What is the recommended initial approach for outpatient management of heart failure with reduced ejection fraction (HFrEF)?

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

The recommended initial approach for outpatient management of HFrEF is to start 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

Core Medication Classes for HFrEF

First-Line Therapies

• 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
• 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, 3
• If ARNi is not feasible, ACE inhibitors or ARBs should be used 2

Implementation Strategy

• Evaluate blood pressure, heart rate, volume status, and renal function before initiating therapy 1
• For patients with adequate blood pressure, start SGLT2 inhibitor and MRA first, then add low-dose beta-blocker if heart rate >70 bpm, followed by ARNi (or ACEi/ARB if ARNi not feasible) 1
• For patients with low blood pressure (SBP <100 mmHg), start with SGLT2 inhibitor and MRA as they have minimal BP-lowering effects 1
• Diuretics should be used as needed for congestion but adjusted according to volume status to avoid overdiuresis which can lead to hypotension 1, 2

Evidence-Based Dosing and Monitoring

• Start medications at low doses and titrate gradually every 2-4 weeks as tolerated 1, 3
• For ARNi (sacubitril/valsartan), the recommended starting dose is 49/51 mg twice daily, with titration to 97/103 mg twice daily after 2-4 weeks as tolerated 3
• Monitor renal function, electrolytes, blood pressure, and heart rate regularly, especially when using ACEi/ARB/ARNi and MRAs 2, 1
• If beta-blockers cannot be tolerated and patient is in sinus rhythm, consider ivabradine 1, 4

Special Considerations

Patients with Low Blood Pressure

• Start with medications that have minimal BP-lowering effects (SGLT2i and MRA) 1
• Consider very low starting doses of other medications 1
• Adjust diuretics to avoid overdiuresis which can worsen hypotension 1

Hospitalized Patients

• Continue GDMT in most patients with HFrEF experiencing exacerbation requiring hospitalization, in the absence of hemodynamic instability or contraindications 2
• For hospitalized patients not previously on GDMT, initiation of these therapies is recommended in stable patients prior to hospital discharge 2
• Beta-blocker therapy should be initiated after optimization of volume status and successful discontinuation of intravenous diuretics, vasodilators, and inotropic agents 2

Common Pitfalls to Avoid

• Avoid the traditional step-by-step approach that delays benefits of comprehensive therapy 1
• Don't be overly cautious with dosing - even lower-than-target doses provide significant benefits 1, 5
• Excessive diuresis can lead to hypotension and impair tolerance of other HF medications 1
• When adjusting medications, change one drug at a time to identify the source of any adverse effects 1
• De-escalation of GDMT during hospitalization, particularly for non-cardiovascular causes, is associated with worse outcomes and should be avoided when possible 6

Follow-Up and Monitoring

• Monitor fluid intake and output, vital signs, body weight (measured at the same time each day), and clinical signs and symptoms of systemic perfusion and congestion 2
• During active titration of HF medications, regularly check serum electrolytes, urea nitrogen, and creatinine 2
• Provide comprehensive instructions regarding diet, medications, activity level, follow-up appointments, daily weight monitoring, and what to do if HF symptoms worsen 2
• Utilize post-discharge systems of care to facilitate the transition to effective outpatient care 2