SGLT2 Inhibitors Should NOT Be Held in Patients with Heart Failure and CKD
SGLT2 inhibitors are recommended and should be continued in patients with both heart failure and chronic kidney disease, as they reduce mortality, heart failure hospitalizations, and CKD progression across all stages of kidney function down to eGFR ≥20 mL/min/1.73 m² 1.
Primary Recommendation
- Continue SGLT2 inhibitors in all patients with heart failure and CKD who have eGFR ≥20 mL/min/1.73 m² 1
- For heart failure with reduced ejection fraction (LVEF ≤40%), SGLT2 inhibitors are Class 1 recommendation to reduce cardiovascular death and heart failure hospitalization 1
- For heart failure with preserved ejection fraction (LVEF >40%), SGLT2 inhibitors provide Class 2a benefit for decreasing heart failure hospitalizations 1
Evidence Supporting Continued Use
Cardiovascular Benefits
- EMPEROR-Reduced and EMPEROR-Preserved trials demonstrated efficacy at eGFR levels as low as 20 mL/min/1.73 m² in patients with heart failure 1
- In very high-risk CKD patients with heart failure, SGLT2 inhibitors decrease all-cause mortality by 48 fewer deaths per 1000 patients 1
- Cardiovascular mortality is reduced by 10 fewer deaths per 1000 patients in this population 1
Kidney Protection
- SGLT2 inhibitors reduce kidney failure by 58 fewer events per 1000 patients in very high-risk CKD 1, 2
- These agents slow CKD progression independent of glycemic control through reduction in intraglomerular pressure 1
- The kidney-protective effects persist even when eGFR falls below the level where glucose-lowering efficacy diminishes 1
Specific eGFR Thresholds
When to Continue
- Once initiated, continue SGLT2 inhibitors even if eGFR falls below 20 mL/min/1.73 m², unless kidney replacement therapy is initiated 1
- For patients with type 2 diabetes and CKD, use SGLT2 inhibitors down to eGFR >20 mL/min/1.73 m² 1
- For patients with heart failure (regardless of diabetes status), continue therapy at eGFR ≥20 mL/min/1.73 m² 1
When to Temporarily Hold (Not Permanently Discontinue)
- Withhold during prolonged fasting, surgery, or critical medical illness when patients are at greater risk for ketosis 1
- Implement sick day protocols: hold during acute illness 2
- These are temporary holds, not permanent discontinuation
Managing the Initial eGFR Decline
Expected Changes
- Expect an initial reversible decline in eGFR of 3-5 mL/min/1.73 m² within the first 4 weeks 2
- This hemodynamic decline is not a reason to discontinue therapy 1
- SGLT2 inhibitor initiation does not necessitate alteration of frequency of CKD monitoring 1
Monitoring Protocol
- Check serum creatinine within 2-4 weeks of initiation 1
- The reversible eGFR decrease is generally not an indication to discontinue therapy 1
Practical Implementation
Volume Management
- Consider proactive dose reduction of loop diuretics in patients at high risk for volume depletion 2
- For patients on concomitant diuretics, decrease the diuretic dose and counsel about symptoms of volume depletion 1
- Monitor for modest volume contraction, blood pressure reduction, and weight loss 1
Combination Therapy
- Start SGLT2 inhibitors on top of background therapy with ACE inhibitor or ARB 2
- SGLT2 inhibitors can be added to RAS inhibitors and other heart failure medications 1
- More than 80% of participants in heart failure trials were receiving RAS inhibitors when SGLT2 inhibitors were added 1
Agent Selection for Heart Failure and CKD
Preferred Agents
- For heart failure with proteinuria: empagliflozin or dapagliflozin are preferred 2
- All three major SGLT2 inhibitors (canagliflozin, dapagliflozin, empagliflozin) have demonstrated consistent efficacy 2
- For diabetic kidney disease with heart failure, any of the three agents can be used 2
Common Pitfalls to Avoid
Do NOT Discontinue For:
- Initial eGFR decline of 3-5 mL/min/1.73 m² - this is expected and hemodynamic 1, 2
- eGFR falling below 30 mL/min/1.73 m² - continue down to 20 mL/min/1.73 m² 1
- Reduced glucose-lowering efficacy at lower eGFR - cardiovascular and kidney benefits persist 1
Only Discontinue When:
- Kidney replacement therapy (dialysis) is initiated - insufficient evidence for benefit on dialysis 3
- Intolerable adverse effects occur 1
- Patient develops diabetic ketoacidosis (rare) 1
Risk Stratification for Strength of Recommendation
Strong Recommendation (Very High Risk)
- Patients with eGFR 20-45 mL/min/1.73 m² AND heart failure receive strong recommendation for SGLT2 inhibitors 1
- This population has high certainty of survival benefit and reduced kidney failure 1