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 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 as your initial two drugs because they 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) or eplerenone 25 mg daily for patients with eGFR >30 mL/min/1.73m² and potassium <5.0 mEq/L 1, 3
• Loop diuretic: Dose adjusted to achieve euvolemia and relieve dyspnea/edema; reduce dose when initiating ACE inhibitors to prevent excessive hypotension 4, 2

Add Within Days to Weeks

After establishing SGLT2 inhibitor and MRA, add either beta-blocker or ACE inhibitor based on heart rate:

• If heart rate >70 bpm: Add low-dose beta-blocker (bisoprolol, carvedilol, or metoprolol succinate) 1, 2
• If heart rate <70 bpm: Add low-dose ACE inhibitor (lisinopril 2.5-5 mg, enalapril, or ramipril) 4, 5
• Then add the remaining drug (ACE inhibitor if you started beta-blocker first, or vice versa) within 1-2 weeks 2

ACE Inhibitor Initiation Protocol

Follow this specific sequence when starting ACE inhibitors to minimize hypotension risk: 4

1. Review and reduce diuretic dose 24 hours before ACE inhibitor initiation if patient is not volume overloaded 4
2. Avoid excessive diuresis before treatment; withhold diuretics for 24 hours if possible 4
3. Start in the evening when supine to minimize blood pressure effects, or if starting in morning, supervise for several hours with blood pressure monitoring 4
4. Begin with low dose: Lisinopril 2.5-5 mg daily, especially if systolic BP <120 mmHg 5
5. Avoid potassium-sparing diuretics during initiation 4
6. Avoid NSAIDs as they interfere with ACE inhibitor efficacy and worsen renal function 4, 2

Dose Titration Strategy

Uptitrate one drug at a time using small increments every 1-2 weeks, prioritizing getting all four drugs on board over reaching target doses. 1, 2, 6

• Target doses proven in trials: ACE inhibitors (lisinopril 20-35 mg daily), beta-blockers (carvedilol 25 mg twice daily, metoprolol succinate 200 mg daily, bisoprolol 10 mg daily), MRA (spironolactone 25-50 mg daily), SGLT2 inhibitors (already at target dose) 3, 5, 6
• However, benefits occur even at low doses—the average doses in major trials were often below target, and early mortality benefits are seen with sub-target dosing 6
• Only 1% of patients achieve target doses of all drugs simultaneously in real-world practice, so focus on initiating all four classes rather than maximizing individual doses 2

Critical Monitoring Parameters

Check these labs at baseline and 1-2 weeks after each medication change: 4, 2

• Baseline: Complete blood count, urinalysis, fasting lipids, liver function, electrolytes, BUN, creatinine, glucose, TSH 2
• After each dose change: Blood pressure, heart rate, potassium, creatinine 4, 2
• For MRA specifically: Check potassium and creatinine after 5-7 days, then recheck every 5-7 days until stable 2
• Stop ACE inhibitor if: Creatinine increases >30% or potassium >5.5 mEq/L 4

Managing Low Blood Pressure During Titration

Never discontinue guideline-directed medical therapy for asymptomatic or mildly symptomatic low blood pressure, as this compromises long-term survival. 2

If symptomatic hypotension occurs with adequate perfusion: 1, 2

• Maintain SGLT2 inhibitor and MRA (they have minimal BP effects) 1
• If heart rate >70 bpm: Reduce ACE inhibitor/ARB/ARNI dose first 1
• If heart rate <60 bpm: Reduce beta-blocker dose first 1
• Reduce diuretic dose if patient is euvolemic 2

Special Populations

For patients with eGFR <30 mL/min/1.73m²: 1

• Reduce or avoid MRA (contraindicated if K+ >5.0 mEq/L) 1
• Adjust ACE inhibitor dosing downward 1
• Continue SGLT2 inhibitor if already established, though some guidelines suggest not initiating below eGFR 20-30 1
• Avoid thiazides unless combined synergistically with loop diuretics 2

For patients with baseline creatinine >2.5 mg/dL or potassium >5.0 mEq/L: 3

• These patients were excluded from major MRA trials 3
• Exercise extreme caution with MRA and ACE inhibitors 3

In-Hospital Initiation

Initiate SGLT2 inhibitors during hospitalization for acute decompensated heart failure—do not defer to outpatient setting, as this exposes patients to excess risk of early post-discharge death. 1

Start all four medication classes before discharge when hemodynamically stable, as early follow-up within 1-2 weeks of medication changes improves outcomes. 2

Common Pitfalls to Avoid

• Don't wait to achieve target dose of one drug before starting the next—initiate all four classes quickly, then uptitrate gradually 1, 2, 6
• Don't discontinue beta-blockers unless absolutely contraindicated; they must be continued in all stable HFrEF patients NYHA class II-IV 2
• Don't use potassium-sparing diuretics routinely—only if hypokalemia persists after ACE inhibitor initiation 2
• Don't combine ACE inhibitor with ARB—use ARNI (sacubitril/valsartan) instead if considering dual RAAS blockade 1
• Don't prescribe NSAIDs—they antagonize ACE inhibitor effects and worsen renal function 4, 2

When to Refer for Advanced Therapy

Refer to heart failure specialist if: 2

• Persistent low blood pressure with major symptoms despite optimization attempts 2
• Inability to uptitrate guideline-directed medical therapy due to hemodynamic intolerance 2
• Refractory symptoms (NYHA class III-IV) on optimal medical therapy 2
• Consider ICD for primary prevention if LVEF ≤35% with ischemic heart disease after 40 days post-MI 2
• Consider CRT if LVEF ≤35%, QRS ≥150 ms with LBBB morphology, and persistent symptoms 2