What are the latest treatment guidelines for heart failure, particularly for patients with reduced ejection fraction?

Latest Treatment Guidelines for Heart Failure with Reduced Ejection Fraction

Core Pharmacotherapy: Four-Pillar Approach

All patients with HFrEF should be initiated on four foundational medication classes simultaneously: SGLT2 inhibitors, ACE inhibitors (or ARNI/ARB), beta-blockers, and mineralocorticoid receptor antagonists (MRAs), along with loop diuretics for fluid retention. 1

First-Line Medications

SGLT2 Inhibitors (Start Immediately)

• Initiate SGLT2 inhibitors (dapagliflozin 10 mg daily or empagliflozin 10 mg daily) as the first medication in all patients with HFrEF and eGFR >20 mL/min/1.73 m². 1, 2
• These agents provide rapid mortality benefit with minimal blood pressure effects, making them ideal for early initiation. 1
• SGLT2 inhibitors should be started during hospitalization for acute decompensated heart failure—deferring to outpatient setting exposes patients to excess risk of early post-discharge death. 2
• Benefits are incremental and consistent regardless of background medical therapy, including in non-diabetic patients. 2

Mineralocorticoid Receptor Antagonists

• Start spironolactone 12.5-25 mg daily or eplerenone 25 mg daily concurrently with SGLT2 inhibitors in patients with eGFR >30 mL/min/1.73 m². 2
• MRAs are indicated for NYHA Class III-IV heart failure with reduced ejection fraction to increase survival, manage edema, and reduce hospitalization. 3
• These agents have minimal blood pressure effects and should be maintained when possible. 4

ACE Inhibitors/ARBs/ARNI

• ACE inhibitors are the standard starting point for all symptomatic patients (Stage C). 1
• Start with low doses and uptitrate to target doses proven effective in major trials (e.g., enalapril 10 mg twice daily, lisinopril 20-40 mg daily). 1
• Sacubitril/valsartan (ARNI) can replace ACE inhibitors or ARBs in patients with persistent symptoms despite optimal medical therapy. 5, 6

Beta-Blockers

• Use bisoprolol, carvedilol, sustained-release metoprolol succinate, or nebivolol. 7
• Beta-blockers are recommended for all patients with stable HFrEF in NYHA class II-IV. 1
• Administer in the morning rather than at night to minimize sleep disturbances. 4

Medication Initiation Strategy

For Patients with Normal Blood Pressure:

• Start SGLT2 inhibitor and MRA first. 1
• Add either low-dose beta-blocker (if heart rate >70 bpm) or low-dose ACE inhibitor/ARNI. 1
• Uptitrate one drug at a time using small increments every 1-2 weeks. 1

For Patients with Baseline Low Blood Pressure but Adequate Perfusion:

• Start SGLT2 inhibitor and MRA first (they don't lower blood pressure). 1
• Consider low-dose beta-blocker if heart rate >70 bpm. 1
• SGLT2 inhibitors and MRAs have the least effect on BP and should be maintained when possible. 4

Diuretic Management

Loop Diuretics

• Administer for symptom relief in patients with fluid retention (evidence of fluid overload). 7, 2
• Adjust diuretic dose based on volume status and reduce when initiating ACE inhibitors. 2
• Avoid excessive diuresis before starting ACE inhibitors, as it can precipitate hypotension. 1
• Loop diuretics show better effect profile compared to thiazide diuretics. 5
• Don't use thiazides if GFR <30 mL/min unless combined synergistically with loop diuretics. 1

Monitoring and Dose Titration

Laboratory Monitoring:

• Baseline: complete blood count, urinalysis, fasting lipids, liver function, electrolytes, BUN, creatinine, glucose, and TSH. 1
• After medication changes: check BP, heart rate, renal function, and electrolytes at 1-2 weeks after each increment. 1, 2
• For potassium-sparing diuretics: check potassium and creatinine after 5-7 days, recheck every 5-7 days until stable. 1

Target Doses:

• Only 17-29% of patients achieve target doses of ACE inhibitors/ARBs in real-world practice. 7
• Only 13-28% achieve target doses of beta-blockers. 7
• Target doses of all recommended drugs are simultaneously achieved in only 1% of eligible patients. 7
• Despite these statistics, aggressive uptitration to target doses proven in clinical trials remains the goal. 1

Additional Therapies

Ivabradine:

• Indicated to reduce hospitalization risk in patients with stable, symptomatic chronic HF with LVEF ≤35%, sinus rhythm with resting heart rate ≥70 bpm, who are on maximally tolerated beta-blockers or have contraindication to beta-blocker use. 8
• Starting dose is 2.5 mg (vulnerable adults) or 5 mg twice daily with food; maximum dose 7.5 mg twice daily. 8

Iron Supplementation:

• Achieving optimal iron status is important (the threshold to start substitution is significantly higher than in patients without heart failure). 5

Device Therapy

Cardiac Resynchronization Therapy (CRT):

• Clinical outcomes improve with CRT for patients in sinus rhythm with LVEF ≤35%, QRS duration ≥150 ms, and left bundle branch block morphology who remain symptomatic. 7

Implantable Cardioverter-Defibrillator (ICD):

• Consider for primary prevention in patients with LVEF ≤35% and ischemic heart disease. 7

Special Populations and Adjustments

Renal Impairment:

• If eGFR <30 mL/min/1.73 m², reduce or avoid MRAs and adjust RAS inhibitor dosing. 2
• Do not start SGLT2 inhibitors if eGFR <30 mL/min/1.73 m² (though some agents may be continued if already established). 2

Hyperkalemia:

• For potassium >5.0 mEq/L, reduce MRA dose first. 2

Symptomatic Hypotension:

• Never discontinue guideline-directed medical therapy for asymptomatic or mildly symptomatic low blood pressure—this compromises long-term outcomes. 4, 1
• If symptomatic low BP with heart rate >70 bpm: consider reducing ACE inhibitor/ARB/ARNI first. 4
• If symptomatic low BP with heart rate <60 bpm: consider reducing beta-blockers first. 4
• Space out medications to reduce synergistic hypotensive effects. 4

Critical Pitfalls to Avoid

• Never reduce or discontinue GDMT for asymptomatic or mildly symptomatic low blood pressure. 4, 1
• Avoid NSAIDs—they interfere with ACE inhibitor efficacy and worsen renal function. 1
• Don't defer SGLT2 inhibitor initiation to outpatient setting. 2
• Avoid excessive diuresis before starting ACE inhibitors. 1
• Previously advocated therapeutic anticoagulation in patients with severely reduced LVEF is no longer recommended. 5

Follow-Up and Quality Indicators

Early Post-Discharge Care:

• Early follow-up within 1-2 weeks of medication changes is associated with improved patient outcomes. 7
• Close monitoring of blood pressure, heart rate, renal function, and electrolytes is essential. 4

Health-Related Quality of Life:

• Use validated tools (e.g., KCCQ-12) to assess patients' health-related quality of life. 7

Cardiac Rehabilitation:

• Post-discharge interventions including cardiac rehabilitation have been associated with improved outcomes. 7

When to Refer for Advanced Therapy

Referral Criteria:

• Persistent low blood pressure with major symptoms despite optimization attempts. 1
• Inability to uptitrate GDMT due to hemodynamic intolerance. 1
• Refractory symptoms on optimal medical therapy. 1
• Early referral to HF specialist or advanced therapy programs should be considered in persistent hypotension with inability to optimize GDMT. 4