What is the initial management for patients with heart failure, particularly those with reduced ejection fraction?

Initial Management of Heart Failure with Reduced Ejection Fraction

Start four foundational medication classes simultaneously at low doses in all patients with HFrEF: SGLT2 inhibitor, mineralocorticoid receptor antagonist (MRA), beta-blocker, and renin-angiotensin system (RAS) inhibitor, with gradual titration over 6-12 weeks while adding loop diuretics only if fluid overload is present. 1

First-Line Medication Regimen

Immediate Initiation (Start All Four Classes)

SGLT2 Inhibitor - Start first as it has minimal blood pressure impact while providing significant mortality benefit 1:

• Dapagliflozin 10 mg daily OR empagliflozin 10 mg daily 1
• Can be initiated during hospitalization for acute decompensated heart failure 1
• Do NOT defer to outpatient setting - in-hospital initiation reduces early post-discharge mortality 1
• Contraindicated if eGFR <30 mL/min/1.73m² 1

Mineralocorticoid Receptor Antagonist - Start simultaneously with SGLT2 inhibitor 1:

• Spironolactone 12.5-25 mg daily OR eplerenone 25 mg daily 1
• Requires eGFR >30 mL/min/1.73m² and serum potassium <5.0 mEq/L 2, 3
• Reduces mortality by 30% in NYHA class III-IV patients 2
• Has minimal blood pressure effect, making it ideal for early initiation 1

Beta-Blocker - Initiate early, particularly if heart rate >70 bpm 1:

• Carvedilol, metoprolol succinate, or bisoprolol (only these three proven to prolong life) 4
• Start at low dose and titrate gradually 4, 1
• Reduces mortality by at least 20% and decreases sudden death risk 4

RAS Inhibitor - Start with ACE inhibitor as first choice 4, 1:

• ACE inhibitor (e.g., lisinopril starting at 2.5-5 mg daily) 5
• Consider sacubitril/valsartan instead of ACE inhibitor for superior outcomes 6
• If ACE inhibitor intolerant (cough, angioedema), use ARB 3
• Modest mortality benefit (5-16% risk reduction) compared to other classes 4

Diuretic Therapy for Symptom Control

Loop diuretics are NOT first-line therapy - only add if fluid retention is present 4:

• Use for rapid relief of dyspnea and peripheral edema 4
• Adjust dose based on volume status 4
• Reduce diuretic dose when initiating ACE inhibitors to prevent excessive hypotension 4
• No proven survival benefit, purely symptomatic treatment 4

Titration Strategy

Use a rapid sequential approach rather than waiting to reach target doses 1, 7:

• Start all four foundational medications at low doses simultaneously 1
• Titrate gradually to target doses over 6-12 weeks 1, 6
• Target doses from trials: often not achieved, and benefits occur even at sub-target doses 7
• Early benefits obtained with even low doses of most therapies 7

For patients with low blood pressure at baseline 1:

• Prioritize SGLT2 inhibitor and MRA first (least BP effect) 1
• Then add beta-blocker if heart rate >70 bpm 1
• Finally add ACE inhibitor/ARB/ARNI at low dose 1

Monitoring Requirements

Check renal function and electrolytes frequently 4, 1:

• At 1-2 weeks after initiation and each dose increment 4, 1
• At 3 months, then every 6 months thereafter 6
• Monitor blood pressure, heart rate, and symptoms at each visit 6

Stop ACE inhibitor/ARB/ARNI if 4:

• Renal function deteriorates substantially 4
• Serum creatinine >2.5 mg/dL in men or >2.0 mg/dL in women 3
• Serum potassium >5.0 mEq/L (reduce MRA dose first) 1, 3

Critical Pitfalls to Avoid

Do NOT delay SGLT2 inhibitor initiation - deferring exposes patients to excess early mortality risk 1

Do NOT use sequential monotherapy - waiting to reach target dose of one medication before starting another delays benefit 1

Avoid NSAIDs completely - they worsen renal function and counteract heart failure medication benefits 4, 6

Do NOT withhold therapy for asymptomatic low blood pressure - this compromises long-term outcomes 8

Avoid potassium-sparing diuretics during ACE inhibitor initiation - risk of hyperkalemia 4

Do NOT use most calcium channel blockers or antiarrhythmic drugs - they should be avoided or withdrawn 3

Additional Considerations

Sodium and fluid restriction 4:

• Sodium <2-3 g daily in severe heart failure 8
• Fluid restriction only if hyponatremia present 8

Patient education is essential 4:

• Daily weight monitoring 4, 8
• Recognition of worsening symptoms 4
• Medication adherence importance 4
• Smoking cessation 4

Exercise training recommended when clinically stable 4, 8, 3