Stefan D Anker1, Javed Butler2, Gerasimos S Filippatos3,4, Waheed Jamal5, Afshin Salsali6, Janet Schnee6, Karen Kimura7, Cordula Zeller8, Jyothis George5, Martina Brueckmann5,9, Faiez Zannad10, Milton Packer11,12. 1. Department of Cardiology (CVK) and Berlin Institute of Health Centre for Regenerative Therapies (BCRT), German Centre for Cardiovascular Research (DZHK) Partner Site, Berlin, Germany. 2. University of Mississippi School of Medicine, Jackson, MI, USA. 3. School of Medicine, National and Kapodistrian University of Athens, Athens University Hospital Attikon, Athens, Greece. 4. School of Medicine, University of Cyprus, Nicosia, Cyprus. 5. Boehringer Ingelheim International GmbH, Ingelheim, Germany. 6. Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, USA. 7. Boehringer Ingelheim Canada Ltd, Burlington, ON, Canada. 8. Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany. 9. Faculty of Medicine Mannheim, University of Heidelberg, Mannheim, Germany. 10. Inserm INI-CRCT, CHRU, University of Lorraine, Nancy, France. 11. Baylor Heart and Vascular Institute, Baylor University Medical Center, Dallas, TX, USA. 12. Imperial College, London, UK.
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.
RCT Entities:
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.
Authors: Agnieszka Kapłon-Cieślicka; Karolina Kupczyńska; Piotr Dobrowolski; Błażej Michalski; Miłosz J Jaguszewski; Waldemar Banasiak; Paweł Burchardt; Łukasz Chrzanowski; Szymon Darocha; Justyna Domienik-Karłowicz; Jarosław Drożdż; Marcin Fijałkowski; Krzysztof J Filipiak; Marcin Gruchała; Ewa A Jankowska; Piotr Jankowski; Jarosław D Kasprzak; Wojciech Kosmala; Piotr Lipiec; Przemysław Mitkowski; Katarzyna Mizia-Stec; Piotr Szymański; Agnieszka Tycińska; Wojciech Wańha; Maciej Wybraniec; Adam Witkowski; Piotr Ponikowski; On Behalf Of "Club 30" Of The Polish Cardiac Society Journal: Cardiol J Date: 2020-09-28 Impact factor: 2.737
Authors: Ravi B Patel; Jozine M Ter Maaten; João Pedro Ferreira; Finnian R McCausland; Sanjiv J Shah; Patrick Rossignol; Scott D Solomon; Muthiah Vaduganathan; Milton Packer; Aliza Thompson; Norman Stockbridge; Faiez Zannad Journal: Circulation Date: 2021-01-07 Impact factor: 29.690
Authors: Marc Evans; Angharad R Morgan; Zaheer Yousef; Gethin Ellis; Umesh Dashora; Dipesh C Patel; Pam Brown; Wasim Hanif; Johnathan N Townend; Naresh Kanumilli; Jim Moore; John P H Wilding; Stephen C Bain Journal: Drugs Date: 2021-06-23 Impact factor: 9.546