What is the role of Farxiga (dapagliflozin) in managing heart failure?

Farxiga (Dapagliflozin) in Heart Failure Management

Dapagliflozin 10 mg daily should be initiated in all patients with symptomatic heart failure regardless of ejection fraction or diabetes status, as it reduces cardiovascular death, heart failure hospitalizations, and improves quality of life. 1, 2

Evidence Across the Heart Failure Spectrum

Heart Failure with Reduced Ejection Fraction (HFrEF)

• In the DAPA-HF trial of 4,744 patients with HFrEF (LVEF ≤40%), dapagliflozin reduced the composite outcome of cardiovascular death or worsening heart failure by 26% (HR 0.74,95% CI 0.65-0.85) compared to placebo. 1
• The benefit was consistent regardless of diabetes status—45% of patients had type 2 diabetes, yet outcomes improved equally in both diabetic and non-diabetic patients. 3, 4
• Clinical benefit emerges rapidly, with statistically significant risk reduction apparent by 28 days after initiation (HR 0.51,95% CI 0.28-0.94). 5

Heart Failure with Preserved Ejection Fraction (HFpEF)

• The DELIVER trial enrolled 6,263 patients with LVEF >40% and demonstrated that dapagliflozin reduced worsening heart failure or cardiovascular death by 18% (HR 0.82,95% CI 0.73-0.92). 1, 6
• Benefits were similar in patients with LVEF ≥60% and those with LVEF <60%, establishing efficacy across the entire preserved ejection fraction spectrum. 6

Timing of Initiation: The Hospital Opportunity

Dapagliflozin should be initiated during heart failure hospitalization in stabilized patients, not deferred to outpatient follow-up. 7

• Patients recently hospitalized for heart failure derive the greatest absolute benefit—those hospitalized within 12 months had a 9.9% absolute risk reduction at 2 years compared to 2.1% in those never hospitalized. 5
• Deferring in-hospital initiation is associated with >75% likelihood that eligible patients will never receive the medication within 1 year. 7
• The drug has minimal blood pressure effects, no excess risk of symptomatic hypotension, and numerically fewer serious adverse events than placebo, making it well-suited for the hospitalized population. 7

Benefits Independent of Background Therapy

• Dapagliflozin provides incremental benefit regardless of whether patients are on optimal guideline-directed medical therapy (GDMT). 7
• In patients already on ACE inhibitor/ARB, beta-blocker, and mineralocorticoid receptor antagonist, dapagliflozin still reduced the primary outcome by 26% (HR 0.74,95% CI 0.59-0.93). 7
• The drug works independently of glucose-lowering effects, representing direct cardiovascular benefit through mechanisms beyond glycemic control. 1, 2

Symptom and Quality of Life Improvements

• Patients treated with dapagliflozin experienced clinically meaningful improvements in Kansas City Cardiomyopathy Questionnaire (KCCQ) scores—mean improvements of 2.8 points in total symptom score, 2.5 points in clinical summary score, and 2.3 points in overall summary score at 8 months (P<0.0001 for all). 8
• The number needed to treat for at least moderate improvement in health status was only 15 patients. 8
• Fewer patients experienced deterioration in symptoms (OR 0.84,95% CI 0.78-0.90), and more patients had small, moderate, and large improvements in quality of life. 8

Diuretic Interactions and Dosing

• Dapagliflozin efficacy is consistent across all diuretic doses, including patients on no diuretic (HR 0.57), <40 mg furosemide equivalent (HR 0.83), 40 mg (HR 0.77), and >40 mg (HR 0.78). 9
• Mean diuretic doses did not differ between dapagliflozin and placebo groups after randomization, indicating dapagliflozin does not necessitate routine diuretic dose adjustments. 9
• The drug's mechanism as an SGLT2 inhibitor provides natriuresis without the adverse metabolic effects of traditional loop diuretics. 9

Renal Benefits in Heart Failure Patients

• In the DAPA-CKD trial, dapagliflozin reduced the composite of ≥50% sustained eGFR decline, progression to end-stage kidney disease, or cardiovascular/renal death by 39% (HR 0.61,95% CI 0.51-0.72). 3
• The drug preserves kidney function rather than causing adverse renal effects, with benefits observed even in patients with eGFR as low as 25 mL/min/1.73 m². 7, 3
• Dapagliflozin reduced hospitalization for heart failure by 49% (HR 0.51,95% CI 0.34-0.76) in the chronic kidney disease population. 3

Safety Considerations and Monitoring

Key safety monitoring includes:

• Ketoacidosis risk: Monitor for symptoms (nausea, vomiting, abdominal pain, dyspnea) even when blood glucose <250 mg/dL, particularly in patients who are acutely ill, fasting, or on ketogenic diets. 3
• Volume depletion: Higher risk in patients on diuretics, age ≥65 years, low baseline blood pressure, or renal impairment—counsel patients to maintain adequate fluid intake and report reduced oral intake. 3
• Genital mycotic infections: Women may develop vaginal yeast infections; men may develop balanitis—most respond to over-the-counter antifungals. 3

Contraindications:

• Allergy to dapagliflozin (may manifest as rash, hives, or angioedema). 3
• Polycystic kidney disease or patients on immunosuppressive therapy for kidney disease (drug not expected to work in these conditions). 3

Practical Implementation Algorithm

1. Identify eligible patients: All symptomatic heart failure patients (NYHA class II-IV) regardless of ejection fraction or diabetes status. 1, 2

2. Initiate during hospitalization if applicable: Start dapagliflozin 10 mg daily in stabilized hospitalized patients before discharge to maximize adherence and early benefit. 7

3. No dose titration required: Fixed dose of 10 mg once daily—no need for gradual up-titration unlike beta-blockers or ARNI. 3, 4

4. Continue existing GDMT: Do not discontinue or reduce ACE inhibitors, ARBs, beta-blockers, or MRAs—dapagliflozin provides additive benefit. 7

5. Monitor within first month: Assess for volume status, ketoacidosis symptoms, and genital infections, but expect minimal adverse effects. 3