The DOI matches its Crossref record; 9 of the 10 references it cites were found in a registry or an index.
Cardiovascular and Renal Outcomes with Empagliflozin in Heart Failure
Open accessAbstract
BACKGROUNDSodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the risk of hospitalization for heart failure in patients regardless of the presence or absence of diabetes.More evidence is needed regarding the effects of these drugs in patients across the broad spectrum of heart failure, including those with a markedly reduced ejection fraction. METHODSIn this double-blind trial, we randomly assigned 3730 patients with class II, III, or IV heart failure and an ejection fraction of 40% or less to receive empagliflozin (10 mg once daily) or placebo, in addition to recommended therapy.The primary outcome was a composite of cardiovascular death or hospitalization for worsening heart failure. RESULTSDuring a median of 16 months, a primary outcome event occurred in 361 of 1863 patients (19.4%) in the empagliflozin group and in 462 of 1867 patients (24.7%) in the placebo group (hazard ratio for cardiovascular death or hospitalization for heart failure, 0.75; 95% confidence interval [CI], 0.65 to 0.86; P<0.001).The effect of empagliflozin on the primary outcome was consistent in patients regardless of the presence or absence of diabetes.The total number of hospitalizations for heart failure was lower in the empagliflozin group than in the placebo group (hazard ratio, 0.70; 95% CI, 0.58 to 0.85; P<0.001).The annual rate of decline in the estimated glomerular filtration rate was slower in the empagliflozin group than in the placebo group (-0.55 vs. -2.28ml per minute per 1.73 m 2 of body-surface area per year, P<0.001), and empagliflozin-treated patients had a lower risk of serious renal outcomes.Uncomplicated genital tract infection was reported more frequently with empagliflozin. CONCLUSIONSAmong patients receiving recommended therapy for heart failure, those in the empagliflozin group had a lower risk of cardiovascular death or hospitalization for heart failure than those in the placebo group, regardless of the presence or absence of diabetes.(Funded by Boehringer Ingelheim and Eli Lilly; EMPEROR-Reduced ClinicalTrials.govnumber, NCT03057977.
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The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Subgroup analyses from DAPA-CKD (117) and analyses from the EMPEROR heart failure trials suggest that SGLT2 inhibitors are safe and effective at eGFR levels of >20 mL/min/1.73m 2 .”
From 11. Chronic Kidney Disease and Risk Management: Standards of Care in Diabetes—2025 (2025) · cites this paper as [119]
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
“Direct evidence is provided by the DAPA-CKD, SCORED, EMPEROR-Reduced, and EMPEROR-Preserved trials, which enrolled such participants by design.”
From KDIGO 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease (2022) · cites this paper as [101]
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
“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 [101]
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
“enrollment criteria included eGFR >60 mL/min/1.73m 2 , but efficacy was seen at eGFR >20 mL/min/1.73m 2 in people with heart failure.”
From 11. Chronic Kidney Disease and Risk Management: Standards of Care in Diabetes—2026 (2026) · cites this paper as [135]
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 [303]
Experimental — accuracy not yet measured
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“and the Empagliflozin Outcome Trial in Patients With Chronic Heart Failure (EMPEROR) trials (which provided clear evidence of efficacy and safety for empagliflozin among patients with eGFR ≥20 mL/min/1.73 m2 and HF) (54,57,58).”
From Diabetes management in chronic kidney disease: a consensus report by the American Diabetes Association (ADA) and Kidney Disease: Improving Global Outcomes (KDIGO) (2022) · cites this paper as [58]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Clinical trials, such as EMPEROR-REDUCED (empagliflozin) and DAPA-CKD (dapagliflozin), have shown that SGLT-2 inhibitors have benefits in patients with heart failure and chronic kidney disease, regardless of the presence of diabetes.38,39”
From Tirzepatide: Clinical review of the twincretin injectable (2023) · cites this paper as [39]
The cited source says what the claim attributes to it.
In the citing paper
“The primary outcome among those with an eGFR $ 60 ml/min per 1.73 m 2 was HR: 0.67; 95% CI: 0.55 -0.83 and for those with eGFR < 60 ml/min per 1.73 m 2 was HR: 0.83; 95% CI: 0.69 -1.00.”
