When is Jardiance (Empboardi) indicated for patients with Heart Failure with Reduced Ejection Fraction (HFrEF)?

From the Guidelines

Jardiance (empagliflozin) is indicated for patients with Heart Failure with Reduced Ejection Fraction (HFrEF) to reduce the risk of HF hospitalization and death, as recommended by the 2024 ESC guidelines for the management of chronic coronary syndromes 1.

Key Points

• The recommendation is based on the highest quality and most recent evidence, which prioritizes morbidity, mortality, and quality of life as outcomes.
• An SGLT2 inhibitor, such as empagliflozin, is recommended for CCS patients with HFrEF, in addition to an ACE-I, an MRA, and a beta-blocker, to reduce the risk of HF hospitalization and death 1.
• The benefits of empagliflozin in patients with HFrEF are supported by studies such as EMPEROR-Preserved, which showed a significant reduction in the primary composite endpoint of time to HF hospitalization or cardiovascular death 1.
• Patients with HFrEF should have adequate renal function, typically an eGFR of at least 20 mL/min/1.73m², as the efficacy of empagliflozin decreases with declining kidney function.
• Common side effects of empagliflozin include genital mycotic infections and urinary tract infections, so patients should be monitored for these conditions.

Clinical Considerations

• Before starting Jardiance, patients should be assessed for volume status and renal function, and any volume depletion should be corrected.
• The standard dosage of Jardiance is 10 mg once daily, taken orally with or without food.
• Empagliflozin works as a sodium-glucose cotransporter-2 (SGLT2) inhibitor, which promotes glucose excretion in urine but also has beneficial cardiovascular effects, including reduced cardiac preload and afterload, improved ventricular loading conditions, and reduced myocardial oxygen demand, all of which contribute to its benefits in heart failure management.
• The 2022 AHA/ACC/HFSA guideline for the management of heart failure also supports the use of SGLT2 inhibitors, such as empagliflozin, in patients with HFrEF, with a Class IIa recommendation for patients with symptomatic HFmrEF 1.

From the FDA Drug Label

The efficacy and safety of dapagliflozin 10 mg were assessed independently in two Phase 3 trials in adult patients with heart failure Dapagliflozin And Prevention of Adverse outcomes in Heart Failure (DAPA-HF, NCT03036124) was an international, multicenter, randomized, double-blind, placebo-controlled trial in patients with heart failure [New York Heart Association (NYHA) functional class II-IV] with reduced ejection fraction [left ventricular ejection fraction (LVEF) 40% or less] to determine whether dapagliflozin reduces the risk of cardiovascular death and hospitalization for heart failure.

In DAPA-HF, at baseline, 94% of patients were treated with ACEi, ARB or angiotensin receptor-neprilysin inhibitor (ARNI, including sacubitril/valsartan 11%), 96% with beta-blocker, 71% with mineralocorticoid receptor antagonist (MRA), 93% with diuretic, and 26% had an implantable device (with defibrillator function)

Table 17: Treatment Effect for the Primary Composite Endpointand, its Components in the DAPA-HF and DELIVER Trials DAPA-HF Trial Patients with events(event rate) Hazard ratio(95% CI) p-value† Efficacy Variable (Time to first occurrence) Dapagliflozin 10 mgN=2373 PlaceboN=2371 Composite of Hospitalization for Heart Failure, CV Death‡ or Urgent Heart Failure Visit 386(11.6) 502(15.6) 0.74(0.65,0. 85) <0.0001

Jardiance (Empagliflozin) is not indicated for patients with Heart Failure with Reduced Ejection Fraction (HFrEF) according to the provided label, as the label is for dapagliflozin, a different medication. However, based on the information provided for dapagliflozin, it is indicated for patients with HFrEF as shown in the DAPA-HF trial. The trial demonstrated that dapagliflozin reduced the incidence of the primary composite endpoint of CV death, hospitalization for heart failure or urgent heart failure visit in patients with HFrEF 2. Key points:

• Dapagliflozin is indicated for patients with HFrEF.
• The DAPA-HF trial showed a reduction in the primary composite endpoint.
• The medication in question is actually dapagliflozin, not Jardiance (Empagliflozin).

From the Research

Indications for Jardiance (Empboardi) in Heart Failure with Reduced Ejection Fraction (HFrEF)

• Jardiance (Empboardi) is indicated for patients with Heart Failure with Reduced Ejection Fraction (HFrEF) as it has been shown to reduce the risk of cardiovascular death or hospitalization for heart failure 3, 4, 5, 6.
• The beneficial effects of empagliflozin on cardiovascular death or hospitalization for heart failure are seen irrespective of the presence or absence of type 2 diabetes and regardless of background heart failure therapies 3, 4.
• Studies have demonstrated that empagliflozin reduces the combined risk of death, hospitalization for heart failure, or an emergent/urgent heart failure visit requiring intravenous treatment in patients with HFrEF 4, 5.

Patient Population

• Jardiance (Empboardi) is approved for the treatment of all adults with symptomatic chronic heart failure, regardless of their left ventricular ejection fraction (LVEF) 3.
• The EMPEROR-Reduced trial demonstrated the benefits of empagliflozin in patients with class II to IV heart failure with an ejection fraction of ≤40% 4.
• A post hoc analysis of the EMPEROR-Reduced trial showed that empagliflozin offers cardiovascular and renal benefits in patients with heart failure with reduced ejection fraction regardless of the cause of heart failure (ischemic or nonischemic) 6.

Clinical Benefits

• Empagliflozin has been shown to improve health-related quality of life (HRQOL) and is generally well tolerated, with an adverse event profile that is generally consistent with that seen in patients with type 2 diabetes 3.
• The treatment reduces the total number of heart failure hospitalizations that require intensive care and the total number of all hospitalizations that require a vasopressor or positive inotropic drug 4, 7.
• Empaglifloxin also reduces the risk of the composite renal endpoint and improves renal outcomes in patients with HFrEF 5.