The DOI matches its Crossref record; 21 of the 21 references it cites were found in a registry or an index.
Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction
Open accessAbstract
BACKGROUND: In patients with type 2 diabetes, inhibitors of sodium-glucose cotransporter 2 (SGLT2) reduce the risk of a first hospitalization for heart failure, possibly through glucose-independent mechanisms. More data are needed regarding the effects of SGLT2 inhibitors in patients with established heart failure and a reduced ejection fraction, regardless of the presence or absence of type 2 diabetes. METHODS: In this phase 3, placebo-controlled trial, we randomly assigned 4744 patients with New York Heart Association class II, III, or IV heart failure and an ejection fraction of 40% or less to receive either dapagliflozin (at a dose of 10 mg once daily) or placebo, in addition to recommended therapy. The primary outcome was a composite of worsening heart failure (hospitalization or an urgent visit resulting in intravenous therapy for heart failure) or cardiovascular death. RESULTS: Over a median of 18.2 months, the primary outcome occurred in 386 of 2373 patients (16.3%) in the dapagliflozin group and in 502 of 2371 patients (21.2%) in the placebo group (hazard ratio, 0.74; 95% confidence interval [CI], 0.65 to 0.85; P<0.001). A first worsening heart failure event occurred in 237 patients (10.0%) in the dapagliflozin group and in 326 patients (13.7%) in the placebo group (hazard ratio, 0.70; 95% CI, 0.59 to 0.83). Death from cardiovascular causes occurred in 227 patients (9.6%) in the dapagliflozin group and in 273 patients (11.5%) in the placebo group (hazard ratio, 0.82; 95% CI, 0.69 to 0.98); 276 patients (11.6%) and 329 patients (13.9%), respectively, died from any cause (hazard ratio, 0.83; 95% CI, 0.71 to 0.97). Findings in patients with diabetes were similar to those in patients without diabetes. The frequency of adverse events related to volume depletion, renal dysfunction, and hypoglycemia did not differ between treatment groups. CONCLUSIONS: Among patients with heart failure and a reduced ejection fraction, the risk of worsening heart failure or death from cardiovascular causes was lower among those who received dapagliflozin than among those who received placebo, regardless of the presence or absence of diabetes. (Funded by AstraZeneca; DAPA-HF ClinicalTrials.gov number, NCT03036124.).
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In the citing paper
“Importantly, 55% of patients in this trial did not have diabetes at baseline, and the effect of dapagliflozin was similar at any hemoglobin A1c level.40”
From CCS/CHFS Heart Failure Guidelines Update: Defining a New Pharmacologic Standard of Care for Heart Failure With Reduced Ejection Fraction (2021) · cites this paper as [40]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“the secondary outcome of worsening kidney function (de fi ned as a sustained $ 50% reduction in eGFR, kidney failure, or death from kidney causes) occurred in 1.2% of the dapagli fl ozin arm and 1.6% of the placebo arm (HR: 0.71; 95% CI: 0.44 -1.16), which was not statistically signi fi cant ( P ¼ 0.17).”
From KDIGO 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease (2022) · cites this paper as [100]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“In the DAPA-HF trial, major hypoglycemia, lower-limb amputation, and fracture occurred infrequently and the incidences were similar between the 2 treatment groups.”
From KDIGO 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease (2022) · cites this paper as [100]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“SGLT2 inhibitors reduce the incidence of heart failure and improve heart failurerelated outcomes, including hospitalization for heart failure and heart failure-related symptoms, in people with diabetes with preserved or reduced ejection fraction (250,(255)(256)(257)(298)(299)(300)(301)(302)(303)(304)(305)(306).”
From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2025 (2025) · cites this paper as [299]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“The lower risk of hospitalization for heart failure or death from cardiovascular causes in the dapagliflozin group than in the placebo group is consistent with the results of two previous trials of dapagliflozin, the DECLARE-TIMI 58 (Dapagliflozin Effect on Cardiovascular Events-Thrombolysis in Myocardial Infarction 58) and DAPA-HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure”
From Dapagliflozin in Patients with Chronic Kidney Disease (2020) · cites this paper as [18]
The cited source says what the claim attributes to it.
