What is the recommended treatment for heart failure?

Treatment of Heart Failure

All patients with heart failure and reduced ejection fraction (HFrEF, LVEF ≤40%) should receive four foundational medication classes simultaneously: ACE inhibitors (or ARNi), beta-blockers, mineralocorticoid receptor antagonists, and SGLT2 inhibitors, as this combination reduces mortality and hospitalization. 1

Initial Pharmacological Approach for HFrEF

ACE Inhibitors (First Pillar)

• Start ACE inhibitors immediately in all patients with reduced left ventricular systolic function, beginning with low doses and gradually titrating to target maintenance doses proven effective in clinical trials 2, 1, 3
• Target doses from major trials: lisinopril 20-35 mg daily, enalapril 10-20 mg twice daily, or ramipril 5-10 mg daily 1
• Before initiating ACE inhibitors, review and potentially reduce diuretic doses for 24 hours to avoid excessive hypotension 1
• Monitor blood pressure, renal function, and electrolytes 1-2 weeks after each dose increment, at 3 months, and subsequently at 6-month intervals 2, 1, 3
• Avoid NSAIDs and potassium-sparing diuretics during initiation 4

Beta-Blockers (Second Pillar - Mandatory Co-Therapy)

• Initiate beta-blockers in all stable patients with mild, moderate, and severe heart failure (NYHA class II-IV) who are already on ACE inhibitors and diuretics 4, 2, 3
• Evidence-based beta-blockers with proven mortality benefit: bisoprolol (target 10 mg daily), metoprolol succinate CR (target 200 mg daily), carvedilol (target 50 mg daily), or nebivolol (target 10 mg daily) 1
• Start with very low doses (bisoprolol 1.25 mg, metoprolol 12.5-25 mg, carvedilol 3.125 mg) and double every 1-2 weeks if tolerated 1
• Beta-blockers reduce mortality by at least 20% and decrease hospitalizations 1
• Ensure the patient has no intravenous inotropic support requirements or marked fluid retention before initiation 1

Mineralocorticoid Receptor Antagonists (Third Pillar)

• Add spironolactone or eplerenone for patients who remain symptomatic (NYHA Class III-IV) despite ACE inhibitor and beta-blocker therapy to reduce mortality and hospitalization 4, 1, 3
• Start at 12.5-25 mg daily only if serum potassium <5.0 mmol/L and creatinine <250 μmol/L 1
• Monitor serum potassium and creatinine carefully after 5-7 days and titrate accordingly, rechecking every 5-7 days until potassium values are stable 4, 2

SGLT2 Inhibitors (Fourth Pillar)

• Initiate SGLT2 inhibitors early in all HFrEF patients regardless of diabetes status to reduce cardiovascular death and heart failure hospitalization 1, 5
• SGLT2 inhibitors are also first-line treatment for patients with HF with mildly reduced ejection fraction or HF with preserved ejection fraction 5

Angiotensin Receptor-Neprilysin Inhibitor (ARNi) Upgrade

• Replace ACE inhibitor with sacubitril/valsartan in ambulatory patients with HFrEF who remain symptomatic despite optimal treatment with an ACE inhibitor, beta-blocker, and MRA 3, 6
• In the PARADIGM-HF trial, sacubitril/valsartan reduced the combined endpoint of cardiovascular death or hospitalization for heart failure (HR 0.8; 95% CI 0.73-0.87, p<0.0001) and improved overall survival (HR 0.84; 95% CI 0.76-0.93, p=0.0009) compared to enalapril 6

Diuretic Therapy for Symptom Relief

• Diuretics are essential for symptomatic treatment when fluid overload is present (pulmonary congestion or peripheral edema) and should always be administered in combination with ACE inhibitors 4, 2, 3
• Start with loop diuretics or thiazides; if GFR <30 ml/min, do not use thiazides except synergistically with loop diuretics 4, 2
• For insufficient response: increase diuretic dose, combine loop diuretics and thiazides, or administer loop diuretics twice daily 4
• In severe chronic heart failure with persistent fluid retention, add metolazone with frequent measurement of creatinine and electrolytes 4

Device Therapy

Implantable Cardioverter Defibrillators (ICDs)

• ICDs are recommended for primary prevention in symptomatic HF (NYHA Class II-III) with LVEF ≤35% despite ≥3 months of optimal medical therapy in patients with ischemic heart disease or dilated cardiomyopathy 1, 3
• ICDs are indicated for secondary prevention in patients who survived ventricular arrhythmia causing hemodynamic instability 1, 3
• Common pitfall: ICD implantation is not recommended within 40 days of an MI as it does not improve prognosis 3

Cardiac Resynchronization Therapy (CRT)

• CRT is recommended for symptomatic heart failure patients in sinus rhythm with QRS duration ≥150 msec, LBBB QRS morphology, and LVEF ≤35% 3

Non-Pharmacological Management

Patient Education and Self-Management

• Provide education about heart failure, symptom recognition, what to do if symptoms occur, and the importance of adhering to pharmacological and non-pharmacological prescriptions 4, 2, 1
• Teach self-weighing to monitor fluid status 4

Exercise and Physical Activity

• Recommend daily physical activity in stable patients to prevent muscle deconditioning and improve exercise tolerance 4, 2, 1, 3
• Exercise training programs are beneficial for stable NYHA II-III patients 4
• Rest is not encouraged in stable conditions 4

Dietary Modifications

• Control sodium intake when necessary, especially in patients with severe heart failure 4, 2, 1, 3
• Avoid excessive fluid intake in severe heart failure 4, 2, 1, 3
• Avoid excessive alcohol intake 4
• Refrain from smoking; use nicotine replacement therapies if needed 4

Critical Monitoring and Common Pitfalls

• Avoid diltiazem or verapamil in patients with HFrEF as they increase the risk of heart failure worsening 3
• Avoid the combination of an ACE inhibitor, ARB, and MRA due to increased risk of renal dysfunction and hyperkalemia 3
• When starting ACE inhibitors, avoid excessive diuresis before treatment and consider reducing or withholding diuretics for 24 hours 4, 1
• If renal function deteriorates substantially during ACE inhibitor initiation, stop treatment 4
• For heart failure patients experiencing symptomatic bradycardia on beta-blockers, reduce the dose 7
• If transient worsening of heart failure occurs during beta-blocker titration, treat with increased doses of diuretics and consider temporarily lowering or discontinuing the beta-blocker until symptoms stabilize 7