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 all four foundational medication classes simultaneously in patients with newly diagnosed HFrEF: SGLT2 inhibitors, ACE inhibitors (or ARNI/ARB), beta-blockers, and mineralocorticoid receptor antagonists, along with loop diuretics for symptomatic fluid overload. 1, 2

Immediate Medication Initiation Strategy

First-Line Therapy (Start These Together)

Begin with SGLT2 inhibitor and MRA on day one, as these have minimal blood pressure effects while providing significant mortality benefits: 1, 2

• SGLT2 inhibitor: Dapagliflozin 10 mg daily or empagliflozin 10 mg daily for all patients with eGFR >20-30 mL/min/1.73m² 1, 2
• MRA: Spironolactone 12.5-25 mg daily (start 25 mg if tolerated) for patients with NYHA Class III-IV symptoms and eGFR >30 mL/min/1.73m² 1, 3

Second-Line Additions (Within First Week)

Add ACE inhibitor and beta-blocker based on hemodynamic tolerance: 2

• ACE inhibitor: Start lisinopril 2.5-5 mg daily, enalapril 2.5 mg twice daily, or captopril 6.25 mg three times daily 4, 5
• Beta-blocker: Initiate if heart rate >70 bpm with bisoprolol 1.25 mg daily, carvedilol 3.125 mg twice daily, or metoprolol succinate 12.5-25 mg daily 2

Diuretic Therapy for Symptom Control

Use loop diuretics only for active fluid retention (pulmonary congestion or peripheral edema), not as routine therapy: 4

• Start furosemide 20-40 mg daily or equivalent, titrate to achieve euvolemia 4
• Reduce diuretic dose by 50% when initiating ACE inhibitor to prevent excessive hypotension 4
• Withhold diuretics for 24 hours before starting ACE inhibitor if patient is not volume overloaded 4

Titration Protocol

Uptitrate one medication at a time every 1-2 weeks to target doses proven effective in major trials: 2, 6

Target Doses (Titrate Gradually)

• ACE inhibitors: Lisinopril 20-40 mg daily, enalapril 10-20 mg twice daily, or ramipril 5 mg twice daily 5, 7
• Beta-blockers: Bisoprolol 10 mg daily, carvedilol 25-50 mg twice daily, or metoprolol succinate 200 mg daily 2
• MRA: Spironolactone 25-50 mg daily (most patients in trials received mean dose of 26 mg daily) 3
• SGLT2 inhibitors: No titration needed—use fixed dose 1

Important caveat: Target doses were goals based on tolerability in trials, and many patients benefited from sub-target doses—early mortality benefits occur even with low doses. 6

Critical Monitoring Parameters

Check these labs at baseline and 1-2 weeks after each medication change: 2

• Blood pressure and heart rate at every visit 2
• Serum potassium and creatinine (check 5-7 days after MRA initiation, then weekly until stable) 4, 2
• Complete metabolic panel including BUN, glucose 2
• Baseline: CBC, urinalysis, fasting lipids, liver function, TSH 2

Acceptable Parameters During Titration

• Systolic BP: Can tolerate 90-100 mmHg if asymptomatic and adequately perfused 2
• Potassium: 5.0-5.5 mEq/L acceptable; reduce MRA dose if >5.5 mEq/L 1
• Creatinine: Up to 30% increase acceptable; stop ACE inhibitor if >50% increase or creatinine >3.0 mg/dL 4, 5
• Heart rate: Target 60-70 bpm with beta-blocker 2

Medication Adjustment Algorithm for Low Blood Pressure

If symptomatic hypotension develops during titration (dizziness, lightheadedness, syncope): 2

If Heart Rate >70 bpm:

1. Reduce ACE inhibitor/ARB/ARNI dose first 2
2. Maintain SGLT2 inhibitor and MRA (minimal BP effect) 2
3. Consider reducing beta-blocker if BP remains low 2

If Heart Rate <60 bpm:

1. Reduce beta-blocker dose first 2
2. Maintain SGLT2 inhibitor and MRA 2
3. Consider reducing ACE inhibitor if BP remains low 2

Never discontinue guideline-directed medical therapy for asymptomatic low blood pressure—this compromises long-term survival. 2

Common Pitfalls to Avoid

Do not defer SGLT2 inhibitor initiation to outpatient setting—start during hospitalization for acute decompensated heart failure, as early initiation reduces post-discharge mortality. 1

Avoid NSAIDs completely—they interfere with ACE inhibitor efficacy, worsen renal function, and promote fluid retention. 4, 2

Do not use thiazide diuretics if eGFR <30 mL/min unless combined synergistically with loop diuretics for diuretic resistance. 2

Avoid potassium-sparing diuretics during ACE inhibitor initiation—use MRA instead, which provides mortality benefit. 4

Do not perform excessive diuresis before starting ACE inhibitors—this precipitates hypotension and renal dysfunction. 4

Never continue beta-blockers during acute decompensation—temporarily reduce or hold, then restart at low dose once stabilized. 2

Special Populations

Renal Impairment (eGFR <30 mL/min/1.73m²)

• Reduce or avoid MRA 1
• Adjust ACE inhibitor dosing (use lower starting and target doses) 1
• SGLT2 inhibitors: Do not initiate if eGFR <20-30 mL/min, but may continue if already established 1

Post-Myocardial Infarction

• Start ACE inhibitor within 24 hours if LVEF <40% or large anterior MI, even with normal EF 5, 8
• Use lisinopril 5 mg within 24 hours, then 5 mg at 48 hours, then 10 mg daily (or 2.5 mg if baseline SBP <120 mmHg) 5
• Higher incidence of persistent hypotension (9% vs 3.7%) and renal dysfunction (2.4% vs 1.1%) expected 5

Acute Decompensated Heart Failure

• Initiate SGLT2 inhibitor during hospitalization before discharge 1
• Optimize diuresis first, then start neurohormonal blockade 4
• Begin ACE inhibitor after hemodynamic stabilization 4

When to Refer for Advanced Therapy

Refer to heart failure specialist if: 2

• Persistent symptomatic hypotension preventing GDMT uptitration 2
• Refractory symptoms (NYHA Class III-IV) despite optimal medical therapy 2
• Recurrent hospitalizations for heart failure 2
• Progressive renal dysfunction limiting medication titration 2

Device Therapy Considerations

Evaluate for implantable cardioverter-defibrillator (ICD) in patients with LVEF ≤35% and ischemic heart disease after 40 days post-MI or 90 days after revascularization, once on optimal medical therapy for at least 3 months. 2

Consider cardiac resynchronization therapy (CRT) for patients in sinus rhythm with LVEF ≤35%, QRS duration ≥150 ms with left bundle branch block morphology, and persistent NYHA Class II-IV symptoms despite optimal medical therapy. 2

Follow-Up Schedule

Early follow-up within 1-2 weeks of medication changes is associated with improved outcomes: 2

• Week 1-2: Check BP, HR, potassium, creatinine after each medication change 2
• Week 4-8: Continue uptitration with lab monitoring 2
• Every 3 months: Once stable on target doses 4
• Every 6 months: Long-term maintenance 4