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. (16th July 2019)

• Record Type: Journal Article
• Authors: Packer, Milton; Butler, Javed; Filippatos, Gerasimos S.; Jamal, Waheed; Salsali, Afshin; Schnee, Janet; Kimura, Karen; Zeller, Cordula; George, Jyothis; Brueckmann, Martina; Anker, Stefan D.; Zannad, Faiez
• Other Names: investigator.; Packer Milton investigator.; Anker Stefan D. investigator.; Butler Javed investigator.; Filippatos Gerasimos investigator.; Zannad Faiez investigator.; George Jyothis investigator.; Brueckmann Martina investigator.; investigator.; Perrone Sergio investigator.; Nicholls Stephen investigator.; Janssens Stefan investigator.; Bocchi Edmar investigator.; Giannetti Nadia investigator.; Verma Subodh investigator.; Jian Zhang investigator.; Spinar Jindrich investigator.; Seronde Marie‐France investigator.; Böhm Michael investigator.; Merkely Bela investigator.; Chopra Vijay investigator.; Senni Michele investigator.; Taddei Stefano investigator.; Tsutsui Hiroyuki investigator.; Choi Dong‐Ju investigator.; Chuquiure Eduardo investigator.; La Rocca Hans Pieter Brunner investigator.; Ponikowski Piotr investigator.; Juanatey Jose Ramon Gonzalez investigator.; Squire Iain investigator.; Butler Javed investigator.; Januzzi James investigator.; Pina Ileana investigator.; investigator.; Pocock Stuart J. investigator.; 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.; 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.; 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: 1270
• Page End: 1278
• Publication Date: 2019-07-16
• Subjects: Heart failure -- Diabetes -- Reduced ejection fraction -- SGLT2 inhibitors -- Trial design; Heart failure -- Periodicals; Heart Failure -- Periodicals; Insuffisance cardiaque -- Périodiques; Heart failure; Periodicals; 616.129005
• DOI: 10.1002/ejhf.1536
• Languages: English
• ISSNs: 1388-9842

Abstract

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.