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. (16th September 2019)

• Record Type: Journal Article
• Authors: Anker, Stefan D.; Butler, Javed; Filippatos, Gerasimos S.; Jamal, Waheed; Salsali, Afshin; Schnee, Janet; Kimura, Karen; Zeller, Cordula; George, Jyothis; Brueckmann, Martina; Zannad, Faiez; Packer, Milton
• Other Names: Packer Milton investigator.; Anker Stefan D. investigator.; Butler Javed investigator.; Filippatos Gerasimos S. investigator.; Zannad Faiez investigator.; George Jyothis investigator.; Brueckmann Martina investigator.; Perrone Sergio investigator.; Nicholls Stephen investigator.; Janssens Stefan investigator.; Bocchi Edmar investigator.; Giannetti Nadia investigator.; Verma Subodh investigator.; Jian Zhang investigator.; Gomez Mesa Juan Esteban investigator.; Spinar Jindrich investigator.; Böhm Michael investigator.; Merkely Bela investigator.; Chopra Vijay investigator.; Senni Michele investigator.; Taddi Stefano investigator.; Tsutsui Hiroyuki investigator.; Chuquiure Eduardo investigator.; La Rocca Hans Pieter Brunner investigator.; Ponikowski Piotr investigator.; Vinereanu Dragos investigator.; Sim David investigator.; Choi Dong‐Ju investigator.; Juanatey Jose Ramon Gonzalez investigator.; Squire Iain investigator.; Butler Javed investigator.; Januzzi James investigator.; Pina Ileana investigator.; Pocock Stuart J. investigator.; Carson Peter investigator.; Doehner Wolfram investigator.; Miller Alan investigator.; Haas Markus investigator.; Pehrson Steen investigator.; Komajda Michel investigator.; Anand Inder investigator.; Teerlink John investigator.; Rabinstein Alejandro investigator.; Steiner Thorsten investigator.; Kamel Hooman investigator.; Tsivgoulis Georgios investigator.; Lewis James investigator.; Freston James investigator.; Kaplowitz Neil investigator.; Mann Johannes investigator.; Petrie Mark investigator.; Bernstein Richard investigator.; Cheung Alfred investigator.; Green Jennifer investigator.; Januzzi James investigator.; Kaul Sanjay investigator.; Ping Carolyn Lam Su investigator.; Lip Gregory investigator.; Marx Nikolaus investigator.; McCullough Peter investigator.; Mehta Cyrus investigator.; Ponikowski Piotr investigator.; Rosenstock Julio investigator.; Sattar Naveed investigator.; Scirica Benjamin investigator.; Tsutsui Hiroyuki investigator.; Verma Subodh investigator.; Wanner Christoph investigator.; Welty Francine K. investigator.; Parhofer Klaus G. investigator.; Clayton Tim investigator.; Pedersen Terje R. investigator.; Lees Kennedy R. investigator.; Konstam Marvin A. investigator.; Greenberg Barry investigator.; Palmer Mike investigator.;
• Is Part Of: European journal of heart failure. Volume 21:Number 10(2019)
• Page Start: 1279
• Page End: 1287
• Publication Date: 2019-09-16
• Subjects: Heart failure -- Diabetes -- SGLT2 inhibitors -- Trial design; Heart failure -- Periodicals; Heart Failure -- Periodicals; Insuffisance cardiaque -- Périodiques; Heart failure; Periodicals; 616.129005
• DOI: 10.1002/ejhf.1596
• Languages: English
• ISSNs: 1388-9842

Abstract

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.