From KDIGO 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease (2022) · cites this paper as [101]
The cited source says what the claim attributes to it.
In the citing paper
“As seen in DAPA-HF, the primary outcome was similarly reduced for individuals with and without diabetes.”
From KDIGO 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease (2022) · cites this paper as [101]
The cited source says what the claim attributes to it.
In the citing paper
“the primary outcome of cardiovascular death or heart failure hospitalization occurred in 19.4% of the empagli fl ozin group and 24.7% of the placebo group (HR: 0.75; 95% CI: 0.65 -0.86).”
From KDIGO 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease (2022) · cites this paper as [101]
The cited source says what the claim attributes to it.
In the citing paper
“A composite kidney outcome HR of 0.50 (95% CI: 0.32 -0.77) was also reported.”
From KDIGO 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease (2022) · cites this paper as [101]
The cited source says what the claim attributes to it.
In the citing paper
“Similar results were obtained in clinical trials with empagliflozin (303).”
From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2025 (2025) · cites this paper as [303]
The cited source says what the claim attributes to it.
In the citing paper
“Similar results were obtained in clinical trials with empagliflozin (291).”
From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2026 (2026) · cites this paper as [291]
The check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“The EMPEROR-Reduced 101 and EMPEROR-Preserved 102 trials, although not an exclusive CKD population, did allow enrollment of patients with an eGFR as low as 20 ml/min per 1.73 m 2.”
From KDIGO 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease (2022) · cites this paper as [101]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“The EMPA-REG trial enrolled over 7000 patients with T2D, baseline glycated hemoglobin (HbA1c) of 7% -10%, established CVD (almost 100%), and an eGFR of at least 30 ml/min per 1.73 m 2 . 101”
From KDIGO 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease (2022) · cites this paper as [101]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“The EMPEROR-Reduced and EMPEROR-Preserved trials, although not exclusive CKD populations, did allow enrollment participants with an eGFR as low as 20 ml/min per 1.73 m 2 .”
From KDIGO 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease (2022) · cites this paper as [101]
Experimental — accuracy not yet measuredIn the citing paper
“The EMPEROR-Reduced (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Reduced Ejection Fraction) trial demonstrated a benefit of SGLT2 inhibition with empagliflozin to reduce both the risk and rate of heart failure hospitalizations.7”
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 [7]
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 [7]
In the citing paper
“As previously reported,7 the 2 groups comprised patients with mild, moderate, and severe heart failure, as reflected by left ventricular ejection fraction and circulating levels of NT-proBNP, and were well-balanced with respect to baseline characteristics.”
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 [7]
In the citing paper
“In the EMPEROR-Reduced trial, empagliflozin reduced the risk of cardiovascular death or hospitalization for heart failure, a benefit that was driven primarily by an effect of the drug to reduce first and recurrent admissions for worsening heart failure.7”
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 [7]
In the citing paper
“In our original publication and in a meta-analysis of the DAPA-HF and EMPEROR-Reduced trials, we noted a somewhat lesser benefit in patients with ejection fraction of 31% to 40% and in patients with class III symptoms.”
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 [7]
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 [8]
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
“Multiple SGLT2i trials included subsets of participants without diabetes, who appear to have derived similar benefits as those with T2D, 8,14,18”
In the citing paper
“Treatment with empagliflozin improved quality of life.496”
From 2023 ESC guidelines for the management of cardiovascular disease in patients with diabetes. (2023) · cites this paper as [496]
In the citing paper
“The risk of a prespeci fi ed renal composite outcome (chronic dialysis, renal transplantation, or a sustained reduction in eGFR) was lower in the empagli fl ozin group than in the placebo group (1.6% in the empaglifl ozin group vs. 3.1% in the placebo group; HR 0.50 [95% CI 0.32 -0.77]).”
From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2023 (2023) · cites this paper as [200]
In the citing paper
“Over a median follow-up of 16 months, those in the empagli fl ozin-treated group had a reduced risk of the primary outcome (HR 0.75 [95% CI 0.65 -0.86]; P < 0.001) and fewer total hospitalizations for heart failure (HR 0.70 [95% CI 0.58 -0.85]; P < 0.001).”
