Initial Outpatient Management of Heart Failure with Reduced Ejection Fraction (HFrEF)

Core Medication Classes for HFrEF

The American Heart Association recommends starting all four core medication classes simultaneously at low doses with gradual titration, beginning with SGLT2 inhibitors and mineralocorticoid receptor antagonists (MRAs) due to their minimal effect on blood pressure 1
SGLT2 inhibitors should be initiated early as they provide rapid benefits with minimal blood pressure effects and remain effective even with moderate kidney dysfunction (eGFR ≥30 ml/min/1.73 m² for empagliflozin, ≥20 ml/min/1.73 m² for dapagliflozin) 1
Mineralocorticoid Receptor Antagonists (MRAs) are indicated for patients with LVEF ≤35% and NYHA class II-IV symptoms and should be started early due to minimal blood pressure effects 1, 2
The American College of Cardiology recommends that beta-blockers should be initiated at low doses if heart rate >70 bpm, with selective β₁ receptor blockers potentially preferred due to lesser blood pressure-lowering effects 1
ARNi (sacubitril/valsartan) is recommended for NYHA class II-III symptoms, starting with low dose (24/26 mg to 49/51 mg twice daily) 1, 2
If ARNi is not feasible, ACE inhibitors or ARBs should be used, as recommended by the European Society of Cardiology 3, 2

Medications should be started at low doses and titrated gradually every 2-4 weeks as tolerated, according to the American Heart Association 1
Monitor renal function, electrolytes, blood pressure, and heart rate regularly, especially when using ACEi/ARB/ARNi and MRAs, as recommended by the European Heart Journal 3, 1

For patients with low blood pressure, start with medications that have minimal BP-lowering effects (SGLT2i and MRA), as recommended by the American College of Cardiology 1
The American Heart Association recommends that hospitalized patients with HFrEF should continue GDMT in most patients experiencing exacerbation requiring hospitalization, in the absence of hemodynamic instability or contraindications 4

The American College of Cardiology recommends monitoring fluid intake and output, vital signs, body weight, and clinical signs and symptoms of systemic perfusion and congestion 5
During active titration of HF medications, regularly check serum electrolytes, urea nitrogen, and creatinine, as recommended by the Journal of the American College of Cardiology 5
Provide comprehensive instructions regarding diet, medications, activity level, follow-up appointments, daily weight monitoring, and what to do if HF symptoms worsen, according to the American Heart Association 4