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 inhibitors, mineralocorticoid receptor antagonists (MRAs), beta-blockers, and renin-angiotensin system inhibitors (preferably sacubitril/valsartan), along with loop diuretics for symptom relief if fluid overload is present. 1

First-Line Medication Regimen

Immediate Initiation (Start All Together)

SGLT2 Inhibitors - Start first as they have minimal blood pressure impact while providing significant mortality benefit 1:

• Dapagliflozin 10 mg daily OR empagliflozin 10 mg daily 1
• Can and should be initiated during hospitalization for acute decompensated heart failure 1
• Do not defer to outpatient setting as this exposes patients to excess risk of early post-discharge death 1
• Contraindicated if eGFR <30 mL/min/1.73m² 1

Mineralocorticoid Receptor Antagonists - Start simultaneously with SGLT2 inhibitors 1:

• Spironolactone 12.5-25 mg daily OR eplerenone 25 mg daily 1
• Indicated for NYHA Class III-IV heart failure with reduced ejection fraction to increase survival, manage edema, and reduce hospitalization 2
• Proven 30% reduction in mortality risk in landmark trials 2
• Requires eGFR >30 mL/min/1.73m² and serum potassium <5.0 mEq/L 1, 2

Beta-Blockers - Initiate after patient stabilization 1:

• Use only carvedilol, metoprolol succinate, or bisoprolol (proven mortality benefit) 3
• Start at low dose and titrate gradually 3
• Each reduces mortality by at least 20% and decreases sudden death risk 3
• Administer in morning to minimize sleep disturbances 4

Renin-Angiotensin System Inhibition 1:

• Preferred: Sacubitril/valsartan (ARNI) - provides superior reduction in heart failure hospitalization and death 5
• Alternative: ACE inhibitors (first-line if ARNI not available) 3
• Alternative: ARBs only if ACE inhibitor intolerant due to cough or angioedema 6
• Start at low dose after reducing diuretics for 24 hours 3
• Modest 5-16% mortality reduction, does not reduce sudden death 3

Diuretic Therapy for Symptom Control

Loop Diuretics - Essential when fluid overload is present 3:

• Manifest as pulmonary congestion or peripheral edema 3
• Results in rapid improvement of dyspnea and increased exercise tolerance 3
• Always combine with ACE inhibitors when possible 3
• Adjust dose based on volume status; reduce when initiating ACE inhibitors 3, 1
• No controlled trials assessing survival benefit, but necessary for symptom management 3

Titration Strategy

Simultaneous Low-Dose Initiation Approach 1, 7:

• Start multiple medications together at low doses rather than waiting to reach target dose of one before starting another 5
• Early benefits occur even with low doses of foundational therapies 7
• Gradually increase to target doses over 6-12 weeks 5
• Target doses were goals based on tolerability in trials; many patients benefited from sub-target doses 7

Titration Sequence for Blood Pressure Concerns 1:

1. Start SGLT2 inhibitor and MRA first (minimal BP effect)
2. Add beta-blocker if heart rate >70 bpm
3. Add ARNI or ACE inhibitor/ARB at low dose and titrate up
4. This sequence prioritizes medications with least BP impact while maximizing survival benefit 1

Monitoring Requirements

Initial Monitoring (1-2 weeks after initiation and each dose increment) 1, 3:

• Blood pressure and heart rate 1
• Renal function (serum creatinine) 3, 1
• Electrolytes (particularly potassium) 3, 1
• Symptoms and volume status 5

Ongoing Monitoring 5:

• At 3 months, then 6-month intervals
• Functional capacity assessment
• Daily weight monitoring by patient 4

Critical Contraindications and Precautions

Avoid or Withdraw 6:

• NSAIDs (worsen renal function and counteract HF medication benefits) 5, 3
• Most antiarrhythmic drugs (except amiodarone if needed) 8, 6
• Calcium channel blockers 6

Medication Adjustments for Renal Dysfunction 1:

• eGFR <30 mL/min/1.73m²: Reduce or avoid MRAs, adjust RAS inhibitor dosing
• If serum creatinine increases substantially, stop ACE inhibitor 3

Hyperkalemia Management 1:

• If K+ >5.0 mEq/L: Reduce MRA dose first
• Avoid potassium-sparing diuretics during ACE inhibitor initiation 3

Common Pitfalls to Avoid

Do not delay initiation of all four medication classes - The emphasis has shifted from sequential titration to target doses toward rapid initiation of all foundational therapies 7

Do not reduce GDMT for asymptomatic or mildly symptomatic low blood pressure - This compromises long-term outcomes 4

Do not withhold medications based on "stable" symptoms - SGLT2 inhibitors, beta-blockers, and MRAs reduce sudden death risk and cannot be reasonably delayed 3

Do not defer SGLT2 inhibitor initiation to outpatient setting - In-hospital initiation is consistent with regulatory labels and reduces early post-discharge mortality 1

Underutilization and inadequate dose titration - These remain the most common management errors 5

Special Populations

Low Blood Pressure Management 4:

• If symptomatic hypotension with heart rate >70 bpm: Reduce ACEi/ARB/ARNI first
• If symptomatic hypotension with heart rate <60 bpm: Reduce beta-blocker first
• Maintain SGLT2 inhibitors and MRAs (least BP effect) 4

Non-Ischemic vs Ischemic Etiology 9:

• Non-ischemic etiologies (especially tachycardiomyopathy and valvular) show higher rates of LVEF improvement (63% achieve improvement within 3-4 months) 9
• Ischemic cardiomyopathy less likely to improve but still requires full GDMT 9