From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2023 (2023) · cites this paper as [200]
In the citing paper
“Over a median follow-up of 16 months, those in the empagli fl ozin-treated group had a reduced risk of the primary outcome (HR 0.75 [95% CI 0.65 -0.86]; P < 0.001) and fewer total hospitalizations for heart failure (HR 0.70 [95% CI 0.58 -0.85]; P < 0.001).”
From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2023 (2023) · cites this paper as [200]
In the citing paper
“The effect of empagli fl ozin on the primary outcome was consistent irrespective of diabetes diagnosis at baseline.”
From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2023 (2023) · cites this paper as [200]
In the citing paper
“Moreover, in the recent EMPEROR-Reduced trial (Empagliflozin Outcome Trial in Patients with Chronic Heart Failure and a Reduced Ejection Fraction), SGLT2 inhibition did reduce renal events significantly, although that trial used a different renal composite outcome and had more renal events than in DAPA-HF (88 versus 67).”
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 [21]
In the citing paper
“More recently, in a large trial using empagliflozin in patients with HFrEF, the rate of decline in eGFR was 2.28 (SD 0.23) mL·min–1·1.73 m–2 per year, which was reduced to 0.55 (0.23) in the SGLT2 inhibitor group.21”
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 [21]
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Citations
Cites
Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes
Neal, B., Perkovic, V., Mahaffey, K. W., de Zeeuw, D., Fulcher, G., Erondu, N., Shaw, W., Law, G., Desai, M., & Matthews, D. R. (2017) · New England Journal of Medicine · doi:10.1056/nejmoa1611925 · Cited by 7,830
Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction
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., et al. (2019) · New England Journal of Medicine · doi:10.1056/nejmoa1911303 · Cited by 7,140
Self-citationZelniker, T. A., Wiviott, S. D., Raz, I., Im, K., Goodrich, E. L., Bonaca, M. P., Mosenzon, O., Kato, E. T., Cahn, A., Furtado, R. H. M., et al. (2019) · The Lancet · doi:10.1016/s0140-6736(18)32590-x · Cited by 2,845
Effect of dapagliflozin on heart failure and mortality in type 2 diabetes mellitus
Kato, E. T., Silverman, M. G., Mosenzon, O., Zelniker, T. A., Cahn, A., Furtado, R. H. M., Kuder, J., Murphy, S. A., Bhatt, D. L., Leiter, L. A., et al. (2019) · Circulation · doi:10.1161/circulationaha.119.040130 · Cited by 557
FITCHETT, D. H., Inzucchi, S. E., Cannon, C. P., McGuire, D. K., Scirica, B. M., Johansen, O. E., Sambevski, S., Kaspers, S., Pfarr, E., George, J. T., et al. (2019) · Circulation · doi:10.1161/circulationaha.118.037778 · Cited by 360
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Packer, M. (2020) · Diabetes Care · doi:10.2337/dci19-0074 · Cited by 247
Self-citationDonnan, J. R., Grandy, C. A., Chibrikov, E., Marra, C. A., Aubrey-Bassler, K., Johnston, K., Swab, M., Hache, J., Curnew, D., Nguyen, H., et al. (2019) · BMJ Open · doi:10.1136/bmjopen-2018-022577 · Cited by 222
Natriuretic Peptides as Inclusion Criteria in Clinical Trials
Ibrahim, N. E., Burnett, J. C. J., Butler, J., Camacho, A., Felker, G. M., Fiuzat, M., O’Connor, C. J., Solomon, S. D., Vaduganathan, M., Zile, M. R., et al. (2020) · JACC Heart Failure · doi:10.1016/j.jchf.2019.12.010 · Cited by 83
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2021 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure
McDonagh, T. A., Metra, M., Adamo, M., Gardner, R. S., Baumbach, A., Böhm, M., Burri, H., Butler, J., Čelutkienė, J., Chioncel, O., et al. (2021) · European Heart Journal · doi:10.1093/eurheartj/ehab368 · Cited by 13,344
Self-citation2021 ESC Guidelines on cardiovascular disease prevention in clinical practice
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Self-citation2023 ESC Guidelines for the management of acute coronary syndromes
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Empagliflozin in heart failure with a preserved ejection fraction
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Metadata
- Authors
- Packer, M., Anker, S. D., Butler, J., Filippatos, G., Pocock, S. J., Carson, P., Januzzi, J., Verma, S., Tsutsui, H., Brueckmann, M., Jamal, W., Kimura, K., Schnee, J., Zeller, C., Cotton, D., Bocchi, E., Böhm, M., Choi, D.-J., Chopra, V., Chuquiure, E., Giannetti, N., Janssens, S., Zhang, J., Gonzalez Juanatey, J. R., Kaul, S., Brunner-La Rocca, H.-P., Merkely, B., Nicholls, S. J., Perrone, S., Pina, I., Ponikowski, P., Sattar, N., Senni, M., Seronde, M.-F., Spinar, J., Squire, I., Taddei, S., Wanner, C., & Zannad, F.
