What are the guideline medications for congestive heart failure (CHF)?

Guideline Medications for Congestive Heart Failure

All patients with heart failure and reduced ejection fraction (HFrEF, EF ≤40%) should receive quadruple therapy consisting of: (1) ARNI (sacubitril/valsartan) or ACE inhibitor, (2) beta-blocker (bisoprolol, carvedilol, or metoprolol succinate only), (3) mineralocorticoid receptor antagonist (MRA), and (4) SGLT2 inhibitor (dapagliflozin or empagliflozin). 1

Core Quadruple Therapy: The Four Pillars

1. ARNI (Preferred) or ACE Inhibitor

Start with sacubitril/valsartan (ARNI) rather than ACE inhibitors when available and tolerated—ARNI is superior. 1

ARNI Dosing:

• Start 24/26 mg twice daily if on low/medium-dose ACE inhibitor, ARB, or treatment-naïve 1
• Start 49/51 mg twice daily if previously on high-dose ACE inhibitor 1
• Target dose: 97/103 mg twice daily 1
• Use 24/26 mg twice daily starting dose for severe renal impairment, moderate hepatic impairment (Child-Pugh B), or age ≥75 years 1

ACE Inhibitor Dosing (if ARNI not available):

ACE Inhibitor	Starting Dose	Target Dose
Enalapril	2.5 mg twice daily	10-20 mg twice daily
Lisinopril	2.5-5 mg once daily	30-35 mg once daily
Ramipril	2.5 mg once daily	5 mg twice daily or 10 mg once daily
Captopril	6.25 mg three times daily	50-100 mg three times daily

2

2. Beta-Blockers (Only Three Proven to Reduce Mortality)

Only bisoprolol, carvedilol, or metoprolol succinate (CR/XL) reduce mortality—this is NOT a class effect. 3, 2, 4 Metoprolol tartrate should not be used. 3

Beta-Blocker	Starting Dose	Target Dose
Bisoprolol	1.25 mg once daily	10 mg once daily
Carvedilol	3.125 mg twice daily	25-50 mg twice daily
Metoprolol CR/XL	12.5-25 mg once daily	200 mg once daily

2, 1, 4

3. Mineralocorticoid Receptor Antagonists (MRA)

Use spironolactone or eplerenone in all patients with NYHA Class II-IV symptoms and EF ≤35% despite ACE inhibitor/ARNI and beta-blocker. 3, 1

• Spironolactone: Start 12.5-25 mg daily, target 25-50 mg daily 1
• Eplerenone: Start 25 mg daily, target 50 mg daily 1

Critical monitoring: Check potassium and creatinine at 1 and 4 weeks after starting/increasing dose 3

• If K+ >5.5 mmol/L or creatinine >221 μmol/L (2.5 mg/dL)/eGFR <30 mL/min/1.73m², halve dose 3
• If K+ >6.0 mmol/L or creatinine >310 μmol/L (3.5 mg/dL)/eGFR <20 mL/min/1.73m², stop MRA immediately 3

4. SGLT2 Inhibitors

Add dapagliflozin 10 mg daily or empagliflozin 10 mg daily regardless of diabetes status—proven mortality and hospitalization benefits. 1

Initiation Strategy: Start Fast, Titrate Together

Start ARNI/ACE inhibitor and beta-blocker simultaneously or in rapid sequence without waiting to achieve target doses before starting the next medication. 1 Titrate all medications to target doses every 2 weeks as tolerated. 1

Do not delay beta-blockers or MRAs even if patients are clinically stable—these drugs reduce sudden death risk. 3

Additional Therapies for Specific Populations

For Black Patients

Add hydralazine/isosorbide dinitrate (Class 1A recommendation) for Black patients with HFrEF who remain symptomatic despite optimal therapy. 3, 1

• Hydralazine: 25 mg three times daily, titrate to 75 mg three times daily 1
• Isosorbide dinitrate: 20 mg three times daily, titrate to 40 mg three times daily 1

For Persistent Tachycardia

Add ivabradine when resting heart rate ≥70 bpm despite maximally tolerated beta-blocker doses. 1

• Start 2.5-5 mg twice daily, titrate to heart rate 50-60 bpm, maximum 7.5 mg twice daily 1

Diuretics for Congestion Management

Furosemide and loop diuretics are for symptomatic relief of congestion only—they do NOT reduce mortality. 4

• Use only when signs/symptoms of fluid overload present: dyspnea, peripheral edema, elevated JVP, pulmonary congestion 4
• Target weight loss of 0.5-1.0 kg daily 4

Critical Pitfalls to Avoid

Never Stop Beta-Blockers Suddenly

Beta-blockers should not be stopped suddenly unless absolutely necessary—risk of rebound myocardial ischemia, infarction, and arrhythmias. 3, 4 Seek specialist advice before discontinuation. 3

Manage Worsening Congestion Correctly During Beta-Blocker Titration

If congestion worsens during beta-blocker titration, DOUBLE the diuretic dose first before reducing beta-blocker. 3, 4 Only halve beta-blocker dose if increasing diuretic does not work. 3

Don't Stop for Asymptomatic Hypotension

Do not permanently reduce doses due to asymptomatic hypotension or mild laboratory changes—temporary reduction with subsequent re-titration is appropriate. 1 Asymptomatic low blood pressure does not usually require any change in therapy. 3

Target the Evidence-Based Doses

Higher doses correlate with better outcomes—some beta-blocker is better than none if target dose cannot be achieved, but always attempt to reach target doses. 2, 4 The ATLAS trial showed greater reduction in death or hospitalization with higher ACE inhibitor doses. 2

Monitoring Requirements

Monitor blood pressure, renal function, and electrolytes within 1-2 weeks after initiation and with each dose increase. 1

For MRAs specifically: Check blood chemistry at 1 and 4 weeks after starting/increasing dose, then at 8 and 12 weeks, 6,9, and 12 months, then 4-monthly thereafter. 3

Contraindications and Cautions

Seek specialist advice for:

• Significant renal dysfunction (creatinine >221 μmol/L [>2.5 mg/dL] or eGFR <30 mL/min/1.73m²) 3, 2
• Significant hyperkalaemia (K+ >5.0 mmol/L) 3
• Severe CHF, current or recent exacerbation 2
• Heart block or heart rate <60/min 2
• Symptomatic or severe asymptomatic hypotension 2