Cardiac Indication for Farxiga (Dapagliflozin) in Heart Failure with Reduced Ejection Fraction
Farxiga (dapagliflozin) is indicated for the treatment of heart failure with reduced ejection fraction (HFrEF) to reduce the risk of cardiovascular death and hospitalization for heart failure, regardless of diabetes status. 1
Efficacy in Heart Failure with Reduced Ejection Fraction
Dapagliflozin's approval for HFrEF is based on robust clinical evidence from the DAPA-HF trial, which demonstrated:
- 26% reduction in the risk of worsening heart failure or cardiovascular death (HR 0.74 [95% CI 0.65-0.85]; p<0.0001) 1
- 30% reduction in hospitalizations for heart failure (HR 0.70 [95% CI 0.59-0.83]) 1
- 18% reduction in cardiovascular death (HR 0.82 [95% CI 0.69-0.98]) 1
These benefits were consistent regardless of:
- Presence or absence of type 2 diabetes 2
- Background heart failure therapies 2
- Age, sex, and other demographic factors 1
Dosage and Administration
- The recommended dose is 10 mg once daily 3, 1
- Can be initiated during hospitalization for heart failure after patient stabilization 3
- Can be used in patients with eGFR ≥20 mL/min/1.73m² (dapagliflozin is the only SGLT2 inhibitor approved for use down to this eGFR level) 3
- Should be continued indefinitely as part of comprehensive heart failure management 3
Mechanism of Action in Heart Failure
Dapagliflozin provides cardiovascular benefits through multiple mechanisms:
- Reduction in preload and afterload
- Decreased myocardial oxygen demand
- Improved cardiac metabolism
- Reduced cardiac fibrosis
- Natriuretic and diuretic effects without activating the sympathetic nervous system 3
Place in Heart Failure Treatment Algorithm
Dapagliflozin should be considered a first-line therapy for heart failure with reduced ejection fraction, alongside:
- ACE inhibitors, ARBs, or ARNI
- Evidence-based beta blockers
- Mineralocorticoid receptor antagonists (MRAs)
- Diuretics for symptom management 3
Additional Benefits in Heart Failure Management
- Reduces the need for loop diuretic initiation by 32% 4
- Attenuates the increase in loop diuretic doses over time (treatment effect of -2.5 mg/year compared to placebo) 4
- Reduces total heart failure events (first and recurrent), not just first events 5
Safety Considerations
Dapagliflozin is generally well-tolerated with a safety profile consistent with other SGLT2 inhibitors. Key monitoring needs include:
- Genital mycotic infections
- Urinary tract infections
- Volume depletion/hypotension
- Rare risk of euglycemic diabetic ketoacidosis 3
The safety profile remains consistent even when initiated during or shortly after hospitalization for heart failure 6.
Expanded Indications
While this question focuses on HFrEF, it's worth noting that dapagliflozin has also shown benefit in heart failure with mildly reduced or preserved ejection fraction (HFpEF) based on the DELIVER trial, which demonstrated an 18% reduction in the primary composite outcome of worsening heart failure or cardiovascular death (HR 0.82 [95% CI 0.73-0.92]; p=0.0008) 1, 7.