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.

2nd Department of Internal Medicine Cardiovascular Medicine General Teaching Hospital and 1st Faculty of Medicine Charles University Prague Czech Republic

5th Department of Internal Medicine Comenius University in Bratislava Slovakia

BHF Cardiovascular Research Centre University of Glasgow UK

Cardiovascular Renal and Metabolism Translational Medicines Unit Early Clinical Development IMED Biotech Unit AstraZeneca Gothenburg Sweden

Clinic of Cardiology National Cardiology Hospital Sofia Bulgaria

Cumming School of Medicine and Libin Cardiovascular Institute University of Calgary AB Canada

Department of Biostatistics and Medical Informatics University of Wisconsin Madison

Department of Cardiology Medanta Gurgaon India

Department of Cardiology Montreal Heart Institute QC Canada

Department of Cardiology University Medical Center and University of Groningen The Netherlands

Department of Cardiology University of Minnesota Minneapolis

Department of Medicine Saarland University Hospital Homburg Saar Germany

Department of Molecular and Clinical Medicine and Cardiology Sahlgrenska Academy Gothenburg Sweden

Department of Myocardial Disease and Heart Failure National Medical Research Center of Cardiology Moscow Russia

Division of Cardiac Surgery St Michael's Hospital University of Toronto ON Canada

Division of Cardiovascular Medicine Brigham and Women's Hospital and Harvard Medical School Boston MA

Late Stage Development Cardiovascular Renal and Metabolism BioPharmaceuticals R and D AstraZeneca Gothenburg Sweden

National University of Cordoba Argentina

Quantitative Clinical Pharmacology IMED Biotech Unit Astra Zeneca Gaithersburg MD

Rigshospitalet Copenhagen University Hospital Denmark

Saint Luke's Mid America Heart Institute University of Missouri Kansas City

Section of Endocrinology Yale University School of Medicine New Haven CT

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Expanding options of supportive care in IgA nephropathy

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ClinicalTrials.gov
NCT03036124