Initial Management of Heart Failure with Reduced Ejection Fraction

Core Pharmacotherapy

The American Heart Association recommends initiating 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 in patients with heart failure and reduced ejection fraction (HFrEF) 1
SGLT2 inhibitors should be initiated immediately in all patients with HFrEF and eGFR >20 mL/min/1.73 m², as they have minimal blood pressure effects and provide rapid mortality benefit 2, 1, 3
ACE inhibitors are the standard starting point for all symptomatic patients (Stage C), and should be started with low doses and uptitrated to target doses proven effective in major trials 4, 5, 6, 7
Beta-blockers are recommended for all patients with stable HFrEF in NYHA class II-IV, and must be continued unless contraindicated 7, 1

For patients with baseline low blood pressure but adequate perfusion, start SGLT2 inhibitor and MRA first, as they don't lower blood pressure, and consider low-dose beta-blocker if heart rate >70 bpm 8, 3
For standard blood pressure patients, start SGLT2 inhibitor and MRA first, then add either low-dose beta-blocker or low-dose ACE inhibitor/ARNI, and uptitrate one drug at a time using small increments every 1-2 weeks 8, 3

Laboratory monitoring should include baseline complete blood count, urinalysis, fasting lipids, liver function, electrolytes, BUN, creatinine, glucose, and TSH, and after medication changes, check BP, HR, renal function, and electrolytes at 1-2 weeks after each increment 7, 4, 8, 3
Potassium-sparing diuretics should be used only if hypokalemia persists after ACE inhibitor initiation, and check potassium and creatinine after 5-7 days, and recheck every 5-7 days until stable 7

Never discontinue GDMT for asymptomatic or mildly symptomatic low blood pressure, as this compromises long-term outcomes, and avoid NSAIDs, as they interfere with ACE inhibitor efficacy and worsen renal function 2, 7
Don't use thiazides if GFR <30 mL/min, unless combined synergistically with loop diuretics, and avoid excessive diuresis before starting ACE inhibitors, as it can precipitate hypotension 7, 4

Referral criteria include persistent low blood pressure with major symptoms despite optimization attempts, inability to uptitrate GDMT due to hemodynamic intolerance, and refractory symptoms on optimal medical therapy 2, 8, 5

The European Society of Cardiology recommends the use of beta-blockers, such as bisoprolol, carvedilol, sustained-release metoprolol succinate, or nebivolol, for all patients with stable heart failure with reduced ejection fraction (HFrEF) in NYHA class II-IV 9
The European Society of Cardiology suggests that only 17-29% of patients achieve target doses of ACE inhibitors/ARBs in real-world practice, and only 13-28% achieve target doses of beta-blockers, with only 1% of eligible patients achieving target doses of all recommended drugs simultaneously 10
Cardiac Resynchronization Therapy (CRT) is recommended for patients in sinus rhythm with LVEF ≤35%, QRS duration ≥150 ms, and left bundle branch block morphology who remain symptomatic, as it improves clinical outcomes 9
Implantable Cardioverter-Defibrillator (ICD) is considered for primary prevention in patients with LVEF ≤35% and ischemic heart disease 9
Early follow-up within 1-2 weeks of medication changes is associated with improved patient outcomes, and close monitoring of blood pressure, heart rate, renal function, and electrolytes is essential 9
The use of validated tools, such as the KCCQ-12, to assess patients' health-related quality of life is recommended 9
Post-discharge interventions, including cardiac rehabilitation, have been associated with improved outcomes 9

The European Society of Cardiology recommends uptitrating one drug at a time using small increments every 1-2 weeks until target doses are achieved, with target doses proven in trials including Carvedilol 25-50 mg twice daily, bisoprolol 10 mg daily, metoprolol succinate 200 mg daily, enalapril 10-20 mg twice daily, sacubitril/valsartan 97/103 mg twice daily 11