What is the optimal treatment plan for a patient with heart failure with reduced ejection fraction (HFrEF) and impaired renal function, specifically with an estimated glomerular filtration rate (eGFR) of less than 30?

Treatment Plan for Heart Failure with Reduced Ejection Fraction and eGFR <30

All four pillars of guideline-directed medical therapy (GDMT) for HFrEF should be initiated in patients with eGFR <30, with specific modifications: SGLT2 inhibitors (dapagliflozin if eGFR ≥20 or empagliflozin if eGFR ≥20), beta-blockers at full target doses, ACE inhibitors/ARBs/ARNI with careful monitoring, and mineralocorticoid receptor antagonists (MRAs) are contraindicated when eGFR <30 per current guidelines but may be continued if already established with intensive monitoring. 1

Core GDMT Components

SGLT2 Inhibitors (First Priority)

• Initiate SGLT2 inhibitors immediately as they are the safest and most effective option in severe renal impairment 1
• Dapagliflozin 10 mg daily can be used if eGFR ≥20 mL/min/1.73 m² 2, 3
• Empagliflozin 10 mg daily can be used if eGFR ≥20 mL/min/1.73 m² 2, 3
• No dose adjustment or uptitration required, and they do not affect blood pressure, heart rate, or potassium levels 1
• Expect a mild, transient drop in eGFR after initiation, but long-term kidney protection is maintained 1, 3
• Continue therapy even if eGFR declines further, as clinical benefits persist 3

Beta-Blockers

• Use one of three evidence-based beta-blockers: bisoprolol, carvedilol, or sustained-release metoprolol succinate 1
• Titrate to target dose (bisoprolol 10 mg daily, carvedilol 25 mg twice daily, or metoprolol succinate 200 mg daily) or maximally tolerated dose 1, 2
• Only bisoprolol may accumulate in renal impairment, but still titrate to target based on clinical response 2
• No specific dose reduction required for eGFR <30 2

Renin-Angiotensin System Inhibition

• ARNI (sacubitril/valsartan) is NOT recommended when eGFR <30 mL/min/1.73 m² 2, 4
• Use ACE inhibitors or ARBs instead when eGFR <30 1, 2
• Start at low doses and monitor renal function and potassium closely (every 1-2 weeks initially) 2, 3
• Accept an initial decline in eGFR up to 30% if patient remains clinically stable—do not discontinue therapy 3
• If eGFR declines but stabilizes and clinical condition improves, continue therapy 3

Mineralocorticoid Receptor Antagonists (MRAs)

• Current guidelines state MRAs are recommended only if eGFR >30 mL/min/1.73 m² and potassium <5.0 mEq/L 1
• However, recent evidence shows MRAs remain effective and provide substantial absolute risk reduction even when eGFR declines to <30 5
• If patient is already on an MRA when eGFR drops below 30, consider continuing with:
  • Very low starting dose (6.25-12.5 mg spironolactone daily or every other day) 2
  • Intensive monitoring of potassium (weekly initially, then every 2 weeks) and renal function 1, 2
  • Accept risk of severe hyperkalemia (>6.0 mmol/L) as 3 additional cases per 100 person-years, balanced against 21 fewer cardiovascular deaths/HF hospitalizations per 100 person-years 5
• Do not automatically discontinue MRA if eGFR declines to <30—the absolute benefit is greatest in this highest-risk population 5

Diuretic Management

• Use loop diuretics as needed to control congestion 1
• Higher doses of loop diuretics are strongly associated with worse renal function but are necessary for symptom control 6
• SGLT2 inhibitors enhance diuretic efficacy and may reduce the need for loop diuretic intensification 1

Monitoring Strategy

• Check potassium and renal function weekly for first 2-4 weeks after initiating or uptitrating GDMT, then every 2 weeks until stable 1, 2
• Accept eGFR decline up to 30% from baseline if clinically stable 3
• Monitor for hyperkalemia (target <5.0 mEq/L for MRA initiation, but can tolerate up to 5.5 mEq/L if already established) 1, 5
• Do not discontinue life-saving therapies for asymptomatic laboratory changes alone 3, 5

Implementation Sequence

• Start all four medication classes simultaneously at low doses rather than sequential uptitration 1
• Prioritize SGLT2 inhibitors and beta-blockers first as they have the most favorable safety profile in severe CKD 1, 2
• Add ACE inhibitor/ARB second with close monitoring 2, 3
• Consider MRA last, only if potassium <5.0 mEq/L and with intensive monitoring, or continue if already established 1, 5

Critical Pitfalls to Avoid

• Do not withhold SGLT2 inhibitors due to low eGFR—they are safe and effective down to eGFR 20 1, 2, 3
• Do not automatically discontinue MRAs when eGFR drops below 30 if patient is already tolerating therapy—the absolute benefit is greatest in this population 5
• Do not stop ACE inhibitors/ARBs for asymptomatic eGFR decline up to 30%—renal function often stabilizes and clinical benefits persist 3
• Avoid metformin if eGFR <30 due to lactic acidosis risk 1
• Do not use sacubitril/valsartan when eGFR <30 2, 4