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

被引：141

作者：

Packer, Milton ^{[1
,2
,16
]}

Butler, Javed ^{[3
,17
,43
]}

Filippatos, Gerasimos S. ^{[4
,5
,18
]}

Jamal, Waheed ^{[6
]}

Salsali, Afshin ^{[7
]}

Schnee, Janet ^{[7
]}

Kimura, Karen ^{[8
]}

Zeller, Cordula ^{[9
]}

George, Jyothis ^{[6
,20
]}

Brueckmann, Martina ^{[6
,10
,20
]}

Anker, Stefan D. ^{[11
,12
,13
,14
]}

Zannad, Faiez ^{[13
,14
,15
,19
]}

Perrone, Sergio ^{[21
]}

Nicholls, Stephen ^{[22
]}

Janssens, Stefan ^{[23
]}

Bocchi, Edmar ^{[24
]}

Giannetti, Nadia ^{[25
]}

Verma, Subodh ^{[26
,80
]}

Jian, Zhang ^{[27
]}

Spinar, Jindrich ^{[28
]}

Seronde, Marie-France ^{[29
]}

Boehm, Michael ^{[30
,31
]}

Merkely, Bela ^{[32
]}

Chopra, Vijay ^{[33
]}

Senni, Michele ^{[34
]}

Taddei, Stefano ^{[35
]}

Tsutsui, Hiroyuki ^{[36
,79
]}

Choi, Dong-Ju ^{[37
]}

Chuquiure, Eduardo ^{[38
]}

La Rocca, Hans Pieter Brunner ^{[39
]}

Ponikowski, Piotr ^{[40
,75
]}

Gonzalez Juanatey, Jose Ramon ^{[41
]}

Squire, Iain ^{[42
]}

Januzzi, James ^{[44
,68
]}

Pina, Ileana ^{[45
]}

Pocock, Stuart J. ^{[46
]}

Carson, Peter ^{[47
]}

Doehner, Wolfram ^{[48
]}

Miller, Alan ^{[49
]}

Haas, Markus ^{[50
]}

Pehrson, Steen ^{[51
]}

Komajda, Michel ^{[52
]}

Anand, Inder ^{[53
,54
]}

Teerlink, John ^{[55
]}

Rabinstein, Alejandro ^{[56
]}

Steiner, Thorsten ^{[57
]}

Kamel, Hooman ^{[58
]}

Tsivgoulis, Georgios ^{[59
]}

Lewis, James ^{[60
]}

Freston, James ^{[61
]}

机构：

[1] Baylor Univ, Med Ctr, Baylor Heart & Vasc Inst, Dallas, TX USA

[2] Imperial Coll, London, England

[3] Univ Mississippi, Sch Med, Jackson, MI USA

[4] Natl & Kapodistrian Univ Athens, Dept Cardiol, Athens, Greece

[5] Athens Univ Hosp Attikon, Sch Med, Athens, Greece

[6] Boehringer Ingelheim Int GmbH, Ingelheim, Germany

[7] Boehringer Ingelheim Pharmaceut, Ridgefield, CT USA

[8] Boehringer Ingelheim Canada Ltd, Burlington, ON, Canada

[9] Boehringer Ingelheim Pharma GmbH & Co KG, Biberach, Germany

[10] Heidelberg Univ, Fac Med Mannheim, Mannheim, Germany

[11] Dept Cardiol CVK, Berlin, Germany

[12] Berlin Inst Hlth Ctr Regenerat Therapies BCRT, Berlin, Germany

[13] German Ctr Cardiovasc Res DZHK Partner Site, Berlin, Germany

[14] German Ctr Cardiovasc Res DZHK Partner Site, Berlin, Germany

[15] Univ Lorraine, CHRU, INSERM, INI CRCT, Nancy, France

[16] Baylor Univ, Med Ctr, Dallas, TX USA

[17] Univ Mississippi, Jackson, MI USA

[18] Natl & Kapodistrian Univ Athens, Sch Med, Athens, Greece

[19] Univ Lorraine, INSERM, CHRU, INI CRCT, Nancy, France

[20] Boehringer Ingelheim Int, Ingelheim, Germany

[21] FLENI Fdn, Dept Cardiol, Buenos Aires, DF, Argentina

[22] Monash Univ, Clayton, Vic, Australia

[23] Univ Ziekenhuis Leuven, Leuven, Belgium

[24] Univ Sao Paulo, Sch Med, Sao Paulo, Brazil

[25] Ctr Univ Sante McGill, Montreal, PQ, Canada

[26] Univ Toronto, St Michaels Hosp, Toronto, ON, Canada

[27] Chinese Acad Med Sci, Fuwai Hosp, Beijing, Peoples R China

[28] Masaryk Univ Hosp, Univ Hosp, Brno, Czech Republic

[29] Ctr Hosp Reg & Univ Besancon, Besancon, France

[30] Univ Klinikum Saarlandes, Homberg, Germany

[31] Univ Saarland, Fak Med, Homberg, Germany

[32] Semmelweis Univ, Budapest, Hungary

[33] Medanta The Medicity, Gurugram, India

[34] ASST Papa Giovanni XXIII, Bergamo, Italy

[35] Azienda Osped Univ Pisana, Pisa, Italy

[36] Kyushu Univ, Fukuoka, Fukuoka, Japan

[37] Seoul Natl Univ, Bundang Hosp, Seoul, South Korea

[38] Inst Nacl Cardiol Dr Ignacio Chavez Riera, Mexico City, DF, Mexico

[39] Maastricht Univ, Med Ctr, Maastricht, Netherlands

[40] Wroclaw Med Univ, Wroclaw, Poland

[41] Complejo Hosp Univ Santiago, La Coruna, Spain

[42] Glenfield Hosp, Leicester, Leics, England

[43] Univ Mississippi, Jackson, MI USA

[44] Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA 02115 USA

[45] DMC Specialty Ctr Heart Hosp, Detroit, MI USA

[46] London Sch Hyg & Trop Med, London, England

[47] Vet Affairs Med Ctr Washington, Washington, DC USA

[48] Charite Univ Med Berlin, Berlin, Germany

[49] Univ Florida Hlth, Jacksonville, FL USA

[50] Theresienkrankenhaus, Mannheim, Germany

来源：

EUROPEAN JOURNAL OF HEART FAILURE | 2019年 / 21卷 / 10期

关键词：

Heart failure; Diabetes; Reduced ejection fraction; SGLT2; inhibitors; Trial design; NA+/H+-EXCHANGER; SGLT2; INHIBITORS; OUTCOMES; HOSPITALIZATION; MECHANISM; RISK;

D O I：

10.1002/ejhf.1536

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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 approximate to 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 approximate to 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.

引用

页码：1270 / 1278

页数：9

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