In the citing paper
“SGLT2 inhibition is also known to benefit patients with heart failure and a reduced ejection fraction.471”
From Glucagon-like peptide-1 receptor: mechanisms and advances in therapy (2024) · cites this paper as [471]
The cited source says what the claim attributes to it.
In the citing paper
“Over a median 18-month follow-up of 4744 patients with HFrEF, treatment with dapagliflozin significantly reduced the composite primary end point of time to first worsening of HF or death from CV causes (hazard ratio [HR], 0.74 [95% CI 0.65-0.85]; P < 0.001), as well as HHF (HR, 0.70 [95% CI 0.59 - 0.83]) and CV death (HR, 0.82 [95% CI 0.69 - 0.98]).”
From CCS/CHFS Heart Failure Guidelines Update: Defining a New Pharmacologic Standard of Care for Heart Failure With Reduced Ejection Fraction (2021) · cites this paper as [40]
The cited source says what the claim attributes to it.
In the citing paper
“SGLT2 inhibitor treatment was safe with no excess in hypovolemia, hypoglycemia, or renal side effects compared with placebo.”
From CCS/CHFS Heart Failure Guidelines Update: Defining a New Pharmacologic Standard of Care for Heart Failure With Reduced Ejection Fraction (2021) · cites this paper as [40]
The cited source says what the claim attributes to it.
In the citing paper
“The primary outcome was similarly reduced for individuals with or without diabetes, with no effect of heterogeneity by diabetes status.”
From KDIGO 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease (2022) · cites this paper as [100]
The cited source says what the claim attributes to it.
In the citing paper
“The primary outcome was also similar among those with an eGFR $ 60 ml/min per 1.73 m 2 (HR: 0.76; 95% CI: 0.63 -0.92) or < 60 ml/min per 1.73 m 2 (HR: 0.72; 95% CI: 0.59 -0.86).”
From KDIGO 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease (2022) · cites this paper as [100]
The cited source says what the claim attributes to it.
In the citing paper
“the primary outcome of cardiovascular death, heart failure hospitalization, or urgent heart failure visit occurred in 16.3% of the dapagli fl ozin group and 21.2% of the placebo group (HR: 0.74; 95% CI: 0.65 -0.85).”
From KDIGO 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease (2022) · cites this paper as [100]
The cited source says what the claim attributes to it.
In the citing paper
“However, notably, SGLT2i have been studied among patients without T2D who have CKD in the DAPA-CKD trial (and the soonto-be-published EMPA-KIDNEY trial) or who have heart failure (in the DAPA-HF, EMPEROR-Reduced, and EMPEROR-Preserved trials) and did not confer any increased risk of severe hypoglycemia or diabetic ketoacidosis among individuals without T2D.”
From KDIGO 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease (2022) · cites this paper as [100]
The cited source says what the claim attributes to it.
In the citing paper
“The effect of dapagliflozin on the primary outcome was consistent regardless of the presence or absence of type 2 diabetes (299).”
From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2025 (2025) · cites this paper as [299]
The cited source says what the claim attributes to it.
In the citing paper
“lower risk of first worsening heart failure event (HR 0.70 [95% CI 0.59-0.83]),”
From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2025 (2025) · cites this paper as [299]
The cited source says what the claim attributes to it.
In the citing paper
“Dapagliflozin treatment had a lower risk of the primary outcome (HR 0.74 [95% CI 0.65-0.85]),”
From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2025 (2025) · cites this paper as [299]
The cited source says what the claim attributes to it.
In the citing paper
“The effect of dapagliflozin on the primary outcome was consistent regardless of the presence or absence of type 2 diabetes (287).”
From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2026 (2026) · cites this paper as [287]
The cited source says what the claim attributes to it.
In the citing paper
“Dapagliflozin treatment had a lower risk of the primary outcome (HR 0.74 [95% CI 0.65–0.85]), lower risk of first worsening heart failure event (HR 0.70 [95% CI 0.59–0.83]), and lower risk of cardiovascular death (HR 0.82 [95% CI 0.69–0.98]) compared with placebo.”
