Dapagliflozin for Heart Failure
Yes, dapagliflozin is FDA-approved and strongly recommended for the treatment of heart failure in adults, regardless of diabetes status or ejection fraction. 1
FDA-Approved Indications
Dapagliflozin is specifically indicated to reduce the risk of cardiovascular death, hospitalization for heart failure, and urgent heart failure visits in adults with heart failure. 1 This approval applies to the full spectrum of heart failure patients, making it one of the most broadly applicable heart failure medications available. 2
Evidence Across Heart Failure Types
Heart Failure with Reduced Ejection Fraction (HFrEF)
For patients with HFrEF (ejection fraction ≤40%), dapagliflozin 10 mg daily reduces the composite outcome of worsening heart failure or cardiovascular death by 26% (HR 0.74,95% CI 0.65-0.85). 3, 2 This benefit was demonstrated in the landmark DAPA-HF trial, which enrolled 4,744 patients with NYHA class II-IV symptoms. 3, 4
The benefits break down as follows:
- 30% reduction in first hospitalization for heart failure 2, 5
- 18% reduction in cardiovascular death 2, 5
- 57% reduction in urgent heart failure visits 5
Heart Failure with Preserved Ejection Fraction (HFpEF)
For patients with ejection fraction >40%, dapagliflozin reduces the primary outcome of worsening heart failure or cardiovascular death by 18% (HR 0.82,95% CI 0.73-0.92). 2 The DELIVER trial demonstrated these benefits in 6,263 patients with HFpEF. 2
Benefits Independent of Diabetes Status
A critical feature of dapagliflozin is that its heart failure benefits occur regardless of whether patients have diabetes. 3, 2, 6 In the DAPA-HF trial, 55% of participants did not have diabetes, and the treatment effect was consistent across both groups (P for interaction = 0.80). 4
Among non-diabetic patients specifically:
- Primary outcome reduced by 27% (HR 0.73,95% CI 0.60-0.88) 4
- Benefits maintained even in patients with HbA1c <5.7% (HR 0.67,95% CI 0.47-0.96) 4
Guideline Recommendations
The American College of Cardiology strongly recommends SGLT2 inhibitors for all patients with symptomatic heart failure regardless of ejection fraction or diabetes status. 2 The American Diabetes Association recommends that in patients with type 2 diabetes and established heart failure (with reduced or preserved ejection fraction), an SGLT2 inhibitor with proven benefit should be used to reduce the risk of worsening heart failure, hospitalization, and cardiovascular death. 3
Practical Implementation Advantages
Dapagliflozin has several characteristics that facilitate easy implementation:
- No dose titration required - start at the therapeutic dose of 10 mg daily 3, 2
- No significant effect on blood pressure or heart rate 3, 2
- Benefits occur within weeks of initiation 3
- Effective regardless of background heart failure medications 3, 2
- Can be initiated during hospitalization in stabilized patients 2
Renal Considerations
Dapagliflozin can be used in patients with eGFR as low as 20 mL/min/1.73 m² for heart failure indications. 2, 7 A mild, transient decrease in eGFR may occur after initiation but represents hemodynamic adjustment rather than kidney injury and should not prompt discontinuation. 7 The medication actually provides long-term kidney protection. 3
The FDA label excludes patients with eGFR <30 mL/min/1.73 m² and those on dialysis. 1 In real-world practice, approximately 81% of hospitalized HFrEF patients meet FDA label criteria for dapagliflozin use. 8
Safety Profile
Common adverse events include:
- Volume depletion (approximately 7% of patients) 4
- Genital mycotic infections (1.5-1.7%) 7
- Urinary tract infections (2.3-2.7%) 7
- Hypotension (5.7%) 7
The risk of serious adverse events is numerically lower with dapagliflozin than placebo. 2 Diabetic ketoacidosis risk is significantly lower in non-diabetic populations. 7
Contraindications
Do not use dapagliflozin in patients with:
- History of serious hypersensitivity to dapagliflozin 7, 1
- Polycystic kidney disease 7, 1
- Recent immunosuppressive therapy for kidney disease 7, 1
- Type 1 diabetes (for glycemic control indication) 1
Clinical Bottom Line
Initiate dapagliflozin 10 mg daily in all patients with symptomatic heart failure (NYHA class II-IV) who have an eGFR ≥20-30 mL/min/1.73 m² and no contraindications, regardless of their diabetes status, ejection fraction, or current heart failure medications. 2, 7, 1 The medication should be started early, as deferring initiation is associated with a high likelihood that eligible patients will never receive it within one year. 2