What is the role of Jardiance (empagliflozin) in treating heart failure?

Jardiance (Empagliflozin) for Heart Failure

Empagliflozin should be initiated in all symptomatic heart failure patients regardless of ejection fraction or diabetes status, as it reduces heart failure hospitalizations and cardiovascular death across the entire spectrum of heart failure. 1, 2

Foundational Therapy Recommendation

Empagliflozin is recommended by the American College of Cardiology as foundational therapy for congestive heart failure and should be started in all symptomatic patients with any ejection fraction. 1 This represents a paradigm shift where SGLT2 inhibitors are no longer optional add-ons but core components of heart failure management. 3, 2

Evidence Across Heart Failure Phenotypes

Heart Failure with Reduced Ejection Fraction (HFrEF, LVEF ≤40%)

• The EMPEROR-Reduced trial demonstrated a 21% reduction in the composite outcome of cardiovascular death or hospitalization for heart failure (HR 0.79,95% CI 0.69-0.90; P < 0.001) in 3,730 patients with HFrEF. 3, 2
• Benefits were evident as early as 12 days after randomization and sustained throughout follow-up. 4
• Empagliflozin reduced total heart failure hospitalizations requiring intensive care by 33% (HR 0.67,95% CI 0.50-0.90) and those requiring vasopressors or mechanical intervention by 36% (HR 0.64,95% CI 0.47-0.87). 4

Heart Failure with Preserved Ejection Fraction (HFpEF, LVEF >40%)

• The EMPEROR-Preserved trial of 5,988 adults with NYHA class I-IV heart failure and LVEF >40% showed a 21% reduction in cardiovascular death or heart failure hospitalization over 26.2 months. 1
• Benefits were consistent regardless of diabetes status at baseline. 1
• For patients with mid-range ejection fraction (HFmrEF, LVEF 41-49%), empagliflozin receives a Class 2a recommendation with similar 21% risk reduction. 1

Clinical Benefits Beyond Hospitalization

• Empagliflozin reduced the combined risk of death, hospitalization, or emergent/urgent heart failure visits requiring IV treatment by 24% (HR 0.76,95% CI 0.67-0.87). 4
• Patients were 67% less likely to require intensification of diuretics (297 vs 414 patients, HR 0.67,95% CI 0.56-0.78). 4
• Patients were 20-40% more likely to experience improvement in NYHA functional class and 20-40% less likely to experience worsening, with effects apparent at 28 days. 4
• Quality of life scores showed modest but significant improvement at 52 weeks. 1

Renal Protection

• Empagliflozin decreased the slope of eGFR decline across all heart failure phenotypes and reduced the risk of composite renal outcomes by 50% in the EMPA-REG OUTCOME trial. 1
• Renal benefits are observed even in patients with eGFR as low as 25 mL/min/1.73 m². 3
• The drug preserves kidney function rather than causing adverse renal effects. 3

Practical Implementation

Dosing and Initiation

• The standard dose is empagliflozin 10 mg once daily, added to guideline-directed medical therapy (GDMT), not as monotherapy. 1
• No titration is required, making it simpler to implement than traditional heart failure medications. 5
• The American College of Cardiology recommends initiating during heart failure hospitalization in stabilized patients, as deferring initiation results in many eligible patients never receiving the medication within 1 year. 3

Monitoring Requirements

• Monitor renal function regularly when initiating empagliflozin, particularly in patients with baseline kidney disease. 1
• Assess volume status regularly due to diuretic effects of SGLT2 inhibitors. 1
• Monitor for symptomatic hypotension, especially in elderly patients, those with renal impairment, low systolic blood pressure, or those on diuretics. 2
• Assess for signs/symptoms of ketoacidosis, particularly during illness or fasting, including euglycemic ketoacidosis. 2

Safety Considerations

• Empagliflozin is contraindicated in patients on dialysis. 1
• Genital tract infections occur more frequently with empagliflozin (1.7%) compared to placebo (0.6%), though overall side effects are similar. 6
• Monitor for euglycemic ketoacidosis, genital and soft tissue infections, and volume depletion, especially when combined with diuretics. 3
• The drug has minimal blood pressure effects and no excess risk of symptomatic hypotension compared to placebo. 3

Mechanism and Independence from Diabetes

• Benefits of empagliflozin in heart failure are independent of glucose-lowering effects, representing direct cardiovascular benefit. 3, 2
• The drug is effective regardless of diabetes status, with similar efficacy in patients with and without diabetes. 1, 2
• Empagliflozin acts as an enabler for other heart failure drugs by reducing the risk of hyperkalemia. 5

Special Populations

Post-Myocardial Infarction

• In the EMPACT-MI trial of 6,522 patients with acute MI and left ventricular dysfunction or congestion, empagliflozin reduced first HF hospitalization by 23% (HR 0.77,95% CI 0.60-0.98) and total HF hospitalizations by 33% (rate ratio 0.67,95% CI 0.51-0.89). 7
• Benefits were consistent across ischemic and nonischemic causes of heart failure. 8

Interaction with Existing GDMT

• Continue existing GDMT including ACE inhibitors, ARBs, beta-blockers, and mineralocorticoid receptor antagonists, as empagliflozin provides additive benefit. 3
• Empagliflozin provides incremental benefit even in patients already on optimal GDMT, reducing the primary outcome by 26% (HR 0.74,95% CI 0.59-0.93). 3

Common Pitfalls to Avoid

• Do not delay initiation waiting for "optimization" of other medications—start empagliflozin early in the treatment course. 3
• Do not discontinue empagliflozin due to mild eGFR decline, as the drug preserves long-term kidney function. 1, 3
• Do not withhold in patients without diabetes—the cardiovascular benefits are independent of glycemic effects. 1, 2
• Do not use as monotherapy; always add to existing GDMT. 1