From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2026 (2026) · cites this paper as [287]
In the citing paper
“Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been shown to reduce the risk of hospitalizations for heart failure in 8 large-scale trials, including those that focused on type 2 diabetes, heart failure with a reduced ejection fraction, and chronic kidney disease.1–8”
From Effect of Empagliflozin on the Clinical Stability of Patients With Heart Failure and a Reduced Ejection Fraction: The EMPEROR-Reduced Trial (2021) · cites this paper as [6]
In the citing paper
“Rates of worsening heart failure or cardiovascular death are lower among patients with heart failure who are treated with dapagliflozin and empagliflozin regardless of diabetes diagnosis.7,8”
From Association of race/ethnicity, gender, and socioeconomic status with sodium-glucose cotransporter 2 inhibitor use among patients with diabetes in the US (2021) · cites this paper as [7]
In the citing paper
“As for the morbidity, renal outcome and HHF, it was clear that SGLT-2i had more significant impact than finerenone, which might be explained by the special potency of SGLT-2i such as reducing blood glucose, reducing oxidative stress, losing weight, reducing uric acid, controlling blood pressure and improving renal ultrafiltration and hypoxia [65, 71–79].”
In the citing paper
“In DAPA-HF, dapagliflozin reduced the risk for worsening HF or CVD death irrespective of diabetes status (58).”
From SGLT2 inhibition for CKD and cardiovascular disease in type 2 diabetes: report of a scientific workshop sponsored by the National Kidney Foundation (2021) · cites this paper as [58]
In the citing paper
“Rates of heart failure hospitalization have been improved in recent trials including people with type 2 diabetes, most of whom also had ASCVD, with sodium -glucose cotransporter 2 (SGLT2) inhibitors (8 -11).”
From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2023 (2023) · cites this paper as [11]
In the citing paper
“Over a median of 18.2 months, the group assigned to dapagli fl ozin treatment had a lower risk of the primary outcome (HR 0.74 [95% CI 0.65 -0.85]), lower risk of fi rst worsening heart failure event (HR 0.70 [95% CI 0.59 -0.83]), and lower risk of cardiovascular death (HR 0.82 [95% CI 0.69 -0.98]) compared with placebo.”
From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2023 (2023) · cites this paper as [11]
In the citing paper
“The effect of dapagli fl ozin on the primary outcome was consistent regardless of the presence or absence of type 2 diabetes (11).”
From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2023 (2023) · cites this paper as [11]
In the citing paper
“Over a median of 18.2 months, the group assigned to dapagli fl ozin treatment had a lower risk of the primary outcome (HR 0.74 [95% CI 0.65 -0.85]), lower risk of fi rst worsening heart failure event (HR 0.70 [95% CI 0.59 -0.83]), and lower risk of cardiovascular death (HR 0.82 [95% CI 0.69 -0.98]) compared with placebo.”
From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2023 (2023) · cites this paper as [11]
In the citing paper
“Over a median of 18.2 months, the group assigned to dapagli fl ozin treatment had a lower risk of the primary outcome (HR 0.74 [95% CI 0.65 -0.85]), lower risk of fi rst worsening heart failure event (HR 0.70 [95% CI 0.59 -0.83]), and lower risk of cardiovascular death (HR 0.82 [95% CI 0.69 -0.98]) compared with placebo.”
From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2023 (2023) · cites this paper as [11]
In the citing paper
“In the DAPA-HF trial (Dapagliflozin and Prevention of Adverse-outcomes in Heart Failure), the SGLT2 inhibitor dapagliflozin reduced the incidence of the primary composite outcome of cardiovascular death or worsening heart failure (HF) in patients who had HFrEF with and without type 2 diabetes.”
From Efficacy of Dapagliflozin on Renal Function and Outcomes in Patients With Heart Failure With Reduced Ejection Fraction: Results of DAPA-HF (2021) · cites this paper as [9]
In the citing paper
“The DAPA-HF trial randomly assigned patients with HFrEF with and without type 2 diabetes in a double-blind, placebo-controlled, event-driven trial.”
