What is the initial treatment approach for patients diagnosed with heart failure, particularly those with reduced ejection fraction?

Initial Treatment Approach for Heart Failure with Reduced Ejection Fraction

For patients diagnosed with heart failure with reduced ejection fraction (HFrEF), the initial treatment should include a combination of SGLT2 inhibitors and mineralocorticoid receptor antagonists (MRAs) as first-line therapy, followed by beta-blockers and renin-angiotensin system inhibitors, with careful dose titration to maximize survival benefits. 1

Core Medication Classes for HFrEF

First-Line Medications

• SGLT2 inhibitors (dapagliflozin 10 mg daily or empagliflozin 10 mg daily) should be initiated early as they have minimal impact on blood pressure while providing significant mortality benefits 1
• Mineralocorticoid receptor antagonists (spironolactone 12.5-25 mg daily or eplerenone 25 mg daily) should be started concurrently with SGLT2 inhibitors in patients with eGFR >30 ml/min/1.73m² 1, 2

Second-Line Medications

• Beta-blockers (carvedilol, metoprolol succinate, or bisoprolol) should be initiated at low doses and gradually titrated up, particularly when heart rate is >70 bpm 1
• Renin-angiotensin system inhibitors:
  • Sacubitril/valsartan (ARNI) starting at 24/26 mg or 49/51 mg twice daily, titrating to 97/103 mg twice daily as tolerated 3
  • If ARNI is not tolerated, use ACE inhibitors (e.g., enalapril, lisinopril) or ARBs (e.g., valsartan, candesartan) if ACE inhibitors cause cough or angioedema 1

Medication Initiation and Titration Strategy

1. Start with low doses and titrate gradually to target doses shown to be effective in clinical trials 1, 4
2. Sequence of initiation when blood pressure is adequate:
   • Begin with SGLT2 inhibitor and MRA simultaneously 1
   • Add beta-blocker if heart rate >70 bpm 1
   • Add ARNI or ACE inhibitor/ARB at low dose and titrate up 1
3. For patients with low blood pressure (<90 mmHg):
   • Start with SGLT2 inhibitor and MRA as they have minimal BP-lowering effects 1
   • Consider selective β₁ receptor blockers (metoprolol succinate or bisoprolol) rather than non-selective beta-blockers with vasodilatory properties (carvedilol) 1
   • If beta-blockers cannot be tolerated, consider ivabradine for patients in sinus rhythm with HR >70 bpm 1

Diuretic Therapy

• Loop diuretics should be administered for symptom relief in patients with fluid retention 1, 4
• Diuretic dose should be adjusted based on volume status and may need to be reduced when initiating ACE inhibitors 4, 1
• Avoid excessive diuresis before starting ACE inhibitors 4, 1

Monitoring and Follow-up

• Monitor renal function and electrolytes 1-2 weeks after initiation and each dose increment of ACE inhibitors, ARBs, ARNIs, and MRAs 1, 4
• For patients with low BP, use small incremental dose increases and up-titrate one drug at a time with close follow-up 1
• Consider spacing out medications throughout the day to reduce synergistic hypotensive effects 1

Special Considerations

• In patients with eGFR <30 ml/min/1.73m², reduce or avoid MRAs and adjust RAS inhibitor dosing 1
• For patients with hyperkalemia (K+ >5.0 mEq/L), reduce MRA dose first 1
• For patients with HR <60 bpm, prioritize RAS inhibitors over beta-blockers 1

Common Pitfalls to Avoid

• Undertreatment: Many patients remain on suboptimal doses of medications initiated at the time of diagnosis 1, 5
• Failure to titrate: Forced titration strategies used in clinical trials are infrequently followed in clinical practice 1, 5
• Inappropriate medication selection: Avoid NSAIDs, most antiarrhythmic drugs, and calcium channel blockers (verapamil, diltiazem, and short-acting dihydropyridines) in HFrEF patients 1, 6
• Inadequate follow-up: Patients benefit from specialized heart failure clinic care, which is associated with higher rates of GDMT initiation 5, 7