What is the role of SGLT2 (sodium-glucose cotransporter 2) inhibitors in acute decompensated heart failure?

Role of SGLT2 Inhibitors in Acute Decompensated Heart Failure

SGLT2 inhibitors should be initiated as early as safely possible in patients with acute decompensated heart failure (ADHF) to improve clinical outcomes, regardless of ejection fraction or diabetes status. 1

Evidence for SGLT2 Inhibitors in ADHF

Clinical Benefits

• SGLT2 inhibitors reduce the combined endpoint of worsening heart failure, rehospitalization for heart failure, or death when initiated during hospitalization for ADHF 2
• The SOLOIST-WHF trial demonstrated that early initiation of sotagliflozin (an SGLT1/2 inhibitor) in patients hospitalized for worsening heart failure reduced the primary endpoint of cardiovascular deaths, hospitalizations, and urgent visits for heart failure 1
• SGLT2 inhibitors enhance decongestion therapy and lead to improved and sustained decongestion in ADHF patients 3
• Continuing SGLT2 inhibitors at discharge in patients hospitalized for ADHF is associated with fewer heart failure rehospitalizations compared to discontinuation 4

Physiological Effects

• SGLT2 inhibitors significantly increase urinary output in ADHF patients, supporting their role in decongestion 2
• Unlike traditional diuretics, SGLT2 inhibitors address the underlying neurohormonal activation that contributes to congestion in heart failure 1
• SGLT2 inhibitors provide renal protection, which is particularly important in ADHF where worsening kidney function is common 3

Implementation in Clinical Practice

Timing of Initiation

• SGLT2 inhibitors should be initiated after initial stabilization (between 24 hours and 5 days after admission) as demonstrated in the EMPULSE trial 5
• Early initiation appears both practical and beneficial, leading to improved outcomes while maintaining a favorable safety profile 3

Patient Selection

• SGLT2 inhibitors can be used regardless of ejection fraction and diabetes status 5, 1
• Patients should be clinically stable prior to initiation (no supplemental oxygen requirement, systolic blood pressure ≥100 mmHg, and no need for intravenous inotropes or vasodilators other than nitrates) 1

Safety Considerations

• SGLT2 inhibitors are generally safe and well-tolerated in ADHF, with no adverse effects on blood pressure or renal function 2
• Consider reducing diuretic doses in patients at risk for hypovolemia 1
• Implement "sick day" protocols, including temporary discontinuation during acute illness with nausea, vomiting, or diarrhea 1
• Monitor for potential risks including genital mycotic infections and, less commonly, diabetic ketoacidosis 1

Integration with Other Heart Failure Therapies

Complementary Role with Diuretics

• SGLT2 inhibitors should be used alongside, not in place of, traditional diuretics for initial decongestion in ADHF 1
• Once accumulated volume is no longer a major clinical problem, focus should shift to neurohormonal blockade (including SGLT2 inhibitors) with the lowest possible dose of diuretics 1

Part of Comprehensive GDMT

• SGLT2 inhibitors are now considered part of guideline-directed medical therapy (GDMT) for heart failure across the spectrum of ejection fraction 1
• The 2022 AHA/ACC/HFSA guidelines recognize SGLT2 inhibitors as one of the four medication classes that comprise GDMT for heart failure with reduced ejection fraction 1
• European Society of Cardiology quality indicators now include SGLT2 inhibitor prescription as a main quality indicator for heart failure patients, independent of ejection fraction 1

Clinical Pearls and Pitfalls

• Avoid delaying SGLT2 inhibitor initiation due to concerns about renal function; these medications are renoprotective and can be used in patients with eGFR as low as 20 mL/min/1.73m² 1
• Do not discontinue SGLT2 inhibitors at the time of ADHF hospitalization in patients already taking them, as continuation is associated with better outcomes 4
• The initial small decline in eGFR (3-5 mL/min/1.73m²) commonly seen with SGLT2 inhibitor initiation is expected and typically stabilizes during ongoing therapy 1
• SGLT2 inhibitors may facilitate the use of other GDMT components by reducing risks of hyperkalemia and fluid retention 1