From Efficacy of Dapagliflozin on Renal Function and Outcomes in Patients With Heart Failure With Reduced Ejection Fraction: Results of DAPA-HF (2021) · cites this paper as [9]
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Metadata
- Authors
- McMurray, J. J. V., Solomon, S. D., Inzucchi, S. E., Køber, L., Kosiborod, M. N., Martinez, F. A., Ponikowski, P., Sabatine, M. S., Anand, I. S., Bělohlávek, J., Böhm, M., Chiang, C.-E., Chopra, V. K., de Boer, R. A., Desai, A. S., Diez, M., Drozdz, J., Dukát, A., Ge, J., Howlett, J. G., Katova, T., Kitakaze, M., Ljungman, C. E. A., Merkely, B., Nicolau, J. C., O’Meara, E., Petrie, M. C., Vinh, P. N., Schou, M., Tereshchenko, S., Verma, S., Held, C., DeMets, D. L., Docherty, K. F., Jhund, P. S., Bengtsson, O., Sjöstrand, M., & Langkilde, A.-M.
- Affiliations
- Brigham and Women's Hospital (US)
- From the BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom (J.J.V.M., M.C.P., K.F.D., P.S.J.); the Cardiovascular Division (S.D.S., A.S.D.) and the TIMI Study Group, Brigham and Women’s Hospital and Harvard Medical School (M.S.S.) — all in Boston; Section of Endocrinology, Yale University School of Medicine, New Haven, CT (S.E.I.); Rigshospitalet Copenhagen University Hospital (L.K.) and the Department of Cardiology, Gentofte University Hospital (M. Schou),...
- Semmelweis University (HU)
- Uppsala University (SE)
- ORCID
- McMurray, John J.V.
- Solomon, Scott D.
- Inzucchi, Silvio E.
- Køber, Lars
- Kosiborod, Mikhail N.
- Ponikowski, Piotr
- Sabatine, Marc S.
- Anand, Inder S.
- Bělohlávek, Jan
- Böhm, Michael
- Chiang, Chern-En
- Chopra, Vijay K.
- Desai, Akshay S.
- Ge, Junbo
- Howlett, Jonathan G.
- Kitakaze, Masafumi
- Ljungman, Charlotta E.A.
- Merkely, Béla
- O’Meara, Eileen
- Petrie, Mark C.
- Schou, Morten
- Tereshchenko, Sergey
- Verma, Subodh
- Held, Claes
- DeMets, David L.
- Docherty, Kieran F.
- Jhund, Pardeep S.
- Bengtsson, Olof
- Sjöstrand, Mikaela
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2019-11-21
- Volume
- 381
- Issue
- 21
- Pages
- 1995-2008
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2974260792
- Semantic Scholar
- 43e5c9ff37bb98a622e70cb01c55e23a60782d69
- Cited by
- 7,140
- References
- 21
- Citations by year
- 2026: 842 · 2025: 955 · 2024: 979 · 2023: 1060 · 2022: 1138 · 2021: 1152 · 2020: 904 · 2019: 89
- FWCI
- 593.03
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- New England Journal of Medicine (publishedVersion, other-oa)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (publishedVersion, other-oa)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (acceptedVersion, cc-by-sa)
- Research Bank (Australian Catholic University) (submittedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, other-oa)
- Funders
- AstraZeneca Plc
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Failure Treatment and Management
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Function and Risk Factors
- Keywords
- dapagliflozin, SGLT2 inhibitors, heart failure with reduced ejection fraction, type 2 diabetes, cardiovascular mortality, heart failure hospitalization, hypovolemia, renal dysfunction, hypoglycemia, SGLT2 inhibition, heart failure prognosis, adverse events, glucose monitoring, heart failure with preserved ejection fraction
- MeSH terms
- Sodium-Glucose Transporter 2 Inhibitors, Aged, Benzhydryl Compounds, Cardiovascular Agents, Cardiovascular Diseases, Combined Modality Therapy, Diabetes Mellitus, Type 2, Drug Therapy, Combination, Female, Glucosides, Heart Failure, Glycated Hemoglobin, Hospitalization, Humans, Male, Middle Aged, Stroke Volume, Ventricular Dysfunction, Left, Kaplan-Meier Estimate
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