What is the recommended initial Guideline-Directed Medical Therapy (GDMT) for a patient with impaired renal function?

SGLT2 Inhibitors Can Be Started in Patients with Elevated Creatinine and Offer Significant Benefits in Heart Failure Management

SGLT2 inhibitors are the preferred GDMT to initiate in patients with elevated creatinine, as they can be safely used with eGFR as low as 20-30 mL/min/1.73m² and provide renal protection despite an initial mild decrease in GFR. 1

GDMT Options Based on Renal Function

SGLT2 Inhibitors

• Can be initiated with moderate kidney dysfunction:
  • Empagliflozin: eGFR ≥30 mL/min/1.73m²
  • Dapagliflozin: eGFR ≥20 mL/min/1.73m² 1
• Unique advantages in renal impairment:
  • No dose adjustment required
  • No effect on blood pressure, heart rate, or potassium levels
  • Provides long-term kidney protection despite initial transient GFR drop
  • Benefits occur within weeks of initiation 1
  • Reduces need for diuretic intensification
  • May facilitate use of MRAs by reducing hyperkalemia risk 1

ACE Inhibitors/ARBs

• Can be used with caution in renal impairment:
  • Start at lower doses when eGFR <45 mL/min/1.73m² 1
  • Lisinopril: Reduce initial dose by half when creatinine clearance ≤30 mL/min 2
  • Losartan: No dose adjustment needed unless patient is volume depleted 3
• Monitoring requirements:
  • Check GFR and potassium within 1 week of starting or dose escalation
  • Temporary suspension during intercurrent illness or IV contrast
  • Consider discontinuation if creatinine rises >30% 1

Beta-Blockers

• Reduce dose by 50% when eGFR <30 mL/min/1.73m² 1
• Should be continued during hospitalization for heart failure unless hemodynamically unstable 1

MRAs (Mineralocorticoid Receptor Antagonists)

• Use with caution in renal impairment due to hyperkalemia risk
• Monitor potassium levels closely
• May be better tolerated when combined with SGLT2 inhibitors 1

Implementation Strategy for GDMT in Renal Impairment

1. First-line approach: Start with SGLT2 inhibitor if eGFR ≥20-30 mL/min/1.73m² 1

   • No dose adjustment needed
   • Monitor for initial mild decrease in eGFR (expected and not harmful)

2. Second-line approach: Add ACEi/ARB at reduced dose if eGFR ≥30 mL/min/1.73m² 1, 2

   • Start at 50% of normal dose
   • Monitor creatinine and potassium within 1 week
   • Accept up to 30% increase in creatinine if stable thereafter

3. Third-line approach: Add beta-blocker at reduced dose if eGFR <30 mL/min/1.73m² 1

   • Use 50% of normal dose
   • Titrate based on heart rate and blood pressure response

4. Fourth-line approach: Consider MRA with careful monitoring if needed for optimal HF management

Monitoring Recommendations

• Serum electrolytes, urea nitrogen, and creatinine should be measured during titration of HF medications, including diuretics 1
• For ACEi/ARB: Check renal function and potassium within 1 week of initiation or dose change 1
• For SGLT2 inhibitors: Expect and accept mild initial decrease in eGFR (≤15%) 4
• Continue GDMT despite mild decreases in renal function or asymptomatic reduction of blood pressure during HF hospitalization 1

Common Pitfalls to Avoid

1. Unnecessary discontinuation: Mild increases in creatinine (up to 30%) after starting ACEi/ARB are expected and should not prompt discontinuation 1

2. Failure to initiate: Only 33% of eligible HFrEF patients receive MRA therapy, and 42% receive no GDMT within 30 days post-hospitalization 1

3. Undertreatment: Patients with renal dysfunction often receive suboptimal GDMT doses despite evidence showing benefits in this population 5

4. Diuretic-induced volume depletion: Most common avoidable reason for creatinine rise with RAS modulators 1

5. Ignoring the opportunity of hospitalization: Hospitalization for HF is a critical opportunity to initiate and optimize GDMT 1

Recent evidence strongly supports that GDMT benefits are consistent in patients with and without chronic kidney disease, with similar risk reductions for cardiovascular death and HF hospitalization in both groups 5. The key is to start with appropriate medications and doses based on renal function, then monitor closely while accepting expected mild changes in renal parameters.