What are the recommended medications for treating heart failure?

Recommended Medications for Heart Failure

The cornerstone medications for heart failure treatment are ACE inhibitors and beta-blockers, which should be initiated in all patients with heart failure with reduced ejection fraction (HFrEF) to reduce mortality and morbidity, with additional therapies added based on symptom severity and clinical status. 1

First-Line Therapy

ACE Inhibitors

• Start with low dose and gradually titrate up to target doses
• Initial dose of lisinopril: 5 mg daily for heart failure 2
• Maximum dose: 40 mg daily 2
• Monitor blood pressure, renal function, and electrolytes 1-2 weeks after each dose increment 1
• Avoid NSAIDs during treatment 3
• Avoid potassium-sparing diuretics during initiation 3

Beta-Blockers

• Recommended for all stable patients with HFrEF in NYHA class II-IV already on ACE inhibitors and diuretics 3, 1
• Start with very low dose and titrate gradually 1
• Only initiate when patient is in stable condition without need for intravenous inotropic therapy 3
• Monitor for worsening heart failure symptoms, fluid retention, hypotension, and bradycardia during titration 3

Second-Line Therapy

Mineralocorticoid Receptor Antagonists (MRAs)

• Add spironolactone for advanced heart failure (NYHA III-IV) 3, 1
• Indicated for NYHA Class III-IV heart failure with reduced ejection fraction 4
• Improves survival and reduces hospitalization 4
• Monitor potassium and renal function closely, especially when combined with ACE inhibitors 3

Angiotensin Receptor Blockers (ARBs)

• Consider for patients who cannot tolerate ACE inhibitors due to cough 3, 1
• May improve symptoms and reduce hospitalizations when combined with ACE inhibitors 3
• Note: Effectiveness for mortality reduction compared to ACE inhibitors is not clearly established 1

Angiotensin Receptor-Neprilysin Inhibitor (ARNI)

• Consider sacubitril/valsartan to replace ACE inhibitors in patients who remain symptomatic despite optimal treatment with ACE inhibitor, beta-blocker, and MRA 1
• Shows greater reduction in mortality and hospitalization compared to ACE inhibitors alone 1

Diuretics

• Primarily for symptomatic relief of congestion 1
• Loop diuretics (e.g., furosemide) preferred for HFrEF 1
• Thiazides only if GFR >30 mL/min 3, 1
• For insufficient response: increase dose, combine loop diuretics and thiazides, or administer loop diuretics twice daily 3
• In severe heart failure with persistent fluid retention, consider adding metolazone with frequent monitoring of creatinine and electrolytes 3

Cardiac Glycosides

• Indicated for atrial fibrillation with heart failure to control ventricular rate 3
• In sinus rhythm, digoxin can improve clinical status in patients with persistent symptoms despite ACE inhibitor and diuretic treatment 3
• Combination of digoxin and beta-blockade appears superior to either agent alone 3

Medication Titration Protocol

1. Initial Assessment:

   • Start with ACE inhibitor at low dose (e.g., lisinopril 5 mg daily) 2
   • If patient has hyponatremia (serum sodium <130 mEq/L), start at 2.5 mg daily 2

2. ACE Inhibitor Titration:

   • Increase dose gradually every 1-2 weeks as tolerated 1
   • Target maximum tolerated dose up to 40 mg daily 2
   • Monitor blood pressure, renal function, and electrolytes after each dose increase 3

3. Beta-Blocker Addition:

   • Add once patient is stable on ACE inhibitor 3
   • Start with very low dose and double every 1-2 weeks if tolerated 3
   • Monitor for bradycardia, hypotension, and worsening heart failure 3

4. MRA Addition:

   • Add spironolactone for patients with NYHA class III-IV symptoms 3, 4
   • Start with low dose and monitor potassium and renal function after 5-7 days 3

5. Diuretic Management:

   • Adjust diuretic dose based on congestion symptoms 1
   • Consider combination therapy for resistant fluid retention 3

Special Considerations

Renal Impairment

• For creatinine clearance ≥10 mL/min and ≤30 mL/min, reduce initial dose of lisinopril to half (2.5 mg) 2
• For patients on hemodialysis or creatinine clearance <10 mL/min, start with 2.5 mg once daily 2
• Avoid thiazide diuretics if GFR <30 mL/min except when prescribed synergistically with loop diuretics 3

Hypotension Management

• If hypotension occurs, first reduce the dose of vasodilators 3
• Reduce beta-blocker dose if necessary 3
• For systolic BP ≤100 mmHg, consider maintenance dose of 5 mg lisinopril 2

Medication Interactions

• Avoid NSAIDs in patients with heart failure 3, 1
• Do not combine an ARB with both an ACE inhibitor and an MRA due to increased risk of renal dysfunction and hyperkalemia 1
• Avoid diltiazem or verapamil in HFrEF as they increase risk of worsening heart failure 1

Common Pitfalls to Avoid

1. Underdosing of ACE inhibitors: Many physicians prescribe doses lower than those shown to reduce morbidity and mortality. The ATLAS study demonstrated that high doses of lisinopril (32.5-35 mg daily) were more effective than low doses (2.5-5 mg daily) in reducing hospitalizations and the combined endpoint of morbidity and mortality 5, 6

2. Failure to add beta-blockers: Beta-blockers should be added to ACE inhibitors even in patients with severe heart failure, as they significantly reduce mortality 3, 1

3. Inadequate monitoring: Regular monitoring of blood pressure, renal function, and electrolytes is essential, especially after dose increases 3, 1

4. Inappropriate discontinuation: Transient worsening of symptoms during titration should prompt adjustment of diuretics rather than discontinuation of ACE inhibitors or beta-blockers 3

5. Overlooking potassium levels: When using combinations of ACE inhibitors and MRAs, close monitoring of potassium is essential to prevent hyperkalemia 3