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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.).
Circulation
|July 17, 2020
Summary
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.
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