Efficacy and Safety of Early Initiation of Eplerenone Treatment in Patients with Acute Heart Failure (EARLIER trial): a multicentre, randomized, double-blind, placebo-controlled trial

被引：24

作者：

Asakura, Masanori ^{[1
,2
]}

Ito, Shin ^{[2
]}

Yamada, Takahisa ^{[3
]}

Saito, Yoshihiko ^{[4
]}

Kimura, Kazuo ^{[5
]}

Yamashina, Akira ^{[6
]}

Hirayama, Atsushi ^{[7
,34
]}

Kobayashi, Youichi ^{[8
]}

Hanatani, Akihisa ^{[9
,34
]}

Tsujimoto, Mitsuru ^{[10
]}

Yasuda, Satoshi ^{[11
]}

Abe, Yukio ^{[12
]}

Higashino, Yorihiko ^{[13
,34
]}

Tamaki, Yodo ^{[14
]}

Sugino, Hiroshi ^{[15
,16
]}

Niinuma, Hiroyuki ^{[17
]}

Okuhara, Yoshitaka ^{[1
]}

Koitabashi, Toshimi ^{[18
]}

Momomura, Shin-Ichi ^{[19
]}

Asai, Kuniya ^{[20
]}

Nomura, Akihiro ^{[21
]}

Kawai, Hiroya ^{[22
,35
]}

Satoh, Yasuhiro ^{[23
]}

Yoshikawa, Tsutomu ^{[24
]}

Hirata, Ken-Ichi ^{[25
]}

Yokoi, Yoshiaki ^{[26
]}

Tanaka, Jun ^{[27
,28
]}

Shibata, Yoshisato ^{[29
]}

Maejima, Yasuhiro ^{[30
]}

Tamaki, Shunsuke ^{[3
]}

Kawata, Hiroyuki ^{[4
,35
]}

Iwahashi, Noriaki ^{[5
]}

Kobayashi, Masatake ^{[6
]}

Higuchi, Yoshiharu ^{[7
,34
]}

Kada, Akiko ^{[31
]}

Yamamoto, Haruko ^{[32
]}

Kitakaze, Masafumi ^{[2
,33
]}

机构：

[1] Hyogo Coll Med, Dept Cardiovasc & Renal Med, Nishinomiya, Hyogo, Japan

[2] Natl Cerebral & Cardiovasc Ctr, Dept Clin Med & Dev, Osaka, Japan

[3] Osaka Gen Med Ctr, Div Cardiol, Osaka, Japan

[4] Nara Med Univ, Nara Med Univ Hosp, Dept Cardiovasc Med, Nara, Japan

[5] Yokohama City Univ, Med Ctr, Div Cardiol, Yokohama, Kanagawa, Japan

[6] Tokyo Med Univ, Dept Cardiol, Tokyo, Japan

[7] Nihon Univ, Itabashi Hosp, Dept Med, Div Cardiol, Tokyo, Japan

[8] Showa Univ Hosp, Dept Med, Div Cardiol, Tokyo, Japan

[9] Osaka City Univ, Grad Sch Med, Dept Cardiovasc Med, Osaka, Japan

[10] Veritas Hosp, Cardiovasc Ctr, Dept Cardiol, Kawanishi, Hyogo, Japan

[11] Natl Cerebral & Cardiovasc Ctr, Dept Cardiovasc Med, Osaka, Japan

[12] Osaka City Gen Hosp, Dept Cardiol, Osaka, Japan

[13] Higashi Takarazuka Satoh Hosp, Dept Cardiol, Takarazuka, Hyogo, Japan

[14] Tenri Hosp, Dept Cardiol, Tenri, Nara, Japan

[15] Natl Hosp Org Kure Med Ctr, Dept Cardiac Surg, Hiroshima, Japan

[16] Chugoku Canc Ctr, Hiroshima, Japan

[17] St Lukes Int Hosp, Dept Cardiol, Tokyo, Japan

[18] Kitasato Univ, Sch Med, Dept Cardiovasc Med, Tokyo, Japan

[19] Jichi Med Univ, Saitama Med Ctr, Cardiovasc Div, Saitama, Japan

[20] Chiba Hokusoh Hosp, Nippon Med Sch, Dept Cardiovasc Med, Chiba, Japan

[21] Kanazawa Univ, Grad Sch Med Sci, Dept Cardiovasc & Internal Med, Kanazawa, Ishikawa, Japan

[22] Hyogo Brain & Heart Ctr, Hyogo Prefectural Himeji Cardiovasc Ctr, Div Cardiovasc Med, Himeji, Hyogo, Japan

[23] Natl Hosp Org Disaster Med Ctr, Dept Cardiol, Tokyo, Japan

[24] Sakakibara Heart Inst, Dept Cardiol, Tokyo, Japan

[25] Kobe Univ, Grad Sch Med, Dept Internal Med, Div Cardiovasc Med, Kobe, Hyogo, Japan

[26] Kishiwada Tokushukai Hosp, Cardiac Arrhythmia Ctr, Dept Med, Kishiwada, Osaka, Japan

[27] Tokyo Metropolitan Geriatr Hosp, Dept Cardiol, Tokyo, Japan

[28] Inst Gerontol, Tokyo, Japan

[29] Miyazaki Med Assoc Hosp, Dept Cardiol, Miyazaki, Japan

[30] Tokyo Med & Dent Univ, Med Hosp, Dept Cardiovasc Med, Tokyo, Japan

[31] Natl Hosp Org Nagoya Med Ctr, Dept Clin Res Management, Nagoya, Aichi, Japan

