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

Anker, S. D. et al. (2019) 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. European Journal of Heart Failure, 21(10), pp. 1279-1287. (doi: 10.1002/ejhf.1596) (PMID:31523904)

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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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Lees, Professor Kennedy and Petrie, Professor Mark and Sattar, Professor Naveed
Authors: Anker, S. D., Butler, J., Filippatos, G. S., Jamal, W., Salsali, A., Schnee, J., Kimura, K., Zeller, C., George, J., Brueckmann, M., Zannad, F., Packer, M., Packer, M., Anker, S. D., Butler, J., Filippatos, G. S., Zannad, F., George, J., Brueckmann, M., Perrone, S., Nicholls, S., Janssens, S., Bocchi, E., Giannetti, N., Verma, S., Jian, Z., Gomez Mesa, J. E., Spinar, J., Böhm, M., Merkely, B., Chopra, V., Senni, M., Taddi, S., Tsutsui, H., Chuquiure, E., La Rocca, H. P. B., Ponikowski, P., Vinereanu, D., Sim, D., Choi, D.‐J., Juanatey, J. R. G., Squire, I., Butler, J., Januzzi, J., Pina, I., Pocock, S. J., Carson, P., Doehner, W., Miller, A., Haas, M., Pehrson, S., Komajda, M., Anand, I., Teerlink, J., Rabinstein, A., Steiner, T., Kamel, H., Tsivgoulis, G., Lewis, J., Freston, J., Kaplowitz, N., Mann, J., Petrie, M., Bernstein, R., Cheung, A., Green, J., Januzzi, J., Kaul, S., Ping, C. L. S., Lip, G., Marx, N., McCullough, P., Mehta, C., Ponikowski, P., Rosenstock, J., Sattar, N., Scirica, B., Tsutsui, H., Verma, S., Wanner, C., Welty, F. K., Parhofer, K. G., Clayton, T., Pedersen, T. R., Lees, K. R., Konstam, M. A., Greenberg, B., and Palmer, M.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
Journal Name:European Journal of Heart Failure
Publisher:Wiley
ISSN:1388-9842
ISSN (Online):1879-0844
Published Online:16 September 2019
Copyright Holders:Copyright © 2019 The Authors
First Published:First published in European Journal of Heart Failure 21(10):1279-1287
Publisher Policy:Reproduced under a Creative Commons license

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