Initial Management Approach for Heart Failure with Reduced Ejection Fraction (HFrEF)

Core Medication Classes for HFrEF

The European Society of Cardiology recommends starting all four core medication classes simultaneously at low doses and titrating gradually, with SGLT2 inhibitors and mineralocorticoid receptor antagonists (MRAs) initiated first due to their minimal effect on blood pressure 1, 2
SGLT2 inhibitors should be started early as they have minimal effect on blood pressure but provide rapid benefits, and are effective even with moderate kidney dysfunction (eGFR ≥30 ml/min/1.73 m² for empagliflozin, ≥20 ml/min/1.73 m² for dapagliflozin) 1, 3
Mineralocorticoid Receptor Antagonists (MRAs) should be started early as they have minimal effect on blood pressure, and are indicated especially for patients with LVEF ≤35% and NYHA class II-IV symptoms 1, 4, 5
Beta-blockers should be considered starting at low dose if heart rate >70 bpm, and selective β₁ receptor blockers may be preferred due to lesser BP-lowering effect 1
The American Heart Association recommends ARNi (sacubitril/valsartan) for NYHA class II-III symptoms, starting with low dose (25-50 mg twice daily) of sacubitril/valsartan 4, 5

Evaluate blood pressure, heart rate, volume status, and renal function, and adjust diuretics according to volume status to avoid overdiuresis which can lead to hypotension 1, 3
For patients with adequate blood pressure, start SGLT2 inhibitor and MRA first, then add low-dose beta-blocker if heart rate >70 bpm, and add low-dose ARNi (or ACEi/ARB if ARNi not feasible) 1, 3, 4
For patients with low blood pressure (SBP <100 mmHg), start with SGLT2 inhibitor and MRA as they have minimal BP-lowering effects, and consider very low starting doses of other medications 1, 3

Diuretics should be used as needed for congestion but adjusted according to volume status to avoid overdiuresis which can lead to hypotension 1
For patients with low baseline BP, consider starting with medications that have minimal BP-lowering effects (SGLT2i and MRA) 1, 3
Renal function should be monitored closely, especially when using ACEi/ARB/ARNi and MRAs 3
If beta-blockers cannot be tolerated and patient is in sinus rhythm, consider ivabradine 1

Avoid the traditional step-by-step approach that delays benefits of comprehensive therapy, and don't be overly cautious with dosing - even lower-than-target doses provide significant benefits 3
Excessive diuresis can lead to hypotension and impair tolerance of other HF medications, and medications should be adjusted based on clinical response, with one drug at a time to identify the source of any adverse effects 1, 3

The American College of Cardiology recommends the use of beta-blockers (carvedilol, metoprolol succinate, or bisoprolol) and mineralocorticoid receptor antagonists (MRAs) (spironolactone or eplerenone) as part of guideline-directed medical therapy (GDMT) for HFrEF 6
The American College of Cardiology suggests that in patients with HFrEF requiring hospitalization, GDMT should be initiated during hospitalization after clinical stability is achieved, and preexisting GDMT should be continued and optimized during hospitalization, unless contraindicated 7

According to the American College of Cardiology, even in patients experiencing mild decrease of renal function or asymptomatic reduction of blood pressure during hospitalization, diuresis and other GDMT should not routinely be discontinued 7
The American College of Cardiology recommends that continuation or initiation of GDMT in hospitalized patients is associated with lower risk of post-discharge death and readmission 7