@article{3105612,
    title = "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",
    author = "Packer, M. and Butler, J. and Filippatos, G.S. and Jamal, W. and Salsali, A. and Schnee, J. and Kimura, K. and Zeller, C. and George, J. and Brueckmann, M. and Anker, S.D. and Zannad, F. and Butler, J. and Zannad, F. and George, J. and Brueckmann, M. and Perrone, S. and Nicholls, S. and Janssens, S. and Bocchi, E. and Giannetti, N. and Verma, S. and Jian, Z. and Spinar, J. and Seronde, M.-F. and Böhm, M. and Merkely, B. and Chopra, V. and Senni, M. and Taddei, S. and Tsutsui, H. and Choi, D.-J. and Chuquiure, E. and La Rocca, H.P.B. and Ponikowski, P. and Juanatey, J.R.G. and Squire, I. and Butler, J. and Januzzi, J. and Pina, I. and Pocock, S.J. and Carson, P. and Doehner, W. and Miller, A. and Haas, M. and Pehrson, S. and Komajda, M. and Anand, I. and Teerlink, J. and Rabinstein, A. and Steiner, T. and Kamel, H. and Tsivgoulis, G. and Lewis, J. and Freston, J. and Kaplowitz, N. and Mann, J. and Petrie, M. and Bernstein, R. and Cheung, A. and Green, J. and Januzzi, J. and Kaul, S. and Ping, C.L.S. and Lip, G. and Marx, N. and McCullough, P. and Mehta, C. and Rosenstock, J. and Sattar, N. and Scirica, B. and Tsutsui, H. and Wanner, C. and Welty, F.K. and Parhofer, K.G. and Clayton, T. and Pedersen, T.R. and Lees, K.R. and Konstam, M.A. and Greenberg, B. and Palmer, M. and the EMPEROR-Reduced Trial Committees and Investigators and Executive Committee and National Coordinators and Consulting Statistician and Clinical Events Committee and Scientific Excellence Committee and Data Monitoring Committee",
    journal = "European Journal of Heart Failure",
    year = "2019",
    volume = "21",
    number = "10",
    pages = "1270-1278",
    publisher = "John Wiley and Sons Ltd",
    doi = "10.1002/ejhf.1536",
    keywords = "amino terminal pro brain natriuretic peptide;  beta adrenergic receptor blocking agent;  empagliflozin;  enkephalinase inhibitor;  mineralocorticoid antagonist;  placebo;  sodium glucose cotransporter 2;  benzhydryl derivative;  empagliflozin;  glucoside, adult;  all cause mortality;  Article;  cardiovascular mortality;  cardiovascular risk;  controlled study;  double blind procedure;  drug effect;  female;  heart ejection fraction;  heart failure with preserved ejection fraction;  heart failure with reduced ejection fraction;  high risk patient;  hospital readmission;  hospitalization;  human;  kidney function;  major clinical study;  male;  morbidity;  mortality;  multicenter study;  phase 3 clinical trial;  priority journal;  randomized controlled trial;  renin angiotensin aldosterone system;  study design;  young adult;  chronic disease;  heart failure;  heart stroke volume;  mortality;  randomized controlled trial (topic), Benzhydryl Compounds;  Chronic Disease;  Glucosides;  Heart Failure;  Humans;  Randomized Controlled Trials as Topic;  Sodium-Glucose Transporter 2 Inhibitors;  Stroke Volume",
    abstract = "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. © 2019 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology."
}