What is the recommended dosing of Farxiga (dapagliflozin) in patients with diastolic congestive heart failure (CHF)?

Dosing of Dapagliflozin (Farxiga) in Diastolic Heart Failure

The recommended dosage of dapagliflozin for patients with diastolic heart failure is 10 mg orally once daily, regardless of ejection fraction or diabetes status. 1, 2

Dosing Guidelines

• Dapagliflozin 10 mg once daily is the standard dose for heart failure treatment, with no need for dose titration or adjustment based on heart failure symptoms 1, 3
• The same 10 mg daily dose is effective across the spectrum of heart failure, including heart failure with preserved ejection fraction (HFpEF) or diastolic heart failure 2, 4
• Unlike many other heart failure medications, dapagliflozin does not require dose titration or up-titration, making it easier to implement in clinical practice 5
• The 10 mg dose was consistently used in all major clinical trials demonstrating benefit in heart failure patients, including DAPA-HF and DELIVER trials 6, 4

Renal Considerations

• Dapagliflozin can be initiated in patients with eGFR ≥25 mL/min/1.73 m² 3, 1
• Initiation is not recommended in patients with eGFR <25 mL/min/1.73 m² 1
• 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
• While glucose-lowering efficacy decreases with declining renal function, cardiovascular benefits are preserved even at lower eGFR levels 3

Clinical Evidence in Diastolic Heart Failure

• The DELIVER trial demonstrated that dapagliflozin 10 mg daily reduced the composite outcome of worsening heart failure or cardiovascular death by 18% in patients with heart failure and ejection fraction >40% (HR 0.82 [95% CI 0.73-0.92]; P<0.001) 2, 4
• Benefits were consistent regardless of left ventricular ejection fraction, including patients with ejection fraction ≥60% 4
• Dapagliflozin's effectiveness was similar regardless of whether patients received ≥50% of the target doses of background heart failure medications 5
• Benefits occur within weeks after drug initiation and are independent of age, sex, or background medical therapy 5, 6

Practical Administration Considerations

• Dapagliflozin can be taken at any time of day without regard to meals 1
• Temporarily withhold dapagliflozin for at least 3 days prior to major surgery or procedures associated with prolonged fasting 1
• Resume dapagliflozin when the patient is clinically stable and has resumed oral intake 1
• Hold dapagliflozin in patients with hemodynamic instability or requiring intravenous vasopressors/inotropes, and restart once the patient is stabilized 3

Integration with Other Heart Failure Therapies

• Dapagliflozin should be added to standard guideline-directed medical therapy for heart failure 3, 2
• SGLT2 inhibitors like dapagliflozin are unique among heart failure medications as they do not affect blood pressure, heart rate, or potassium levels, making them easier to combine with other heart failure medications 5
• Dapagliflozin appears to facilitate the use of mineralocorticoid receptor antagonists (MRAs), as patients on SGLT2 inhibitors are less likely to discontinue MRAs or experience severe hyperkalemia 5

Safety Considerations

• The most common adverse effects include genital mycotic infections and volume depletion 6
• Assess volume status before initiating dapagliflozin and correct volume depletion if present 1
• Monitor for signs of diabetic ketoacidosis, particularly in patients with type 1 diabetes (for whom dapagliflozin is not indicated) 1
• The frequency of adverse events related to volume depletion, renal dysfunction, and hypoglycemia in heart failure patients is similar to placebo 6

By following these dosing recommendations, clinicians can effectively incorporate dapagliflozin into the treatment regimen for patients with diastolic heart failure, potentially reducing hospitalizations and improving outcomes.