Is Jardiance (empagliflozin) 10mg effective for treating heart failure?

Jardiance (Empagliflozin) 10mg for Heart Failure

Empagliflozin 10mg daily is highly effective for treating heart failure across the entire spectrum of ejection fractions (HFrEF, HFmrEF, and HFpEF), reducing cardiovascular death or heart failure hospitalization by 21% regardless of diabetes status. 1, 2

Evidence-Based Recommendation

The 2022 ACC/AHA/HFSA guidelines give empagliflozin a Class 2a recommendation for heart failure with mildly reduced ejection fraction (HFmrEF) and support its use across all heart failure phenotypes. 3 The American College of Cardiology strongly recommends SGLT2 inhibitors for all patients with symptomatic heart failure regardless of ejection fraction or diabetes status. 1

Clinical Trial Evidence by Heart Failure Type

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

• EMPEROR-Reduced enrolled 3,730 patients with HFrEF and demonstrated that empagliflozin 10mg daily reduced the composite outcome of cardiovascular death or hospitalization for heart failure by 21% (HR 0.79 [95% CI 0.69-0.90]; P < 0.001). 1, 2, 4
• The benefit reached statistical significance at just 12 days after randomization, indicating rapid onset of therapeutic effect. 4
• Empagliflozin reduced total heart failure hospitalizations requiring intensive care by 33% (HR 0.67; 95% CI 0.50-0.90; P=0.008) and those requiring vasopressors or inotropes by 36% (HR 0.64; 95% CI 0.47-0.87; P=0.005). 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 and maintained long-term. 4

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

• EMPEROR-Preserved enrolled 5,988 patients with HFpEF and showed empagliflozin 10mg daily reduced cardiovascular death or heart failure hospitalization by 21% (HR 0.79 [95% CI 0.69-0.90]), driven primarily by a 29% reduction in heart failure hospitalization. 3, 2, 5
• The benefit reached statistical significance at 18 days after randomization. 5
• Empagliflozin reduced heart failure hospitalizations requiring intensive care by 29% (HR 0.71; 95% CI 0.52-0.96; P=0.028). 5
• The benefit on total heart failure hospitalizations was similar in patients with ejection fraction 40-49% and 50-59%, but attenuated at higher ejection fractions (>62.5%). 3, 5

Heart Failure with Mildly Reduced Ejection Fraction (HFmrEF, LVEF 41-49%)

• In the subgroup of 1,983 patients with LVEF 41-49% from EMPEROR-Preserved, empagliflozin reduced the primary composite endpoint with similar efficacy to the overall trial population. 3
• Patients with LVEF on the lower end of the 41-49% spectrum appear to respond similarly to patients with HFrEF. 3

Diabetes-Independent Benefits

• The cardiovascular benefits of empagliflozin occur regardless of diabetes status—49% of EMPEROR-Reduced patients had diabetes, and the hazard ratio for the primary outcome was identical in patients with and without diabetes (HR 0.79 vs 0.78; P-interaction=0.92). 6
• The benefits are independent of glucose-lowering effects and represent direct cardiovascular benefit through mechanisms beyond glycemic control. 1, 2
• Baseline hemoglobin A1c did not modify treatment effects (P-interaction=0.26). 6

Timing of Initiation

ACC Expert Consensus documents recommend in-hospital initiation of empagliflozin during heart failure hospitalization in stabilized patients (systolic blood pressure >100 mmHg, no IV vasodilators or increase in IV loop diuretics in 6 hours, no IV inotropes in 24 hours). 3 The EMPULSE trial specifically evaluated this approach in 530 hospitalized patients on days 2-5 of admission. 3

• Deferring initiation until after discharge is associated with a high likelihood that eligible patients will never receive the medication within 1 year. 1
• FDA drug labels do not reference location of care, and in-hospital versus outpatient status does not impact eligibility. 3

Additive Benefit to Existing Therapy

• Empagliflozin provides incremental benefit regardless of whether patients are already on optimal guideline-directed medical therapy (ACE inhibitors/ARBs, beta-blockers, and mineralocorticoid receptor antagonists). 1
• Continue existing GDMT as empagliflozin provides additive benefit rather than replacing other therapies. 1
• Fewer patients in the empagliflozin group required intensification of diuretics compared to placebo (297 versus 414; HR 0.67; 95% CI 0.56-0.78; P<0.0001 in HFrEF). 4

Renal Considerations

• Empagliflozin preserves kidney function rather than causing adverse renal effects, with benefits observed even in patients with eGFR as low as 20 mL/min/1.73 m² (EMPULSE trial criteria). 3
• The drug attenuates eGFR decline during treatment, with more pronounced effects in patients with diabetes (1.77 vs 0.98 mL/min/1.73m² in patients without diabetes; P-interaction=0.01). 6
• Most trials required eGFR ≥30 mL/min/1.73m², though EMPULSE allowed eGFR ≥20. 3

Safety Profile

Monitor for symptomatic hypotension, particularly in patients with renal impairment, elderly patients, those with low systolic blood pressure, or patients on diuretics. 2

• Empagliflozin has minimal blood pressure effects and no excess risk of symptomatic hypotension compared to placebo. 1
• Risk of diabetic ketoacidosis exists, including euglycemic ketoacidosis—assess for signs/symptoms particularly during illness or fasting. 2
• Genital infections (like thrush) occurred more frequently with empagliflozin (2.2%) than placebo (0.7%). 7
• No increased risk of hypoglycemic events compared to placebo in patients with or without diabetes. 6
• Numerically fewer serious adverse events than placebo overall. 1

Quality of Life and Functional Status

• Empagliflozin improves symptoms, physical limitations, and quality of life in patients with heart failure. 1
• Patients were 20-50% more likely to have better NYHA functional class, with significant effects at 12 weeks maintained for at least 2 years. 5
• Modest improvement in quality of life scores at 52 weeks. 3

Post-Myocardial Infarction Population

In the EMPACT-MI trial of 6,522 patients with acute myocardial infarction and left ventricular ejection fraction <45% or signs of congestion, empagliflozin reduced first heart failure hospitalization by 23% (HR 0.77; 95% CI 0.60-0.98; P=0.031) and total heart failure hospitalizations by 33% (rate ratio 0.67; 95% CI 0.51-0.89; P=0.006). 8