Guideline-Directed Medical Therapy (GDMT) for Heart Failure
GDMT for heart failure with reduced ejection fraction (HFrEF, LVEF ≤40%) consists of four foundational medication classes that should be initiated and optimized to reduce mortality and hospitalizations: SGLT2 inhibitors, ARNi/ACEi/ARB, beta-blockers, and mineralocorticoid receptor antagonists (MRAs). 1
Core Medication Classes for HFrEF (LVEF ≤40%)
First-Line Quadruple Therapy
SGLT2 Inhibitors 1
- Dapagliflozin 10 mg daily OR empagliflozin 10 mg daily 1
- Start early in treatment course, minimal blood pressure effects 1
- Reduces heart failure hospitalizations and cardiovascular mortality 2, 1
- Preferred: Sacubitril/valsartan (ARNi) starting 24/26-49/51 mg twice daily, titrate to target 97/103 mg twice daily 1
- Alternative: ACE inhibitors (lisinopril, enalapril) if ARNi not tolerated 2
- Alternative: ARBs (valsartan) if ACEi causes intolerable cough or angioedema 2, 4
- Reduces mortality by 5-16% for ACEi/ARBs, at least 20% for ARNi 3
- Evidence-based agents only: carvedilol, metoprolol succinate, or bisoprolol 2, 1
- Target doses: Carvedilol 25-50 mg twice daily, metoprolol succinate 200 mg daily, bisoprolol 10 mg daily 1
- Start at low doses and titrate upward 2
- Reduces mortality by at least 20% 3
Mineralocorticoid Receptor Antagonists (MRAs) 1, 3
- Spironolactone 12.5-25 mg daily OR eplerenone 25 mg daily 1
- Titrate to target: spironolactone 25-50 mg daily, eplerenone 50 mg daily 1
- Indicated for LVEF ≤35% with NYHA class II-IV symptoms 2, 1
- Reduces mortality by at least 20% 3
- Monitor potassium and renal function closely 2
Combined Therapy Impact
- Quadruple therapy reduces mortality risk by approximately 73% over 2 years compared to no treatment 3
- Transitioning from dual therapy (ACEi + beta-blocker) to quadruple therapy extends life expectancy by approximately 6 years 3
Additional Therapies for Selected Patients
Diuretics 2
- Loop diuretics (furosemide, bumetanide, torsemide) for volume overload and symptom relief 2
- Not mortality-reducing but essential for congestion management 2
- Titrate to achieve euvolemia 2
Ivabradine 1
- Starting dose 2.5-5 mg twice daily 1
- For patients in sinus rhythm with heart rate ≥70 bpm despite maximally tolerated beta-blocker 1
Hydralazine/Isosorbide Dinitrate 1, 4
- Additional benefit in self-identified African American patients with NYHA class III-IV symptoms 1
- Alternative for patients intolerant to ACEi/ARB/ARNi due to hypotension or renal dysfunction 4
Digoxin 4
Device Therapies
Implantable Cardioverter-Defibrillator (ICD) 2, 1
- LVEF ≤35% (≤30% if >40 days post-MI) despite ≥3 months optimal medical therapy 2, 1
- NYHA class I symptoms with expected survival >1 year 2
Cardiac Resynchronization Therapy (CRT) 2, 1
Heart Failure with Preserved Ejection Fraction (HFpEF, LVEF ≥50%)
- SGLT2 inhibitors (dapagliflozin or empagliflozin): strongest recommendation (Class 2a) for reducing HF hospitalizations 3
- Blood pressure control: cornerstone of management (Class I recommendation) 2, 3
- Diuretics: for volume overload symptom relief 2
- MRAs: weaker recommendation (Class 2b) for reducing hospitalizations 3
- Atrial fibrillation management: for symptom control 2, 3
Critical Implementation Principles
Titration Strategy 2, 3
- Initiate all four medication classes at low doses simultaneously or in rapid sequence 3
- Uptitrate every 1-2 weeks until target doses achieved 3
- Alternate adjustments between medication classes (especially ACEi/ARB/ARNi and beta-blockers) 2
- Monitor vital signs, renal function, and electrolytes 1-2 weeks after each dose increment 2, 3
Managing Common Barriers 2, 3
Hypotension 2
- Monitor postural changes, especially in patients with orthostatic symptoms or systolic BP 80-100 mmHg 2
- Patients with low BP but adequate perfusion can tolerate therapy with small incremental increases 3
- Reassure patients that transient fatigue/weakness often resolves within days 2
- Modest creatinine increases (up to 30% above baseline) are acceptable and should not prompt discontinuation 3
- Discuss tolerable creatinine levels with nephrologist if necessary 2
- Monitor potassium closely when combining MRAs with ARNi 1
- Avoid MRAs if potassium >5.0 mmol/L or eGFR <30 mL/min/1.73m² 1
Special Populations
HF with Improved EF (HFimpEF) 1, 3
- Patients with previous HFrEF whose LVEF improves to >40% should continue their HFrEF treatment regimen 1, 3
- Discontinuation may lead to clinical deterioration 3
Elderly and Chronic Kidney Disease 2
- Require more frequent monitoring and gradual dose changes 2
- These vulnerable patients accrue considerable benefits from GDMT 2
Prevention Strategies (Stage A: At Risk for HF)
Primary Prevention 2
- Control hypertension according to guidelines 2
- SGLT2 inhibitors in type 2 diabetes with established CVD or high CV risk to prevent HF hospitalizations 2
- Healthy lifestyle: regular physical activity, normal weight, healthy diet, smoking avoidance 2
- Statins in patients with recent/remote MI or acute coronary syndrome 2
Stage B (Pre-HF: Asymptomatic LVEF ≤40%)
Recommended Therapies 2
- ACE inhibitors to prevent symptomatic HF and reduce mortality 2
- ARBs if ACEi intolerant (post-MI with LVEF ≤40%) 2
- Evidence-based beta-blockers 2
- Statins (post-MI patients) 2
Medications to Avoid in HFrEF
Contraindicated or Harmful 4
- Calcium channel blockers (except amlodipine) 4
- Oral or intravenous inotropes for routine use 2, 4
- NSAIDs (worsen fluid retention) 4
- Thiazolidinediones (rosiglitazone, pioglitazone) 4
Hospital Discharge and Transitions of Care
Before Discharge 2
- Initiate GDMT if not previously established and not contraindicated 2
- Optimize chronic oral HF therapy 2
- Assess volume status and adjust therapy 2
- Monitor renal function and electrolytes 2
- Continue or initiate beta-blockers at low dose after optimization of volume status 2
- Continue HFrEF GDMT except in hemodynamic instability 2
Post-Discharge Follow-up 2