Effect of Dapagliflozin on Worsening Heart Failure and Cardiovascular Death in Patients With Heart Failure With and Without Diabetes
Language English Country United States Media print
Document type Clinical Trial, Phase III, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't
Grant support
P30 DK045735
NIDDK NIH HHS - United States
British Heart Foundation - United Kingdom
PubMed
32219386
PubMed Central
PMC7157181
DOI
10.1001/jama.2020.1906
PII: 2763950
Knihovny.cz E-resources
- MeSH
- Benzhydryl Compounds adverse effects therapeutic use MeSH
- Diabetes Mellitus, Type 2 blood complications drug therapy MeSH
- Double-Blind Method MeSH
- Ventricular Dysfunction, Left drug therapy MeSH
- Sodium-Glucose Transporter 2 Inhibitors adverse effects therapeutic use MeSH
- Glucosides adverse effects therapeutic use MeSH
- Glycated Hemoglobin analysis MeSH
- Hypoglycemic Agents therapeutic use MeSH
- Cardiovascular Diseases mortality MeSH
- Middle Aged MeSH
- Humans MeSH
- Placebos therapeutic use MeSH
- Aged MeSH
- Heart Failure complications drug therapy physiopathology MeSH
- Stroke Volume drug effects MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Clinical Trial, Phase III MeSH
- Multicenter Study MeSH
- Research Support, Non-U.S. Gov't MeSH
- Randomized Controlled Trial MeSH
- Comparative Study MeSH
- Names of Substances
- Benzhydryl Compounds MeSH
- dapagliflozin MeSH Browser
- Sodium-Glucose Transporter 2 Inhibitors MeSH
- Glucosides MeSH
- Glycated Hemoglobin A MeSH
- Hypoglycemic Agents MeSH
- Placebos MeSH
IMPORTANCE: Additional treatments are needed for heart failure with reduced ejection fraction (HFrEF). Sodium-glucose cotransporter 2 (SGLT2) inhibitors may be an effective treatment for patients with HFrEF, even those without diabetes. OBJECTIVE: To evaluate the effects of dapagliflozin in patients with HFrEF with and without diabetes. DESIGN, SETTING, AND PARTICIPANTS: Exploratory analysis of a phase 3 randomized trial conducted at 410 sites in 20 countries. Patients with New York Heart Association classification II to IV with an ejection fraction less than or equal to 40% and elevated plasma N-terminal pro B-type natriuretic peptide were enrolled between February 15, 2017, and August 17, 2018, with final follow-up on June 6, 2019. INTERVENTIONS: Addition of once-daily 10 mg of dapagliflozin or placebo to recommended therapy. MAIN OUTCOMES AND MEASURES: The primary outcome was the composite of an episode of worsening heart failure or cardiovascular death. This outcome was analyzed by baseline diabetes status and, in patients without diabetes, by glycated hemoglobin level less than 5.7% vs greater than or equal to 5.7%. RESULTS: Among 4744 patients randomized (mean age, 66 years; 1109 [23%] women; 2605 [55%] without diabetes), 4742 completed the trial. Among participants without diabetes, the primary outcome occurred in 171 of 1298 (13.2%) in the dapagliflozin group and 231 of 1307 (17.7%) in the placebo group (hazard ratio, 0.73 [95% CI, 0.60-0.88]). In patients with diabetes, the primary outcome occurred in 215 of 1075 (20.0%) in the dapagliflozin group and 271 of 1064 (25.5%) in the placebo group (hazard ratio, 0.75 [95% CI, 0.63-0.90]) (P value for interaction = .80). Among patients without diabetes and a glycated hemoglobin level less than 5.7%, the primary outcome occurred in 53 of 438 patients (12.1%) in the dapagliflozin group and 71 of 419 (16.9%) in the placebo group (hazard ratio, 0.67 [95% CI, 0.47-0.96]). In patients with a glycated hemoglobin of at least 5.7%, the primary outcome occurred in 118 of 860 patients (13.7%) in the dapagliflozin group and 160 of 888 (18.0%) in the placebo group (hazard ratio, 0.74 [95% CI, 0.59-0.94]) (P value for interaction = .72). Volume depletion was reported as an adverse event in 7.3% of patients in the dapagliflozin group and 6.1% in the placebo group among patients without diabetes and in 7.8% of patients in the dapagliflozin group and 7.8% in the placebo group among patients with diabetes. A kidney adverse event was reported in 4.8% of patients in the dapagliflozin group and 6.0% in the placebo group among patients without diabetes and in 8.5% of patients in the dapagliflozin group and 8.7% in the placebo group among patients with diabetes. CONCLUSIONS AND RELEVANCE: In this exploratory analysis of a randomized trial of patients with HFrEF, dapagliflozin compared with placebo, when added to recommended therapy, significantly reduced the risk of worsening heart failure or cardiovascular death independently of diabetes status. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03036124.
5th Department of Internal Medicine Comenius University in Bratislava Bratislava Slovakia
British Heart Foundation Cardiovascular Research Centre University of Glasgow Glasgow United Kingdom
Cardiovascular Division Brigham and Women's Hospital Boston Massachusetts
Cardiovascular Division of Medicine National Cerebral and Cardiovascular Center Osaka Japan
Center for Heart Diseases University Hospital Wroclaw Medical University Wroclaw Poland
Clinic of Cardiology National Cardiology Hospital Sofia Bulgaria
Department Cardiology Medical University of Lodz Lodz Poland
Department of Cardiology Copenhagen University Hospital Copenhagen Denmark
Department of Cardiology Gentofte University Hospital Copenhagen Copenhagen Denmark
Department of Cardiology Medanta Gurgaon Haryana India
Department of Cardiology Montreal Heart Institute Montreal Ontario Canada
Department of Cardiology University of Minnesota Minneapolis
Department of Internal Medicine Tan Tao University Tan Duc Vietnam
Department of Medicine Saarland University Hospital Homburg Saar Germany
Division of Cardiac Surgery St Michael's Hospital University of Toronto Toronto Ontario Canada
Division of Cardiology Instituto Cardiovascular de Buenos Aires Buenos Aires Argentina
Division of Cardiology Taipei Veterans General Hospital Taipei Taiwan
Heart and Vascular Center Semmelweis University Budapest Hungary
National Yang Ming University Taipei Taiwan
Section of Endocrinology Yale University School of Medicine New Haven Connecticut
St Luke's Mid America Heart Institute University of Missouri Kansas City Kansas City
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ClinicalTrials.gov
NCT03036124
