Dapagliflozin in Heart Failure with Preserved Ejection Fraction

Clinical Benefits and Recommendations

The American Heart Association recommends dapagliflozin as a first-line treatment for patients with heart failure with preserved ejection fraction (HFpEF), due to its ability to improve clinical outcomes and functional capacity, as demonstrated in the DELIVER trial, which showed a reduction in the combined risk of cardiovascular death or worsening heart failure by 18% (HR 0.82, 95% CI 0.73-0.92, p<0.001) in patients with LVEF >40% 1
Dapagliflozin is the only medication proven to improve both clinical outcomes and functional capacity/quality of life in HFpEF patients, with significant improvements in the Kansas City Cardiomyopathy Questionnaire score and 6-minute walk distance, as demonstrated in the PRESERVED-HF trial, which showed improvements of 5.8 points and 8.2%, respectively, at 12 weeks 1
The European Society of Cardiology recommends SGLT2 inhibitors, including dapagliflozin, as core treatments suitable for all HFpEF patients, based on the positive results of the DELIVER and EMPEROR-PRESERVED trials, which showed reductions in the combined risk of HF hospitalizations or cardiovascular death 2

Dapagliflozin has a strong safety profile, with minimal blood pressure effects, no excess kidney adverse events, and low risk of hypoglycemia, lower limb amputations, bone fracture, or diabetic ketoacidosis, making it ideal for early implementation in patients with HFpEF, as demonstrated in studies with citation 2
The drug provides incremental benefit regardless of background medical therapy, including ACE inhibitors/ARBs, beta-blockers, mineralocorticoid receptor antagonists, and ARNI, with similar hazard ratios in patients with and without diabetes, as demonstrated in the DAPA-HF trial subanalysis 2

Sacubitril/valsartan showed no significant improvement in exercise capacity in HFpEF patients, with a mean difference in 6MWD of 2.5m (p=0.42), whereas dapagliflozin demonstrated significant improvements in functional capacity and quality of life 1
Spironolactone failed to improve exercise capacity in HFpEF trials, despite promising post hoc analyses from the TOPCAT trial, and the FDA issued no final determination on its use for HFpEF, highlighting the need for further research on alternative therapies 1

The American College of Cardiology recommends dapagliflozin 10 mg daily for all patients with heart failure and reduced ejection fraction (HFrEF), reducing cardiovascular death and heart failure hospitalizations by 26% regardless of diabetes status 3, 4
Dapagliflozin provides a 31% reduction in all-cause mortality in patients with HFrEF 5

The American Diabetes Association notes that the benefits of dapagliflozin are completely independent of diabetes status, with a hazard ratio of 0.75 (95% CI 0.63-0.90) for patients with diabetes and 0.73 (95% CI 0.60-0.88) for patients without diabetes 6, 5
Dapagliflozin provides incremental benefit regardless of background medical therapy, including ACE inhibitors/ARBs, beta-blockers, mineralocorticoid receptor antagonists, and angiotensin receptor-neprilysin inhibitors (ARNI) 3

The American College of Cardiology recommends initiating dapagliflozin during hospitalization for heart failure, not deferring to outpatient follow-up, as clinical benefits accrue within days to weeks 3
Dapagliflozin has a strong safety profile with minimal blood pressure effects and no excess kidney adverse events, making it suitable for in-hospital initiation 3

The European Heart Journal recommends initiating dapagliflozin in all patients with HFrEF (LVEF ≤40%) or HFmrEF/HFpEF (LVEF >40%) with NYHA class II-IV symptoms 7, 6
Dapagliflozin should be started at a standard dose of 10 mg once daily, with no titration required and no dose adjustment needed for age, sex, or background therapy 3, 4

Both dapagliflozin and empagliflozin demonstrate robust benefits in HFrEF, with a class effect showing consistent benefits 6, 5
Dapagliflozin has additional evidence in HFpEF (DELIVER trial), making it particularly valuable for preserved ejection fraction 8, 5