@article{3105582,
    title = "Evaluation of the effects of sodium–glucose co-transporter 2 inhibition with empagliflozin on morbidity and mortality in patients with chronic heart failure and a preserved ejection fraction: rationale for and design of the EMPEROR-Preserved Trial",
    author = "Anker, S.D. 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 Zannad, F. and Packer, M. and Packer, M. and Butler, J. and Filippatos, G.S. 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 Gomez Mesa, J.E. and Spinar, J. and Böhm, M. and Merkely, B. and Chopra, V. and Senni, M. and Taddi, S. and Tsutsui, H. and Chuquiure, E. and La Rocca, H.P.B. and Ponikowski, P. and Vinereanu, D. and Sim, D. and Choi, D.-J. 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-Preserved Trial Committees and Investigators",
    journal = "European Journal of Heart Failure",
    year = "2019",
    volume = "21",
    number = "10",
    pages = "1279-1287",
    publisher = "John Wiley and Sons Ltd",
    doi = "10.1002/ejhf.1596",
    keywords = "empagliflozin;  placebo;  sodium glucose cotransporter 2;  benzhydryl derivative;  empagliflozin;  glucoside, adult;  Article;  cause of death;  comorbidity;  controlled study;  disease association;  enzyme inhibition;  estimated glomerular filtration rate;  female;  follow up;  heart failure with preserved ejection fraction;  hospitalization;  human;  kidney function;  major clinical study;  male;  morbidity;  mortality;  non insulin dependent diabetes mellitus;  priority journal;  prospective study;  randomized controlled trial;  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 = "Background: The principal biological processes that characterize heart failure with a preserved ejection fraction (HFpEF) are systemic inflammation, epicardial adipose tissue accumulation, coronary microcirculatory rarefaction, myocardial fibrosis and vascular stiffness; the resulting impairment of left ventricular and aortic distensibility (especially when accompanied by impaired glomerular function and sodium retention) causes increases in cardiac filling pressures and exertional dyspnoea despite the relative preservation of left ventricular ejection fraction. Independently of their actions on blood glucose, sodium–glucose co-transporter 2 (SGLT2) inhibitors exert a broad range of biological effects (including actions to inhibit cardiac inflammation and fibrosis, antagonize sodium retention and improve glomerular function) that can ameliorate the pathophysiological derangements in HFpEF. Such SGLT2 inhibitors exert favourable effects in experimental models of HFpEF and have been found in large-scale trials to reduce the risk for serious heart failure events in patients with type 2 diabetes, many of whom were retrospectively identified as having HFpEF. Study design: The EMPEROR-Preserved Trial is enrolling ≈5750 patients with HFpEF (ejection fraction >40%), with and without type 2 diabetes, who are randomized to receive placebo or empagliflozin 10 mg/day, which is added to all appropriate treatments for HFpEF and co-morbidities. Study aims: The primary endpoint is the time-to-first-event analysis of the combined risk for cardiovascular death or hospitalization for heart failure. The trial will also evaluate the effects of empagliflozin on renal function, cardiovascular death,. all-cause mortality and recurrent hospitalization events, and will assess a wide range of biomarkers that reflect important pathophysiological mechanisms that may drive the evolution of HFpEF. The EMPEROR-Preserved Trial is well positioned to determine if empagliflozin can have a meaningful impact on the course of HFpEF, a disorder for which there are currently few therapeutic options. © 2019 The Authors. European Journal of Heart Failure © 2019 European Society of Cardiology"
}