Dapagliflozin for Heart Failure with LVEF 40-45%
Yes, dapagliflozin is appropriate and strongly recommended for this patient with heart failure and LVEF 40-45%, as this ejection fraction falls within the heart failure with mildly reduced ejection fraction (HFmrEF) category where SGLT2 inhibitors have demonstrated significant mortality and morbidity benefits.
Evidence Supporting Use in This LVEF Range
Trial Data Specific to LVEF 40-45%
The DELIVER trial specifically enrolled patients with LVEF >40% and demonstrated a 21% reduction in the composite endpoint of cardiovascular death or heart failure hospitalization in the subgroup of 1,983 patients with LVEF 41-49%, which directly includes your patient's ejection fraction range 1.
The FDA label for dapagliflozin explicitly includes patients with LVEF >40%, and the DELIVER trial showed consistent benefit across the full spectrum of ejection fractions studied, with the primary composite endpoint (hospitalization for heart failure, cardiovascular death, or urgent heart failure visit) reduced by 18% (HR 0.82,95% CI 0.73-0.92, p=0.0008) 2.
Guideline Recommendations
The 2023 American College of Cardiology expert consensus specifically recommends SGLT2 inhibitors as guideline-directed medical therapy for heart failure with preserved ejection fraction (HFpEF), which encompasses patients with LVEF >40% 3.
Empagliflozin (the other major SGLT2 inhibitor in this class) receives a Class 2a recommendation for patients with HFmrEF, and the evidence for dapagliflozin is equally strong in this population 1.
Clinical Benefits in This Population
Mortality and Morbidity Outcomes
Dapagliflozin reduced the risk of worsening heart failure events (hospitalization or urgent visits) by 21% (HR 0.79,95% CI 0.69-0.91) in the DELIVER trial population 2.
Cardiovascular death showed a favorable trend (HR 0.88,95% CI 0.74-1.05), and the treatment effect was consistent regardless of diabetes status 2.
Quality of Life and Symptom Burden
In pooled analysis of DAPA-HF and DELIVER trials, dapagliflozin improved Kansas City Cardiomyopathy Questionnaire scores consistently across the full LVEF spectrum, with benefits evident in patients with LVEF 41-60% 4.
Fewer patients on dapagliflozin experienced clinically meaningful deteriorations in health status (21% vs 26% in the LVEF 41-60% group), and more experienced meaningful improvements (51% vs 49%) 4.
The number needed to treat to achieve a ≥5 point improvement in health status was 20 across the LVEF spectrum 4.
Practical Implementation
Dosing and Initiation
Start dapagliflozin 10 mg once daily, which is the standard dose used in all major heart failure trials 1, 2.
Add dapagliflozin to existing guideline-directed medical therapy rather than using as monotherapy 1.
Dapagliflozin can be initiated safely in both acute and chronic care settings 3.
Monitoring Requirements
Check baseline renal function before initiation; dapagliflozin is contraindicated in patients on dialysis 1.
Monitor renal function regularly after initiation, particularly in patients with baseline kidney disease 1.
Assess volume status regularly due to the diuretic effects of SGLT2 inhibitors 1.
Safety Profile
The incidence of adverse events was similar between dapagliflozin and placebo groups in the DELIVER trial 2, 5.
Serious adverse events did not occur more frequently with dapagliflozin regardless of baseline characteristics 6.
Special Considerations
Comprehensive Heart Failure Management
While dapagliflozin is appropriate, ensure the patient is also on other guideline-directed medical therapy as indicated, including beta-blockers (for LVEF <50%), ACE inhibitors/ARBs (for LVEF <50%), and mineralocorticoid receptor antagonists if symptomatic 7.
The 2023 ACC guidelines emphasize that management should also address comorbidities including hypertension, diabetes, obesity, atrial fibrillation, coronary artery disease, chronic kidney disease, and obstructive sleep apnea 3.
Renal Protection
- Beyond heart failure benefits, dapagliflozin decreased the slope of eGFR decline and reduced the risk of composite renal outcomes by 50% in the EMPA-REG OUTCOME trial, providing additional long-term benefit 1.