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

Initial Management of Heart Failure with Reduced Ejection Fraction

For patients with heart failure and reduced ejection fraction (HFrEF), initiate four foundational medication classes simultaneously: SGLT2 inhibitors, ACE inhibitors (or ARNI/ARB), beta-blockers, and mineralocorticoid receptor antagonists (MRAs), along with diuretics for fluid retention. 1

Core Pharmacotherapy (Four Pillars of GDMT)

First-Line Medications - Start All Four Classes

1. SGLT2 Inhibitors

• Initiate immediately in all patients with HFrEF and eGFR >20 mL/min/1.73 m² 1
• These have minimal blood pressure effects and provide rapid mortality benefit 1
• Should be prioritized as they don't lower blood pressure 1

2. Renin-Angiotensin System Inhibition

• ACE inhibitors are the standard starting point for all symptomatic patients (Stage C) 1
• Start with low doses and uptitrate to target doses proven effective in major trials 1
• ARNI (sacubitril/valsartan) is superior to ACE inhibitors for reducing mortality and should be considered as replacement therapy 1, 2
• ARBs are alternatives only if ACE inhibitors cause cough or angioedema 1, 3

3. Beta-Blockers

• Recommended for all patients with stable HFrEF in NYHA class II-IV 1
• Must be continued unless contraindicated 1
• Selective β₁ receptor blockers (metoprolol, bisoprolol) preferred over carvedilol in patients with low blood pressure 1
• For post-MI patients, continue for at least 3 years 1

4. Mineralocorticoid Receptor Antagonists (MRAs)

• Add spironolactone in NYHA class III-IV to improve survival 1
• Initiate if eGFR >25-30 mL/min/1.73 m² and potassium <5.0 mEq/L 1
• Monitor potassium and creatinine after 5-7 days, then regularly 1

Diuretics for Fluid Management

Loop Diuretics

• Always use in addition to ACE inhibitors for patients with fluid retention 1
• Start with loop diuretics or thiazides initially 1
• If GFR <30 mL/min, avoid thiazides except synergistically with loop diuretics 1
• For insufficient response: increase dose, combine loop diuretics with thiazides, or administer twice daily 1
• In severe chronic heart failure, add metolazone with frequent monitoring 1

Medication Initiation Strategy

Standard Blood Pressure Patients

Sequential approach:

1. Start SGLT2 inhibitor and MRA first (minimal BP effect) 1
2. Then add either low-dose beta-blocker (if HR >70 bpm) OR low-dose ACE inhibitor/ARNI 1
3. Uptitrate one drug at a time using small increments every 1-2 weeks 1
4. Close monitoring with BP, HR, renal function, and electrolytes at 1-2 weeks after each dose increment 1

Low Blood Pressure Patients (Special Considerations)

For patients with baseline low BP but adequate perfusion:

• Start SGLT2 inhibitor and MRA first as they don't lower BP 1
• Consider low-dose beta-blocker if HR >70 bpm 1
• Use very low-dose sacubitril/valsartan (25 mg twice daily) or low-dose ACE inhibitor 1
• Selective β₁ blockers (metoprolol, bisoprolol) preferred over carvedilol 1
• If beta-blockers not tolerated and patient in sinus rhythm, use ivabradine 1, 4

ACE Inhibitor Initiation Protocol

Critical safety steps: 1

1. Review and reduce diuretics 24 hours before starting
2. Avoid excessive diuresis before treatment
3. Start with low dose, preferably in evening when supine
4. Build up to maintenance doses from major trials
5. Stop if renal function deteriorates substantially
6. Avoid potassium-sparing diuretics during initiation
7. Avoid NSAIDs
8. Check BP, renal function, electrolytes at 1-2 weeks after each increment, at 3 months, then every 6 months

Additional Medications Based on Clinical Context

Cardiac Glycosides (Digoxin)

Indications: 1

• Atrial fibrillation with any degree of symptomatic HF: to slow ventricular rate (0.25-0.375 mg daily if normal creatinine)
• Sinus rhythm with persistent symptoms: despite ACE inhibitor and diuretic treatment
• Combination with beta-blocker superior to either alone

Contraindications: bradycardia, 2nd/3rd degree AV block, sick sinus syndrome, hypokalaemia, hypercalcaemia 1

Ivabradine

Specific indication: 4

• Reduce hospitalization risk in stable symptomatic chronic HF with LVEF ≤35%
• Sinus rhythm with resting HR ≥70 bpm
• On maximally tolerated beta-blockers OR contraindication to beta-blockers
• Starting dose: 2.5 mg (vulnerable adults) or 5 mg twice daily with food
• Adjust after 2 weeks based on heart rate; maximum 7.5 mg twice daily

Alternative use: 1

• When beta-blockers not tolerated hemodynamically in sinus rhythm
• Can facilitate beta-blocker titration when used together

Critical Monitoring Parameters

Laboratory Monitoring Schedule 1

• Baseline: Complete blood count, urinalysis, fasting lipids, liver function, electrolytes (including calcium and magnesium), BUN, creatinine, glucose, TSH
• After medication changes: 1-2 weeks for BP, HR, renal function, electrolytes 1
• Routine follow-up: 3 months, then every 6 months 1

Potassium-Sparing Diuretics Monitoring 1

• Use only if hypokalaemia persists after ACE inhibitor initiation
• Check potassium and creatinine after 5-7 days
• Recheck every 5-7 days until stable
• Serum creatinine should be ≤2.5 mg/dL (men) or ≤2.0 mg/dL (women)
• Serum potassium should be <5.0 mEq/L

Common Pitfalls to Avoid

Critical errors: 1

• Never discontinue GDMT for asymptomatic or mildly symptomatic low BP - this compromises long-term outcomes
• Avoid NSAIDs - they interfere with ACE inhibitor efficacy and worsen renal function
• Don't use thiazides if GFR <30 mL/min unless combined synergistically with loop diuretics
• Avoid excessive diuresis before starting ACE inhibitors - can precipitate hypotension
• Don't start multiple medications simultaneously in low BP patients - uptitrate one drug at a time
• Never use potassium-sparing diuretics during ACE inhibitor initiation - risk of hyperkalemia

Medications to Avoid or Withdraw

Contraindicated or harmful: 3

• NSAIDs
• Most antiarrhythmic drugs
• Calcium channel blockers (except for specific indications)
• Excessive alcohol intake 1

When to Refer for Advanced Therapy

Referral criteria: 1

• Persistent low BP with major symptoms despite optimization attempts
• Inability to uptitrate GDMT due to hemodynamic intolerance
• Refractory symptoms on optimal medical therapy
• Consider device therapy (ICD, CRT) evaluation 3