Can a sodium-glucose cotransporter-2 (SGLT-2) inhibitor be added to the treatment of acute heart failure?

SGLT2 Inhibitors in Acute Heart Failure Treatment

Yes, SGLT2 inhibitors should be added during acute heart failure hospitalization once patients are clinically stabilized, as they reduce mortality, worsening heart failure events, and improve quality of life when initiated early in the hospital setting. 1, 2

Evidence for In-Hospital Initiation

The strongest evidence comes from the EMPULSE trial (2022), which demonstrated that empagliflozin initiated during acute heart failure hospitalization resulted in significant clinical benefit (win ratio 1.36,95% CI 1.09-1.68, P=0.0054) across the hierarchical composite of death, heart failure events, and quality of life. 2

• A 2025 meta-analysis of seven randomized controlled trials confirmed that SGLT2 inhibitors initiated within the first five days of AHF hospitalization reduced all-cause mortality by 39% (RR=0.61,95% CI 0.40-0.95) and worsening heart failure by 41% (RR=0.59,95% CI 0.36-0.97). 3

• The SOLOIST-WHF trial demonstrated that sotagliflozin initiated during hospitalization (when transitioning from IV to oral diuretics) or shortly after discharge reduced cardiovascular deaths, hospitalizations, and urgent heart failure visits. 1, 4

Timing and Clinical Stability Criteria

Initiate SGLT2 inhibitors after initial stabilization but while still hospitalized—typically 1-5 days after admission—when patients meet specific stability criteria. 1, 2

Required Stability Parameters:

• No supplemental oxygen requirement 1
• Systolic blood pressure ≥100 mmHg 1
• No intravenous inotropes or vasodilators (nitrates acceptable) 1
• No increase in IV diuretics for 6 hours 5
• Clinically stable (median time to randomization in EMPULSE was 3 days from admission) 2

Benefits Across the Ejection Fraction Spectrum

SGLT2 inhibitors provide benefit regardless of ejection fraction category or diabetes status. 1, 2

• For HFrEF (LVEF ≤40%): Class I, Level A recommendation from the European Society of Cardiology to reduce cardiovascular death and heart failure hospitalizations. 5

• For HFmrEF and HFpEF (LVEF >40%): Class 2a, Level B-R recommendation from the American Heart Association/American College of Cardiology to decrease heart failure hospitalizations and cardiovascular mortality. 6, 7

• The EMPULSE trial showed consistent benefit in both acute de novo heart failure and decompensated chronic heart failure, regardless of ejection fraction or diabetes presence. 2

Specific Drug Selection and Dosing

Choose empagliflozin 10 mg daily or dapagliflozin 10 mg daily, as these have the strongest evidence from dedicated heart failure trials. 5

• No dose titration is required, unlike other heart failure medications. 5, 8
• Benefits occur within weeks of initiation, with empagliflozin showing 58% relative risk reduction at just 12 days. 5
• The 2024 ACC/AHA quality measures specify that SGLT2 inhibitors should be prescribed at hospital discharge for eligible patients. 6

Renal Function Considerations

Do not withhold SGLT2 inhibitors due to concerns about renal function—they can be used with eGFR as low as 20 mL/min/1.73m² for dapagliflozin. 5, 1

• An initial modest decline in eGFR (approximately -2 mL/min/1.73m² at day 15) is expected and does not indicate kidney injury. 5, 9
• By day 90, eGFR returns to similar levels as placebo, and investigator-reported acute renal failure was actually lower with empagliflozin (7.7%) versus placebo (12.1%). 9
• This transient eGFR decline provides long-term kidney protection and should not prompt discontinuation. 5, 1

Safety Profile and Monitoring

SGLT2 inhibitors have minimal impact on blood pressure, heart rate, or potassium levels, making them safe to combine with other guideline-directed medical therapy. 5, 8

Potential Adverse Effects:

• Genital mycotic infections (1.5-1.7%) 5, 1
• Urinary tract infections (2.3-2.7%) 5
• Volume depletion/hypotension (5.7%), especially in volume-depleted patients 5
• Diabetic ketoacidosis (rare, primarily in diabetic patients; significantly lower risk in non-diabetics) 5, 4

Monitoring Strategy:

• Consider reducing diuretic doses in patients at risk for hypovolemia 1
• Monitor renal function periodically (expect transient decline) 5, 9
• Assess for signs of volume depletion 5
• Serious adverse events were lower with empagliflozin (32.3%) versus placebo (43.6%) in EMPULSE 2

Integration with Other Heart Failure Therapies

SGLT2 inhibitors should be used alongside, not in place of, traditional diuretics for initial decongestion. 1

• They provide additive diuretic effect through a different mechanism than loop diuretics (blocking sodium-glucose reabsorption in proximal tubule versus loop of Henle). 4
• Unlike traditional diuretics, SGLT2 inhibitors address underlying neurohormonal activation contributing to congestion. 1
• They may facilitate use of other guideline-directed medical therapy components by reducing risks of hyperkalemia and fluid retention. 1

Critical Implementation Pitfall

The most important pitfall is delaying initiation until after discharge—deferring SGLT2 inhibitor initiation results in many eligible patients never receiving the medication within 1 year. 5

• The 2024 ACC/AHA quality measures now include SGLT2 inhibitor prescription at hospital discharge as a performance metric. 6
• Early initiation during hospitalization is critical, as benefits begin within days to weeks. 5, 1

Contraindications

Absolute Contraindications:

• eGFR <20 mL/min/1.73m² 6, 1
• Type 1 diabetes 6
• History of serious hypersensitivity to the specific SGLT2 inhibitor 5
• Pregnancy or breastfeeding 6

Relative Contraindications:

• Critically ill patients requiring mechanical ventilation or vasopressors 4
• Fasting patients (increased ketoacidosis risk) 4