What is the initial treatment for a patient with heart failure and mildly reduced Ejection Fraction (EF)?

Initial Treatment for Heart Failure with Mildly Reduced Ejection Fraction

For patients with heart failure and mildly reduced ejection fraction (EF), the initial treatment should include an ACE inhibitor (or ARB), beta-blocker, mineralocorticoid receptor antagonist (MRA), and SGLT2 inhibitor, with careful dose titration based on blood pressure tolerance. 1

First-Line Medications

• ACE inhibitors (or ARBs if ACE inhibitors are contraindicated) should be started as soon as possible in patients with mildly reduced EF, with blood pressure and renal function monitoring 2
• Beta-blockers should be initiated at low doses and gradually titrated to target doses as tolerated, particularly after patient stabilization 2
• Mineralocorticoid receptor antagonists (MRAs) such as spironolactone or eplerenone should be started as soon as possible, as they have minimal effect on blood pressure while providing significant benefits 2
• SGLT2 inhibitors should be considered early in treatment as they have minimal blood pressure-lowering effects while providing mortality benefit 2, 1

Implementation Strategy

• For patients with low blood pressure, start with medications that have the least effect on BP (SGLT2 inhibitors and MRAs) before introducing ACE inhibitors/ARBs and beta-blockers 2
• Consider starting with low-dose sacubitril/valsartan (24/26 mg to 49/51 mg twice daily) instead of an ACE inhibitor in appropriate patients, as it provides superior reduction in heart failure hospitalization and death 1, 3
• If sacubitril/valsartan cannot be tolerated, use a low-dose ACE inhibitor such as enalapril, starting at 2.5 mg twice daily and titrating up as tolerated 4
• For beta-blockers, selective β₁ receptor blockers may be preferred due to their lesser BP-lowering effect compared to non-selective beta-blockers 2

Dose Titration

• Start with low doses of multiple medications simultaneously rather than waiting to reach target doses of one medication before starting another 1
• Gradually increase to target doses over 6-12 weeks, with close monitoring of symptoms, blood pressure, and renal function 1
• If beta-blockers are not well tolerated hemodynamically, ivabradine may be considered as an alternative, especially if heart rate remains elevated (>70 bpm) 2, 5
• Diuretics should be adjusted according to volume status, avoiding overdiuresis which can lead to hypotension 5

Monitoring Parameters

• Regular assessment of symptoms, functional capacity, blood pressure, renal function, electrolytes, heart rate, and rhythm is essential 1
• Renal function and electrolytes should be checked 1-2 weeks after each dose increment, at 3 months, and subsequently at 6-month intervals 2
• Daily monitoring of vital signs including blood pressure, heart rate, and weight is recommended during medication adjustments 5

Common Pitfalls to Avoid

• Underutilization of guideline-directed medical therapy and inadequate dose titration are common issues in heart failure management 1
• Avoid NSAIDs due to potential worsening of renal function and counteraction of beneficial effects of heart failure medications 1
• Excessive diuresis before initiating ACE inhibitors/ARBs can lead to hypotension; consider reducing diuretic dose temporarily when starting these medications 2
• Inappropriate discontinuation of medications due to mild, asymptomatic hypotension should be avoided 1

Special Considerations

• In patients with persistent low blood pressure, consider a sequential approach: start SGLT2 inhibitor and MRA first, followed by beta-blocker (if HR >70 bpm) or ACE inhibitor/ARB/ARNI at low dose 2
• For patients not reaching at least 50% of recommended doses of ACE inhibitors/ARBs and beta-blockers, there is a significantly increased risk of death and/or heart failure hospitalization 6
• Patients reaching 50-99% of recommended doses have similar outcomes to those reaching ≥100%, suggesting that achieving at least moderate doses is crucial 6