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Evaluation of the effect of sodium-glucose co-transporter 2 inhibition with empagliflozin on morbidity and mortality of patients with chronic heart failure and a reduced ejection fraction: rationale for and design of the EMPEROR-Reduced trial.

Publication ,  Journal Article
Packer, M; Butler, J; Filippatos, GS; Jamal, W; Salsali, A; Schnee, J; Kimura, K; Zeller, C; George, J; Brueckmann, M; Anker, SD; Zannad, F ...
Published in: Eur J Heart Fail
October 2019

Drugs that inhibit the sodium-glucose co-transporter 2 (SGLT2) have been shown to reduce the risk of hospitalizations for heart failure in patients with type 2 diabetes. In populations that largely did not have heart failure at the time of enrolment, empagliflozin, canagliflozin and dapagliflozin decreased the risk of serious new-onset heart failure events by ≈30%. In addition, in the EMPA-REG OUTCOME trial, empagliflozin reduced the risk of both pump failure and sudden deaths, the two most common modes of death among patients with heart failure. In none of the three trials could the benefits of SGLT2 inhibitors on heart failure be explained by the actions of these drugs as diuretics or anti-hyperglycaemic agents. These observations raise the possibility that SGLT2 inhibitors could reduce morbidity and mortality in patients with established heart failure, including those without diabetes. The EMPEROR-Reduced trial is enrolling ≈3600 patients with heart failure and a reduced left ventricular ejection fraction (≤ 40%), half of whom are expected not to have diabetes. Patients are being randomized to placebo or empagliflozin 10 mg daily, which is added to all appropriate treatment with inhibitors of the renin-angiotensin system and neprilysin, beta-blockers and mineralocorticoid receptor antagonists. The primary endpoint is the time-to-first event analysis of the combined risk of cardiovascular death and hospitalization for heart failure, but the trial will also evaluate the effects of empagliflozin on renal function, cardiovascular death, all-cause mortality, and recurrent hospitalization events. By adjusting eligibility based on natriuretic peptide levels to the baseline ejection fraction, the trial will preferentially enrol high-risk patients. A large proportion of the participants is expected to have an ejection fraction < 30%, and the estimated annual event rate is expected to be at least 15%. The EMPEROR-Reduced trial is well-positioned to determine if the addition of empagliflozin can add meaningfully to current approaches that have established benefits in the treatment of chronic heart failure with left ventricular systolic dysfunction.

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Published In

Eur J Heart Fail

DOI

EISSN

1879-0844

Publication Date

October 2019

Volume

21

Issue

10

Start / End Page

1270 / 1278

Location

England

Related Subject Headings

  • Stroke Volume
  • Sodium-Glucose Transporter 2 Inhibitors
  • Randomized Controlled Trials as Topic
  • Humans
  • Heart Failure
  • Glucosides
  • Chronic Disease
  • Cardiovascular System & Hematology
  • Benzhydryl Compounds
  • 3201 Cardiovascular medicine and haematology
 

Citation

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Packer, M., Butler, J., Filippatos, G. S., Jamal, W., Salsali, A., Schnee, J., … EMPEROR-Reduced Trial Committees and Investigators, . (2019). Evaluation of the effect of sodium-glucose co-transporter 2 inhibition with empagliflozin on morbidity and mortality of patients with chronic heart failure and a reduced ejection fraction: rationale for and design of the EMPEROR-Reduced trial. Eur J Heart Fail, 21(10), 1270–1278. https://doi.org/10.1002/ejhf.1536
Packer, Milton, Javed Butler, Gerasimos S. Filippatos, Waheed Jamal, Afshin Salsali, Janet Schnee, Karen Kimura, et al. “Evaluation of the effect of sodium-glucose co-transporter 2 inhibition with empagliflozin on morbidity and mortality of patients with chronic heart failure and a reduced ejection fraction: rationale for and design of the EMPEROR-Reduced trial.Eur J Heart Fail 21, no. 10 (October 2019): 1270–78. https://doi.org/10.1002/ejhf.1536.
Packer M, Butler J, Filippatos GS, Jamal W, Salsali A, Schnee J, Kimura K, Zeller C, George J, Brueckmann M, Anker SD, Zannad F, EMPEROR-Reduced Trial Committees and Investigators. Evaluation of the effect of sodium-glucose co-transporter 2 inhibition with empagliflozin on morbidity and mortality of patients with chronic heart failure and a reduced ejection fraction: rationale for and design of the EMPEROR-Reduced trial. Eur J Heart Fail. 2019 Oct;21(10):1270–1278.
Journal cover image

Published In

Eur J Heart Fail

DOI

EISSN

1879-0844

Publication Date

October 2019

Volume

21

Issue

10

Start / End Page

1270 / 1278

Location

England

Related Subject Headings

  • Stroke Volume
  • Sodium-Glucose Transporter 2 Inhibitors
  • Randomized Controlled Trials as Topic
  • Humans
  • Heart Failure
  • Glucosides
  • Chronic Disease
  • Cardiovascular System & Hematology
  • Benzhydryl Compounds
  • 3201 Cardiovascular medicine and haematology