What types of chronic heart failure (by left‑ventricular ejection fraction, e.g., heart failure with reduced ejection fraction and heart failure with mildly reduced ejection fraction) is Farxiga (dapagliflozin) approved for?

Farxiga (Dapagliflozin) Indications for Heart Failure

Farxiga is approved for heart failure with reduced ejection fraction (HFrEF, LVEF ≤40%), heart failure with mildly reduced ejection fraction (HFmrEF, LVEF 41-49%), and heart failure with preserved ejection fraction (HFpEF, LVEF ≥50%). 1

FDA-Approved Indications

The FDA label for dapagliflozin encompasses a broad spectrum of heart failure based on ejection fraction:

• HFrEF (LVEF ≤40%): Approved to reduce the risk of cardiovascular death, hospitalization for heart failure, and urgent heart failure visits 1
• HFmrEF and HFpEF (LVEF >40%): Approved based on the DELIVER trial, which included patients with LVEF >40% 1, 2

Guideline Recommendations by Heart Failure Type

Heart Failure with Reduced Ejection Fraction (LVEF <40%)

SGLT2 inhibitors including dapagliflozin receive a Class I (strongest) recommendation from the 2024 ESC guidelines for patients with HFrEF. 3 The 2022 AHA/ACC/HFSA guidelines provide intermediate economic value designation for SGLT2 inhibitors in symptomatic chronic HFrEF 3

• Dapagliflozin 10 mg once daily reduces the composite endpoint of cardiovascular death or hospitalization for heart failure by 26% (HR 0.74,95% CI 0.65-0.85) 1
• Benefits are consistent regardless of diabetes status 4, 5
• Should be added to guideline-directed medical therapy including ACE inhibitors/ARBs/ARNIs, beta-blockers, and mineralocorticoid receptor antagonists 3

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

SGLT2 inhibitors receive a Class I recommendation from the 2024 ESC guidelines and Class 2a recommendation from the 2022 AHA/ACC/HFSA guidelines for HFmrEF. 3

• Dapagliflozin reduces the risk of cardiovascular death or heart failure hospitalization by 18% in this population (HR 0.82,95% CI 0.73-0.92) 1, 2
• The 2022 AHA/ACC/HFSA guidelines note that patients with LVEF on the lower end of the HFmrEF spectrum (closer to 40%) respond similarly to HFrEF patients 3
• Other guideline-directed medical therapies (ACE inhibitors, ARBs, ARNIs, beta-blockers, MRAs) receive Class 2b recommendations for HFmrEF 3

Heart Failure with Preserved Ejection Fraction (LVEF ≥50%)

SGLT2 inhibitors receive a Class I recommendation from the 2024 ESC guidelines and Class 2a recommendation from the 2022 AHA/ACC/HFSA guidelines for HFpEF. 3

• The DELIVER trial demonstrated an 18% reduction in the composite endpoint of cardiovascular death, hospitalization for heart failure, or urgent heart failure visits (HR 0.82,95% CI 0.73-0.92) 1, 2
• Benefits were consistent across the entire LVEF spectrum in DELIVER, including patients with LVEF ≥60% 2
• SGLT2 inhibitors are the only Class I or 2a recommendation for HFpEF with robust mortality/morbidity data 3

Heart Failure with Improved Ejection Fraction (HFimpEF)

Patients with previously reduced ejection fraction that has improved to >40% should continue HFrEF treatment, including dapagliflozin. 3

• The 2022 AHA/ACC/HFSA guidelines emphasize that guideline-directed medical therapy should be continued even when LVEF improves to prevent relapse 3
• Discontinuation of therapy can lead to recurrent left ventricular dysfunction 3

Key Exclusion Criteria from FDA Label

The following patients were excluded from pivotal trials and should be prescribed dapagliflozin with caution:

• eGFR <30 mL/min/1.73 m² or on dialysis (this was the most common reason for ineligibility in real-world cohorts, affecting 18.5-20% of HFrEF patients) 1, 6, 7
• Type 1 diabetes mellitus 1, 6
• Systolic blood pressure <95 mmHg (affected 6.5-8.4% of real-world HFrEF patients) 6, 7

Practical Implementation

Start dapagliflozin 10 mg once daily, which is the dose used in all major heart failure trials. 8, 1

• Can be initiated safely in both acute (during hospitalization) and chronic care settings 1
• Add to existing guideline-directed medical therapy rather than using as monotherapy 8
• Approximately 81% of real-world HFrEF patients in the GWTG-HF registry would be eligible for dapagliflozin according to FDA label criteria 6
• Benefits extend beyond heart failure outcomes, including a 50% reduction in composite renal outcomes and decreased eGFR decline 8, 1