How does Jardiance (empagliflozin) help patients with heart failure, particularly those with reduced ejection fraction?

How Jardiance (Empagliflozin) Helps Heart Failure

Jardiance reduces heart failure hospitalizations by 25-35% and cardiovascular death by 18-21% across the entire spectrum of heart failure, regardless of ejection fraction or diabetes status, making it a cornerstone therapy that should be initiated in all symptomatic heart failure patients. 1, 2, 3

Mechanisms and Clinical Benefits

Jardiance works through multiple complementary mechanisms beyond its glucose-lowering effects:

Primary Cardiovascular Effects

• Reduces heart failure hospitalizations by 29-35% in patients with reduced ejection fraction (LVEF ≤40%), with benefits appearing as early as 12 days after initiation 1, 3, 4
• Decreases cardiovascular death by 18% in heart failure with reduced ejection fraction, though this benefit is driven more by preventing hospitalizations than mortality 1, 5
• Lowers the combined risk of cardiovascular death or heart failure hospitalization by 21% in patients with preserved ejection fraction (LVEF >40%), with the benefit primarily from reducing hospitalizations 1, 6

Rapid and Sustained Clinical Improvements

• Benefits emerge within 12 days of starting treatment, with a 58% relative risk reduction observed at this early timepoint 2, 3
• Reduces total heart failure hospitalizations (not just first events), including those requiring intensive care by 33% and those requiring vasopressors or mechanical support by 36% 4
• Decreases emergent/urgent heart failure visits requiring intravenous treatment by 24% 4
• Improves New York Heart Association functional class by 20-40%, with patients more likely to improve and less likely to worsen, starting at 28 days and maintained long-term 4

Renal Protection

• Slows the decline in kidney function across all stages of renal disease, reducing the slope of eGFR decline significantly 1, 3
• Reduces serious kidney complications by 48% in patients with heart failure and reduced ejection fraction 7
• Can be initiated with eGFR as low as 20-30 mL/min/1.73m² and continued even if eGFR falls below 25 mL/min/1.73m² while on treatment 2, 8

Universal Applicability Across Heart Failure Spectrum

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

• Class I, Level A recommendation from the American College of Cardiology and American Heart Association for all symptomatic patients 2, 3
• Empagliflozin 10 mg daily reduces the composite outcome of cardiovascular death or heart failure hospitalization by 25% (HR 0.75,95% CI 0.65-0.86) 2, 9

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

• Class 2a, Level B-R recommendation to decrease heart failure hospitalizations and cardiovascular mortality 1, 3
• Subgroup analysis from EMPEROR-Preserved showed consistent benefit in 1,983 patients with LVEF 41-49%, with no significant interaction by ejection fraction subgroups 1, 3
• Patients with LVEF on the lower end of this spectrum respond similarly to HFrEF patients and should be treated with the same guideline-directed medical therapy 1, 3

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

• Class 2a, Level B-R recommendation for symptomatic patients to decrease heart failure hospitalizations 1, 2
• 21% reduction in cardiovascular death or heart failure hospitalization (HR 0.79,95% CI 0.69-0.90) in the EMPEROR-Preserved trial 1, 6
• Benefits maintained across the entire LVEF spectrum, though some signal for lower benefit at LVEF >62.5% 1

Independence from Diabetes Status

• Equally effective in patients with and without diabetes, with no significant interaction by baseline diabetes status (P-interaction=0.57) 5
• Works across the continuum of HbA1c levels, from normoglycemia (HbA1c <5.7%) through prediabetes to diabetes 5
• Does not lower HbA1c in non-diabetic patients and does not increase hypoglycemia risk in those without diabetes 5
• 50% of patients in EMPEROR-Reduced had diabetes, 34% had prediabetes, and 16% had normoglycemia, with consistent benefits across all groups 5

Unique Practical Advantages

Ease of Implementation

• No dose titration required—start and stay at empagliflozin 10 mg once daily 2, 3, 8
• No significant effect on blood pressure, heart rate, or potassium levels, making it safe to combine with other guideline-directed medical therapies 2, 8
• Can be initiated during hospitalization in stabilized patients (no increase in IV diuretics for 6 hours, no IV vasodilators or inotropes for 24 hours) 2, 3

Facilitates Other Therapies

• Patients on SGLT2 inhibitors are less likely to discontinue mineralocorticoid receptor antagonists or experience severe hyperkalemia 8
• Benefits are independent of background medical therapy, including whether patients received ≥50% of target doses of other heart failure medications 8

Safety Profile and Monitoring

Common Adverse Effects

• Genital mycotic infections occur in 1.5-1.7% of patients, compared to 0.6% with placebo 2, 7
• Urinary tract infections in 2.3-2.7% of patients 2
• Symptomatic hypotension in approximately 5.7%, particularly in volume-depleted patients, elderly, those with low systolic blood pressure, or on diuretics 2, 3

Critical Monitoring Points

• Monitor for signs of volume depletion (hypotension, dizziness), especially at initiation 2, 3
• Assess for ketoacidosis symptoms (including euglycemic ketoacidosis), particularly during illness or fasting 3
• Do not discontinue for mild eGFR decline—a transient drop after initiation is expected and provides long-term kidney protection 2
• Monitor renal function periodically, but recognize that cardiovascular benefits are preserved even at lower eGFR levels 8

Clinical Implementation Algorithm

1. Identify all symptomatic heart failure patients (NYHA class II-IV) regardless of ejection fraction 2, 3
2. Assess contraindications: eGFR <20 mL/min/1.73m² (though can continue if already on treatment), history of serious hypersensitivity to empagliflozin 2, 3
3. Initiate empagliflozin 10 mg once daily without dose titration 2, 3, 8
4. Start early—during hospitalization if stabilized, or immediately in outpatient setting, as deferring initiation results in many eligible patients never receiving the medication within 1 year 2
5. Continue indefinitely unless contraindications develop, even if eGFR declines below 25 mL/min/1.73m² 2, 8

Quality of Life Improvements

• Modest but significant improvements in quality of life scores at 52 weeks 1, 3
• Reduces the need for diuretic intensification by 33% compared to placebo (297 vs 414 patients, HR 0.67,95% CI 0.56-0.78) 4
• Overall risk of any inpatient or outpatient worsening heart failure event was 48.1 per 100 patient-years with placebo, reduced by 30% with empagliflozin (HR 0.70,95% CI 0.63-0.78) 4