What is the recommended dose of dapagliflozin (SGLT2 inhibitor) for patients with Heart Failure with Reduced Ejection Fraction (HFrEF)?

Dapagliflozin Dosing in Heart Failure with Reduced Ejection Fraction (HFrEF)

The recommended dose of dapagliflozin for patients with Heart Failure with Reduced Ejection Fraction (HFrEF) is 10 mg orally once daily, regardless of diabetes status. 1

Dosing Guidelines

• Dapagliflozin 10 mg once daily is the standard dose for reducing the risk of cardiovascular death, hospitalization for heart failure, and urgent heart failure visits in adults with HFrEF 1
• The 10 mg daily dose has been consistently used in clinical trials demonstrating cardiovascular benefits in HFrEF patients 1, 2
• No dose adjustment is needed based on diabetes status, as the benefits of dapagliflozin in HFrEF are consistent regardless of whether patients have diabetes or not 2
• Dapagliflozin can be initiated in patients with eGFR ≥25 mL/min/1.73 m² 1, 3
• If eGFR falls below 25 mL/min/1.73 m² while on treatment, dapagliflozin 10 mg can be continued for cardiovascular benefit until dialysis 3, 1

Renal Considerations

• Initiation of dapagliflozin is not recommended in patients with eGFR <25 mL/min/1.73 m² 1, 3
• For patients already on dapagliflozin whose eGFR drops below 25 mL/min/1.73 m², the medication can be continued at 10 mg daily for heart failure benefits 1, 3
• Assess renal function prior to initiation and periodically during treatment 1
• While glucose-lowering efficacy decreases with declining eGFR, cardiovascular benefits are preserved even at lower eGFR levels 3

Efficacy in HFrEF

• In the DAPA-HF trial, dapagliflozin 10 mg daily reduced the composite risk of worsening heart failure or cardiovascular death by 26% (HR 0.74 [95% CI 0.65-0.85]) compared to placebo 1, 2
• The benefits of dapagliflozin were consistent across subgroups, including patients with or without diabetes 2
• Dapagliflozin reduced hospitalization for heart failure by 30% (HR 0.70 [95% CI 0.59-0.83]) 1
• Cardiovascular death was reduced by 18% (HR 0.82 [95% CI 0.69-0.98]) 1

Combination Therapy Considerations

• Dapagliflozin 10 mg daily can be safely combined with other heart failure medications including ACE inhibitors, ARBs, ARNIs, beta-blockers, and mineralocorticoid receptor antagonists 1, 4
• The efficacy and safety of dapagliflozin are similar in patients taking or not taking mineralocorticoid receptor antagonists, supporting the use of both drugs together 4
• Dapagliflozin should be added to standard guideline-directed medical therapy for HFrEF 1, 3

Temporary Interruption Considerations

• Hold dapagliflozin in patients with hemodynamic instability (systolic BP <100 mmHg) or requiring intravenous vasopressors/inotropes 5
• Withhold dapagliflozin for at least 3 days before major surgery or procedures associated with prolonged fasting 1
• Resume dapagliflozin when the patient is clinically stable and has resumed oral intake 1
• If temporarily held during acute hemodynamic instability, restart once the patient is stabilized 5

Common Pitfalls to Avoid

• Unnecessarily holding dapagliflozin during hospitalization may lead to missed therapeutic benefits 5
• Failure to continue dapagliflozin in patients with declining renal function who may still benefit from its cardiovascular effects 3, 1
• Not recognizing that the cardiovascular benefits of dapagliflozin in HFrEF are independent of its glucose-lowering effects 2
• Overlooking the need to assess volume status before initiating dapagliflozin, as volume depletion should be corrected first 1

In summary, dapagliflozin 10 mg once daily is the recommended dose for HFrEF patients, with proven benefits in reducing heart failure hospitalizations and cardiovascular death regardless of diabetes status. The medication can be initiated in patients with eGFR ≥25 mL/min/1.73 m² and continued even if renal function declines, as long as the patient is not on dialysis.