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 patients with newly diagnosed HFrEF: SGLT2 inhibitors, mineralocorticoid receptor antagonists (MRAs), beta-blockers, and renin-angiotensin system (RAS) inhibitors, with gradual titration over 6-12 weeks rather than waiting to reach target doses sequentially. 1

Core Medication Regimen

First-Line Therapy (Start Simultaneously)

SGLT2 Inhibitors - Initiate immediately as they have minimal blood pressure effects while providing significant mortality benefits 1:

• Dapagliflozin 10 mg daily OR empagliflozin 10 mg daily 1
• Can be started during hospitalization for acute decompensated heart failure 1
• Continue if eGFR ≥30 mL/min/1.73m²; do not initiate if eGFR <30 1

Mineralocorticoid Receptor Antagonists - Start concurrently with SGLT2 inhibitors 1:

• Spironolactone 12.5-25 mg daily OR eplerenone 25 mg daily 1
• FDA-approved for NYHA Class III-IV heart failure with reduced ejection fraction to increase survival, manage edema, and reduce hospitalization 2
• Requires eGFR >30 mL/min/1.73m² and serum potassium <5.0 mEq/L 2
• In the landmark RALES trial, spironolactone reduced mortality risk by 30% (p<0.001) in patients with LVEF ≤35% 2

Beta-Blockers - Evidence-based agents only 3:

• Carvedilol, metoprolol succinate, OR bisoprolol 3
• Start at low doses after initiating SGLT2 inhibitor and MRA, particularly if heart rate >70 bpm 1
• Each reduces mortality risk by at least 20% and decreases sudden death 3

RAS Inhibition - Choose one agent 3, 1:

• Preferred: Sacubitril/valsartan (ARNI) at low dose for superior outcomes 4
• Alternative: ACE inhibitor (e.g., lisinopril starting 2.5-5 mg daily) 3, 5
• If ACE-intolerant: ARB for cough or angioedema 3
• ACE inhibitors provide modest 5-16% mortality reduction but are foundational therapy 3

Diuretic Therapy for Symptom Control

Loop diuretics are essential when fluid retention is present (pulmonary congestion or peripheral edema) 3:

• Provide rapid improvement in dyspnea and exercise tolerance 3
• Adjust dose based on volume status 1
• Reduce diuretic dose when initiating ACE inhibitors to prevent excessive hypotension 3
• Always combine with ACE inhibitors when possible 3

Titration Strategy

Use a rapid initiation approach rather than sequential dose escalation 1, 6:

• Start multiple medications at low doses simultaneously 4
• Titrate gradually to target doses over 6-12 weeks 4
• Benefits occur even with low doses; target doses were goals based on tolerability in trials, not minimum effective doses 6
• Average doses in landmark trials were often below target, yet demonstrated significant benefits 6

Specific Titration Sequence 1:

1. Start SGLT2 inhibitor and MRA together (minimal BP effect)
2. Add beta-blocker if heart rate >70 bpm
3. Add ARNI or ACE inhibitor/ARB at low dose
4. Titrate each medication upward as tolerated

Monitoring Parameters

Check renal function and electrolytes 1-2 weeks after initiation and each dose increment 3, 1:

• Blood pressure and heart rate at each visit 1
• Renal function and potassium at 1-2 weeks, then at 3 months, then every 6 months 4
• Daily weight monitoring by patient 7

Special Populations and Dose Adjustments

Patients with eGFR <30 mL/min/1.73m² 1:

• Reduce or avoid MRAs
• Adjust RAS inhibitor dosing
• Do not initiate SGLT2 inhibitors (may continue if already established)

Patients with hyperkalemia (K+ >5.0 mEq/L) 1:

• Reduce MRA dose first
• Exclude baseline potassium >5.0 mEq/L before starting spironolactone 2

Patients with symptomatic hypotension 7, 4:

• If heart rate >70 bpm: reduce ACE inhibitor/ARB/ARNI first 7
• If heart rate <60 bpm: reduce beta-blocker first 7
• Maintain SGLT2 inhibitors and MRAs as they have least BP effect 7

Critical Pitfalls to Avoid

Do not defer SGLT2 inhibitor initiation to outpatient setting - in-hospital initiation prevents excess risk of early post-discharge worsening and death 1

Do not reduce guideline-directed medical therapy for asymptomatic or mildly symptomatic low blood pressure - this compromises long-term outcomes 7

Avoid NSAIDs - they worsen renal function and counteract beneficial effects of heart failure medications 3, 4

Do not use non-evidence-based beta-blockers - only carvedilol, metoprolol succinate, and bisoprolol have proven mortality benefits 3

Do not delay starting multiple medications sequentially - simultaneous low-dose initiation is superior to sequential target-dose achievement 4, 6