Which medication used for heart failure with reduced ejection fraction is contraindicated in patients with end‑stage renal disease (chronic renal failure grade 5)?

SGLT2 Inhibitors Cannot Be Used in Chronic Renal Failure Grade 5

Among the guideline-directed medical therapies for HFrEF, SGLT2 inhibitors (specifically empagliflozin and dapagliflozin) are contraindicated or have very limited data in patients with end-stage renal disease (chronic renal failure grade 5/eGFR <15 mL/min/1.73 m² or on dialysis).

Evidence-Based Renal Function Thresholds

The 2021 ACC Expert Consensus provides explicit guidance on SGLT2 inhibitor use based on renal function 1:

• Dapagliflozin: Requires eGFR >30 mL/min/1.73 m² before initiation
• Empagliflozin: Requires eGFR >20 mL/min/1.73 m² (EMPEROR-Reduced) or >60 mL/min/1.73 m² (older labeling) before initiation
• Both agents are contraindicated in patients on dialysis 1, 2

The 2021 Canadian guidelines reinforce this, noting that EMPEROR-Reduced excluded patients with eGFR <20 mL/min/1.73 m² and DAPA-HF excluded those with eGFR <30 mL/min/1.73 m², with "very limited" data supporting use in patients with HFrEF and eGFR <30 mL/min/1.73 m² 3.

Why Other HFrEF Medications Can Be Used

In contrast, other core HFrEF therapies have more flexibility in stage 5 CKD:

ACE Inhibitors/ARBs

• Can be used with careful monitoring, though dose adjustments may be needed
• Not absolutely contraindicated in dialysis patients 4, 5

Sacubitril/Valsartan (ARNI)

• Not recommended when eGFR <30 mL/min/1.73 m² 1, 4
• PARADIGM-HF excluded patients with eGFR <30 mL/min/1.73 m²
• However, emerging observational data suggest potential use in dialysis patients, though this remains off-label 6, 5

Beta-Blockers

• No renal-based contraindications for carvedilol or metoprolol succinate
• Bisoprolol may accumulate but can still be titrated to target dose with monitoring 4

Mineralocorticoid Receptor Antagonists (MRAs)

• Generally recommended when eGFR ≥30 mL/min/1.73 m²
• Can be used cautiously at lower doses (6.25-12.5 mg daily or every other day) in advanced CKD with close potassium monitoring 4, 7
• Not absolutely contraindicated in stage 5 CKD, though requires intensive monitoring

Clinical Algorithm for Stage 5 CKD with HFrEF

Avoid:

• SGLT2 inhibitors (dapagliflozin, empagliflozin) - primary answer to your question
• Sacubitril/valsartan (eGFR <30 contraindication)

Use with caution and monitoring:

• ACE inhibitors or ARBs (monitor potassium, renal function)
• Beta-blockers (all three evidence-based agents can be used)
• MRAs at reduced doses (if potassium can be managed)
• Loop diuretics (often required for volume management)

Important Caveats

The SGLT2 inhibitor contraindication in stage 5 CKD is based on:

1. Mechanism of action: These drugs require functioning nephrons to exert their glucose-lowering and natriuretic effects
2. Trial exclusion criteria: Patients with severe renal impairment were systematically excluded from landmark trials
3. Safety concerns: Risk of volume depletion, acute kidney injury, and lack of efficacy data in this population 3, 2

The 2022 Canadian guidelines explicitly state that canagliflozin and dapagliflozin are contraindicated in patients undergoing dialysis, and empagliflozin is contraindicated when eGFR <20 mL/min/1.73 m² 2.