding empagliflozin to the patient's regimen is expected to:

• Reduce risk of heart failure hospitalization by approximately 30%
• Potentially improve survival
• Reduce need for intensification of diuretics
• Provide benefits regardless of diabetes status

Conclusion

For this 62-year-old female with heart failure (LVEF 45%) and NYHA Class II symptoms, adding empagliflozin 10 mg daily to her current regimen is the most evidence-based approach to reduce her risk of heart failure rehospitalization and cardiovascular death.