{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T19:16:40Z","timestamp":1784747800627,"version":"3.55.0"},"reference-count":36,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T00:00:00Z","timestamp":1768694400000},"content-version":"vor","delay-in-days":2378,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2019,7,16]],"date-time":"2019-07-16T00:00:00Z","timestamp":1563235200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2019,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Drugs that inhibit the sodium\u2013glucose 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 \u224830%. 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 \u22483600 patients with heart failure and a reduced left ventricular ejection fraction (\u2264\u200940%), 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\u2013angiotensin 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 &amp;lt;\u200930%, 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.<\/jats:p>","DOI":"10.1002\/ejhf.1536","type":"journal-article","created":{"date-parts":[[2019,7,16]],"date-time":"2019-07-16T03:05:33Z","timestamp":1563246333000},"page":"1270-1278","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":130,"title":["Evaluation of the Effect of Sodium\u2013Glucose 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"],"prefix":"10.1093","volume":"21","author":[{"given":"Milton","family":"Packer","sequence":"first","affiliation":[{"name":"Baylor Heart and Vascular Institute, Baylor University Medical Center , Dallas, TX ,","place":["USA"]},{"name":"Imperial College , London ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javed","family":"Butler","sequence":"additional","affiliation":[{"name":"University of Mississippi School of Medicine , Jackson, MI ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerasimos S.","family":"Filippatos","sequence":"additional","affiliation":[{"name":"Department of Cardiology, National and Kapodistrian University of Athens , Athens ,","place":["Greece"]},{"name":"School of Medicine, Athens University Hospital Attikon , Athens ,","place":["Greece"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Waheed","family":"Jamal","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim International GmbH , Ingelheim ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Afshin","family":"Salsali","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim Pharmaceuticals , Ridgefield, CT ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janet","family":"Schnee","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim Pharmaceuticals , Ridgefield, CT ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Kimura","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim Canada Ltd. , Burlington ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cordula","family":"Zeller","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim Pharma GmbH & Co. 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