What is the most appropriate intervention to reduce the risk of cardiovascular death or hospitalization for heart failure (HF) in a patient with heart failure with preserved ejection fraction (HFpEF) and hypertension, currently receiving candesartan (Angiotensin II receptor antagonist) and furosemide (Loop diuretic)?

Management of Heart Failure with Preserved Ejection Fraction: Adding Empagliflozin

Adding empagliflozin 10 mg once daily is the most appropriate intervention to reduce the risk of cardiovascular death or hospitalization for heart failure in this patient with HFpEF and hypertension.

Evidence Supporting Empagliflozin in HFpEF

SGLT2 inhibitors, particularly empagliflozin, have demonstrated significant benefits in patients with heart failure with preserved ejection fraction (HFpEF), regardless of diabetes status:

• The EMPEROR-Preserved trial showed that empagliflozin 10 mg daily reduced the composite of cardiovascular death or hospitalization for heart failure by 21% (HR 0.79 [95% CI 0.69–0.90]; P < 0.001) in patients with HFpEF (LVEF >40%) 1
• This benefit was consistent in patients with or without diabetes 2
• The 2024 ESC guidelines specifically recommend SGLT2 inhibitors (dapagliflozin or empagliflozin) for patients with HFpEF to reduce the risk of HF hospitalization or cardiovascular death (Class I, Level A recommendation) 2

Assessment of Other Proposed Interventions

Switching candesartan to losartan

• Not recommended as candesartan is an appropriate ARB for HFpEF
• ARBs are indicated for symptomatic patients with heart failure who don't tolerate ACEIs 2
• No evidence suggests losartan would provide superior outcomes compared to candesartan in this patient

Adding carvedilol

• While beta-blockers are beneficial in heart failure with reduced ejection fraction (HFrEF), there is insufficient evidence supporting their use specifically to reduce mortality or hospitalization in HFpEF
• Beta-blockers are indicated primarily for HFrEF patients 2

Adding spironolactone

• While mineralocorticoid receptor antagonists (MRAs) like spironolactone are beneficial in HFrEF, the evidence for their use in HFpEF is less robust than for SGLT2 inhibitors
• MRAs are indicated primarily for symptomatic patients with HFrEF who remain symptomatic despite treatment with ACEIs and beta-blockers 2

Implementation of Empagliflozin Therapy

When adding empagliflozin to this patient's regimen:

1. Start with empagliflozin 10 mg once daily 2, 1

2. Monitor for potential side effects:

   • Genital and urinary tract infections
   • Hypotension (especially given concurrent diuretic therapy)
   • Volume depletion

3. Continue current medications:

   • Maintain candesartan 8 mg once daily for hypertension control
   • Continue furosemide 40 mg daily for volume management

Expected Benefits

The addition of empagliflozin can provide several benefits:

• Reduced risk of cardiovascular death or hospitalization for heart failure 2, 1
• Improved clinical stability 3
• Reduced total number of heart failure hospitalizations 1
• Benefits typically appear early (within days to weeks) after initiation 3, 4

Monitoring Recommendations

• Monitor renal function and electrolytes at baseline and periodically
• Assess for signs of volume depletion, especially given concurrent diuretic therapy
• Follow blood pressure regularly, as empagliflozin may have additive hypotensive effects
• Evaluate for improvement in heart failure symptoms

Conclusion

Based on the most recent and highest quality evidence, adding empagliflozin 10 mg once daily is the optimal choice for this 45-year-old female with HFpEF and hypertension to reduce her risk of cardiovascular death or hospitalization for heart failure. The EMPEROR-Preserved trial provides strong evidence supporting this recommendation, with consistent benefits observed regardless of diabetes status.