What is the initial pharmacological management of heart failure?

Initial Pharmacological Management of Heart Failure

The initial pharmacological management of heart failure with reduced ejection fraction (HFrEF) should begin with an ACE inhibitor (or ARB if ACE inhibitor not tolerated) and a beta blocker, along with diuretics for symptomatic relief of fluid overload. 1, 2

First-Line Medications for HFrEF

ACE Inhibitors

• First-line therapy for all patients with HFrEF
• Start at low dose and gradually titrate to target doses
• Examples with initial/target doses:
  • Lisinopril: 2.5-5 mg once daily / 20-40 mg once daily
  • Enalapril: 2.5 mg twice daily / 10-20 mg twice daily
  • Captopril: 6.25 mg three times daily / 50 mg three times daily
• Monitor renal function and electrolytes at initiation, 1-2 weeks after dose increases, and periodically thereafter

Beta Blockers

• Should be initiated in all stable patients with HFrEF
• Only three beta blockers have proven mortality benefit 1:
  • Bisoprolol: 1.25 mg once daily / 10 mg once daily
  • Carvedilol: 3.125 mg twice daily / 25-50 mg twice daily
  • Metoprolol succinate: 12.5-25 mg once daily / 200 mg once daily
• Start at low dose and double every 2-4 weeks as tolerated
• High-quality evidence shows that ACE inhibitors and beta blockers reduce morbidity and increase survival in patients with left ventricular systolic dysfunction 1

Diuretics

• Essential for symptomatic treatment of fluid overload
• Loop diuretics are preferred for most HF patients:
  • Furosemide: 20-40 mg once or twice daily / up to 600 mg daily
  • Bumetanide: 0.5-1.0 mg once or twice daily / up to 10 mg daily
  • Torsemide: 10-20 mg once daily / up to 200 mg daily
• Titrate dose based on symptoms, fluid status, and renal function
• Monitor electrolytes regularly, especially potassium and sodium

Second-Line Medications

Mineralocorticoid Receptor Antagonists (MRAs)

• Add for patients with NYHA class II-IV symptoms and LVEF ≤35% 1
• Options:
  • Spironolactone: 12.5-25 mg once daily / 25-50 mg once daily
  • Eplerenone: 25 mg once daily / 50 mg once daily
• Monitor potassium and renal function closely
• Avoid if creatinine >2.5 mg/dL in men or >2.0 mg/dL in women, or if K+ >5.0 mEq/L

Angiotensin Receptor Neprilysin Inhibitor (ARNI)

• Sacubitril/valsartan can replace ACE inhibitor in patients who remain symptomatic despite optimal therapy 1, 3
• Initial dose: 49/51 mg twice daily; target dose: 97/103 mg twice daily
• Provides 16% relative risk reduction in all-cause mortality compared to ACE inhibitors 1
• Requires 36-hour washout period after discontinuing ACE inhibitor

SGLT2 Inhibitors

• Newer addition to HF therapy with mortality benefit
• Options:
  • Dapagliflozin: 10 mg once daily
  • Empagliflozin: 10 mg once daily
• Monitor for genital infections, volume depletion, and ketoacidosis

Special Considerations

ARBs as Alternative to ACE Inhibitors

• Use when ACE inhibitors cause intolerable cough or angioedema
• Options:
  • Candesartan: 4-8 mg once daily / 32 mg once daily
  • Losartan: 25-50 mg once daily / 50-150 mg once daily
  • Valsartan: 20-40 mg once daily / 160 mg twice daily

Hydralazine and Isosorbide Dinitrate

• Consider for patients who cannot tolerate ACE inhibitors or ARBs
• Particularly beneficial in African American patients 1
• Fixed-dose combination: 20 mg isosorbide dinitrate/37.5 mg hydralazine three times daily, titrated to 40 mg/75 mg three times daily

Treatment Algorithm

1. Initial Assessment:

   • Confirm diagnosis with echocardiography and natriuretic peptide levels
   • Determine LVEF to guide therapy (HFrEF vs. HFpEF)
   • Assess volume status, blood pressure, and renal function

2. Start Core Medications for HFrEF:

   • ACE inhibitor (or ARB if not tolerated) at low dose
   • Beta blocker at low dose (if hemodynamically stable)
   • Diuretic if fluid overload present

3. Titration Phase:

   • Gradually increase ACE inhibitor/ARB to target dose over 2-4 weeks
   • Once ACE inhibitor/ARB at stable dose, uptitrate beta blocker every 2 weeks
   • Adjust diuretic dose based on symptoms and fluid status

4. Add Additional Therapy if Symptomatic:

   • Add MRA if LVEF ≤35% and NYHA class II-IV
   • Consider ARNI to replace ACE inhibitor if still symptomatic
   • Add SGLT2 inhibitor regardless of diabetes status
   • Consider hydralazine/isosorbide dinitrate, especially in African American patients

Common Pitfalls to Avoid

1. Underdosing medications: Always aim for target doses used in clinical trials unless limited by side effects.

2. Stopping beta blockers during mild exacerbations: Reduce dose temporarily rather than discontinuing.

3. Inadequate monitoring: Follow electrolytes and renal function closely, especially after initiation or dose changes.

4. Failure to recognize and treat congestion: Inadequate diuresis can limit the tolerability of disease-modifying therapies.

5. Using medications with negative effects: Avoid non-dihydropyridine calcium channel blockers, most antiarrhythmics, and NSAIDs in HFrEF patients.

6. Delaying initiation of key therapies: The mortality benefit of these medications is greatest when started early in the disease course.

By following this evidence-based approach to pharmacological management of heart failure, clinicians can significantly reduce mortality, hospitalization rates, and improve quality of life for patients with HFrEF.