Dapagliflozin in patients with heart failure and reduced ejection fraction

J. J.V. McMurray*, S. D. Solomon, S. E. Inzucchi, L. Kober, M. N. Kosiborod, F. A. Martinez, P. Ponikowski, M. S. Sabatine, I. S. Anand, J. B. Lohlavek, M. Bohm, C. E. Chiang, V. K. Chopra, R. A. De Boer, A. S. Desai, M. Diez, J. Drozdz, A. Dukat, J. Ge, J. G. HowlettT. Katova, M. Kitakaze, C. E.A. Ljungman, B. Merkely, J. C. Nicolau, E. O'Meara, M. C. Petrie, P. N. Vinh, M. Schou, S. Tereshchenko, S. Verma, C. Held, D. L. DeMets, K. F. Docherty, P. S. Jhund, O. Bengtsson, M. Sjostrand, A. M. Langkilde

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

4548 Citations (Scopus)

Abstract

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 glucoseindependent 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.

Original languageEnglish
Pages (from-to)1995-2008
Number of pages14
JournalNew England Journal of Medicine
Volume381
Issue number21
DOIs
Publication statusPublished - 21 Nov 2019
Externally publishedYes

Bibliographical note

Funding Information:
Supported by AstraZeneca.

Publisher Copyright:
© 2019 Massachusetts Medical Society.

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