- Affiliations
- University of Leicester (GB)
- Harvard University (US)
- St. Michael's Hospital (CA)
- Kyushu University (JP)
- Boehringer Ingelheim (Germany) (DE)
- Seoul National University (KR)
- From Baylor Heart and Vascular Institute, Baylor University Medical Center, Dallas (M.P.); Imperial College (M.P.) and the Department of Medical Statistics, London School of Hygiene and Tropical Medicine (S.J.P.), London, BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow (N.S.), and the Department of Cardiovascular Sciences, University of Leicester and National Institute for Health Research Biomedical Research Centre, Glenfield Hospital, Leicester (I.S.) — all in the United...
- Cedars-Sinai Medical Center (US)
- University of Pisa (IT)
- ORCID
- Packer, Milton
- Anker, Stefan D.
- Butler, Javed
- Filippatos, Gerasimos
- Pocock, Stuart J.
- Januzzi, James
- Verma, Subodh
- Tsutsui, Hiroyuki
- Brueckmann, Martina
- Jamal, Waheed
- Kimura, Karen
- Schnee, Janet
- Zeller, Cordula
- Cotton, Daniel
- Bocchi, Edimar
- Böhm, Michael
- Choi, Dong-Ju
- Chopra, Vijay
- Giannetti, Nadia
- Janssens, Stefan
- Zhang, Jian
- Kaul, Sanjay
- Nicholls, Stephen J.
- Perrone, Sergio
- Ponikowski, Piotr
- Sattar, Naveed
- Senni, Michele
- Seronde, Marie-France
- Squire, Iain
- Taddei, Stefano
- Wanner, Christoph
- Zannad, Faiez
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2020-10-08
- Volume
- 383
- Issue
- 15
- Pages
- 1413-1424
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W3081830235
- Semantic Scholar
- 9f762448aff37cda38166e57ac40bc13f0005f51
- Cited by
- 5,206
- References
- 10
- Citations by year
- 2026: 638 · 2025: 757 · 2024: 820 · 2023: 965 · 2022: 936 · 2021: 910 · 2020: 163
- FWCI
- 459.86
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (acceptedVersion, cc-by-sa)
- HAL (submittedVersion, other-oa)
- CINECA IRIS Institutial research information system (University of Pisa) (submittedVersion, other-oa)
- Radboud Repository (Radboud University) (submittedVersion)
- BOA (University of Milano-Bicocca) (submittedVersion)
- Research Publications (Maastricht University) (submittedVersion, other-oa)
- Figshare (submittedVersion, cc-by)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
- Lirias (submittedVersion)
- Radboud Repository (Radboud University) (submittedVersion, other-oa)
- Funders
- Boehringer Ingelheim
- Eli Lilly
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Failure Treatment and Management
- Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Keywords
- empagliflozin, SGLT2 inhibitors, heart failure with reduced ejection fraction, cardiovascular mortality, hospitalization for worsening heart failure, renal outcomes, estimated glomerular filtration rate decline, genital tract infection, diabetes status, EMPEROR-Reduced trial
- MeSH terms
- Sodium-Glucose Transporter 2 Inhibitors, Aged, Benzhydryl Compounds, Cardiovascular Diseases, Diabetes Mellitus, Type 2, Double-Blind Method, Female, Glomerular Filtration Rate, Glucosides, Heart Failure, Hospitalization, Humans, Male, Middle Aged, Stroke Volume, Proportional Hazards Models, Disease Progression, Renal Insufficiency, Chronic
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