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Dapagliflozin and Diuretic Use in Patients With Heart Failure and Reduced Ejection Fraction in DAPA-HF
Alice M Jackson1, Pooja Dewan1, Inder S Anand2
1BHF Cardiovascular Research Centre, University of Glasgow, UK (A.M.J., P.D., K.F.D., P.S.J., J.J.V.M.).
Insights
Sodium-glucose cotransporter 2 inhibitor dapagliflozin effectively treated heart failure with reduced ejection fraction, regardless of diuretic use. This heart failure medication showed consistent efficacy and safety across all patient subgroups in the DAPA-HF trial.
Area of Science:
- Cardiology
- Pharmacology
- Clinical Trials
Background:
- The DAPA-HF trial investigated dapagliflozin, a sodium-glucose cotransporter 2 inhibitor, for heart failure with reduced ejection fraction (HFrEF).
- Previous findings indicated dapagliflozin reduces risks of worsening heart failure and cardiovascular death in HFrEF patients.
- This analysis specifically examines dapagliflozin's efficacy and tolerability in relation to background diuretic use.
Purpose of the Study:
- To evaluate the efficacy and tolerability of dapagliflozin in patients with HFrEF, stratified by baseline diuretic use.
- To assess whether diuretic therapy influences the benefits of dapagliflozin on cardiovascular outcomes and heart failure events.
- To determine if dapagliflozin's effects on symptoms and treatment toleration vary across different diuretic subgroups.
Main Methods:
- Analysis of subgroups based on baseline diuretic use: no diuretic, and furosemide-equivalent doses <40 mg, 40 mg, and >40 mg daily.
- Evaluation of the primary composite endpoint: cardiovascular death or a worsening heart failure event, including all-cause death and symptom assessment.
- Comparison of dapagliflozin versus placebo across these diuretic subgroups within the DAPA-HF trial.
Main Results:
- Dapagliflozin demonstrated a consistent reduction in the primary endpoint risk across all diuretic subgroups (hazard ratios ranging from 0.57 to 0.78).
- No significant interaction was observed between dapagliflozin's treatment effect and diuretic use (P for interaction=0.61).
- Improvements in heart failure symptoms and treatment tolerability were consistent across subgroups, with no significant changes in diuretic doses post-randomization.
Conclusions:
- The efficacy and safety of dapagliflozin in HFrEF patients are consistent regardless of background diuretic treatment or dose.
- Dapagliflozin provides significant benefits in reducing cardiovascular death or worsening heart failure events across diverse patient populations on diuretic therapy.
- These findings support the use of dapagliflozin as a foundational therapy for HFrEF, irrespective of concomitant diuretic management.
Background:
In the DAPA-HF trial (Dapagliflozin and Prevention of Adverse-Outcomes in Heart Failure), the sodium-glucose cotransporter 2 inhibitor dapagliflozin reduced the risk of worsening heart failure and death in patients with heart failure and reduced ejection fraction. We examined the efficacy and tolerability of dapagliflozin in relation to background diuretic treatment and change in diuretic therapy after randomization to dapagliflozin or placebo.
Methods:
We examined the effects of study treatment in the following subgroups: no diuretic and diuretic dose equivalent to furosemide <40, 40, and >40 mg daily at baseline. We examined the primary composite end point of cardiovascular death or a worsening heart failure event and its components, all-cause death and symptoms.
Results:
Of 4616 analyzable patients, 736 (15.9%) were on no diuretic, 1311 (28.4%) were on <40 mg, 1365 (29.6%) were on 40 mg, and 1204 (26.1%) were taking >40 mg. Compared with placebo, dapagliflozin reduced the risk of the primary end point across each of these subgroups: hazard ratios were 0.57 (95% CI, 0.36-0.92), 0.83 (95% CI, 0.63-1.10), 0.77 (95% CI, 0.60-0.99), and 0.78 (95% CI, 0.63-0.97), respectively (P for interaction=0.61). The hazard ratio in patients taking any diuretic was 0.78 (95% CI, 0.68-0.90). Improvements in symptoms and treatment toleration were consistent across the diuretic subgroups. Diuretic dose did not change in most patients during follow-up, and mean diuretic dose did not differ between the dapagliflozin and placebo groups after randomization.
Conclusions:
The efficacy and safety of dapagliflozin were consistent across the diuretic subgroups examined in DAPA-HF. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03036124.
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