What medications have evidence to prevent recurrent hospitalization in patients with heart failure with reduced ejection fraction (HFrEF)?

Medications for Heart Failure with Reduced Ejection Fraction to Prevent Recurrent Hospitalization

ACE inhibitors, beta-blockers, mineralocorticoid receptor antagonists (MRAs), and sacubitril/valsartan are the cornerstone medications that have strong evidence for preventing recurrent hospitalization in patients with heart failure with reduced ejection fraction (HFrEF). These medications should be prescribed in a stepwise approach to optimize outcomes.

First-Line Medications

ACE Inhibitors

• Recommended for all symptomatic patients with HFrEF to reduce the risk of HF hospitalization and death (Class I, Level A) 1
• Provide 5-16% reduction in mortality risk 1
• Example: Enalapril has been shown to decrease hospitalization for heart failure by 30% in patients with HFrEF 2

Beta-Blockers

• Recommended in addition to an ACE inhibitor for all patients with stable, symptomatic HFrEF (Class I, Level A) 1
• Only use evidence-based beta-blockers: carvedilol, metoprolol succinate, and bisoprolol 1
• Should be initiated at low doses and gradually uptitrated to maximum tolerated doses
• Provide at least 20% reduction in mortality risk 1

Second-Line Medications

Mineralocorticoid Receptor Antagonists (MRAs)

• Recommended for patients with HFrEF who remain symptomatic despite treatment with an ACE inhibitor and beta-blocker (Class I, Level A) 1
• Examples: spironolactone, eplerenone
• Provide at least 20% reduction in mortality risk 1
• Important monitoring: Regular checks of serum potassium and renal function are essential

Sacubitril/Valsartan (ARNI)

• Recommended as a replacement for an ACE inhibitor to further reduce the risk of HF hospitalization and death in ambulatory patients with HFrEF who remain symptomatic despite optimal treatment with an ACE inhibitor, beta-blocker, and MRA (Class I, Level B) 1
• Superior to enalapril in reducing hospitalization for heart failure by 21% (p<0.001) 3
• FDA-approved to reduce the risk of cardiovascular death and hospitalization for heart failure in adult patients with chronic HFrEF 4
• Important precaution: Requires 36-hour washout period when switching from ACE inhibitor 4

Emerging Therapy

SGLT2 Inhibitors

• Dapagliflozin has been shown to reduce the risk of worsening heart failure (hospitalization or urgent visits requiring IV therapy) by 30% compared to placebo (HR 0.70,95% CI 0.59-0.83) 5
• Benefits observed regardless of diabetes status
• While not included in the 2016 ESC guidelines, more recent evidence supports their use in HFrEF

Treatment Algorithm

1. Initial therapy: Start ACE inhibitor and beta-blocker simultaneously for all patients with HFrEF
2. Add MRA: For patients who remain symptomatic despite ACE inhibitor and beta-blocker therapy
3. Replace ACE inhibitor with sacubitril/valsartan: For patients who remain symptomatic despite optimal treatment with ACE inhibitor, beta-blocker, and MRA
4. Consider SGLT2 inhibitor: Based on more recent evidence

Common Pitfalls to Avoid

1. Underdosing: Only 16.9% of eligible patients are prescribed ≥50% of target doses of guideline-directed medications at hospital discharge 6
2. Omitting MRAs: Less than half of eligible patients receive MRAs despite clear evidence of benefit 6
3. Failure to uptitrate: Medications are often initiated at low doses but not uptitrated to target doses
4. Inappropriate discontinuation: Continuing these medications during hospitalization for HF exacerbation is recommended in the absence of hemodynamic instability 1
5. Drug interactions: Avoid combining ACE inhibitors with ARBs and MRAs due to increased risk of renal dysfunction and hyperkalemia 1
6. Contraindicated medications: Diltiazem and verapamil are not recommended in HFrEF as they increase the risk of HF worsening and hospitalization 1

Monitoring and Follow-up

• Regular assessment of fluid status and symptoms
• Monitoring of renal function and electrolytes, particularly when using MRAs
• Gradual uptitration of medications to target doses as tolerated
• Evaluation of adherence to medication regimen

By implementing this evidence-based approach to medication management in HFrEF, clinicians can significantly reduce the risk of recurrent hospitalizations and improve patient outcomes.