[32] Natl Cerebral & Cardiovasc Ctr, Dept Adv Med Technol Dev, 6-1 Kishibeshinmachi, Suita, Osaka 5648565, Japan

[33] Hanwa Daini Senboku Hosp, Naka Ku, 3176 Fukaikitamachi, Sakai, Osaka 5998271, Japan

[34] Osaka Police Hosp, Osaka, Japan

[35] Nara Prefectural Gen Med Ctr, Nara, Japan

来源：

EUROPEAN HEART JOURNAL-CARDIOVASCULAR PHARMACOTHERAPY | 2022年 / 8卷 / 02期

关键词：

Mineralocorticoid receptor antagonist; Acute heart failure; Eplerenone; ANGIOTENSIN-ALDOSTERONE SYSTEM; MYOCARDIAL-INFARCTION; MORTALITY; HOSPITALIZATION; SPIRONOLACTONE; DYSFUNCTION; GUIDELINES; EMPHASIS; OUTCOMES; BLOCKER;

D O I：

10.1093/ehjcvp/pvaa132

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Aims A mineralocorticoid receptor antagonist (MRA) is effective in patients with chronic heart failure; however, the effects of the early initiation of an MRA in patients with acute heart failure (AHF) have not been elucidated. Methods and results In this multicentre, randomized, double-blind, placebo-controlled, parallel-group study, we focused on the safety and effectiveness of the treatment with eplerenone, a selective MRA in 300 patients with AHF, that is, 149 in the eplerenone group and 151 in the placebo group in 27 Japanese institutions. The key inclusion criteria were (i) patients aged 20 years or older and (ii) those with left ventricular ejection fraction of <= 40%. The primary outcome was a composite of cardiac death or first re-hospitalization due to cardiovascular disease within 6 months. The mean age of the participants was 66.8 years, 27.3% were women, and the median levels of brain natriuretic peptide were 376.0 pg/mL. The incidences of the primary outcome were 19.5% in the eplerenone group and 17.2% in the placebo group [hazard ratio (HR): 1.09, 95% confidence interval (CI): 0.642-1.855]. In prespecified secondary outcomes, HR for the composite endpoint, cardiovascular death, or first re-hospitalization due to heart failure within 6 months was 0.55 (95% CI: 0.213-1.434). The safety profile for eplerenone was as expected. Conclusion The early initiation of eplerenone in patients with AHF could safely be utilized. The reduction of the incidence of a composite of cardiovascular death or first re-hospitalization for cardiovascular diseases by eplerenone is inconclusive because of inadequate power.

引用

页码：108 / 117

页数：10

共 27 条

[1] In-hospital mortality in patients with acute decompensated heart failure requiring intravenous vasoactive medications - An analysis from the Acute Decompensated Heart Failure National Registry (ADHERE) [J].

Abraham, WT ;

Adams, KF ;

Fonarow, GC ;

Costanzo, MR ;

Berkowitz, RL ;

LeJemtel, TH ;

Cheng, ML ;

Wynne, J .

JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 2005, 46 (01) :57-64

[2] Timing of eplerenone initiation and outcomes in patients with heart failure after acute myocardial infarction complicated by left ventricular systolic dysfunction: insights from the EPHESUS trial [J].

Adamopoulos, Chris ;

Ahmed, Ali ;

Fay, Renaud ;

Angioi, Michael ;

Filippatos, Gerasimos ;

Vincent, John ;

Pitt, Bertram ;

Zannad, Faiez .

EUROPEAN JOURNAL OF HEART FAILURE, 2009, 11 (11) :1099-1105

[3] Rationale and Design of the Double-Blind, Randomized, Placebo-Controlled Multicenter Trial on Efficacy of Early Initiation of Eplerenone Treatment in Patients with Acute Heart Failure (EARLIER) [J].

Asakura, Masanori ;

Yamamoto, Haruko ;

Asai, Kuniya ;

Hanatani, Akihisa ;

Hirata, Ken-ichi ;

Hirayakma, Atsushi ;

Kimura, Kazuo ;

Kobayashi, Youichi ;

Momomura, Shin-ichi ;

Nakagawa, Yoshihisa ;

Nishi, Yutaro ;

Saito, Yoshihiko ;

Satoh, Yasuhiro ;

Yamada, Takahisa ;

Yamashina, Akira ;

Yasuda, Satoshi ;

Yoshikawa, Tsutomu ;

Kada, Akiko ;

Uesaka, Hiroyuki ;

Kitakaze, Masafumi .

CARDIOVASCULAR DRUGS AND THERAPY, 2015, 29 (02) :179-185

[4] Eplerenone - Cardiovascular protection [J].

Brown, NJ .

CIRCULATION, 2003, 107 (19) :2512-2518

[5] Efficacy and Safety of Spironolactone in Acute Heart Failure The ATHENA-HF Randomized Clinical Trial [J].

Butler, Javed ;

Anstrom, Kevin J. ;

Felker, G. Michael ;

Givertz, Michael M. ;

Kalogeropoulos, Andreas P. ;

Konstam, Marvin A. ;

Mann, Douglas L. ;

Margulies, Kenneth B. ;

McNulty, Steven E. ;

Mentz, Robert J. ;

Redfield, Margaret M. ;

Tang, W. H. Wilson ;

Whellan, David J. ;

Shah, Monica ;

Desvigne-Nickens, Patrice ;

Hernandez, Adrian F. ;

Braunwald, Eugene .

JAMA CARDIOLOGY, 2017, 2 (09) :950-958

[6] Incidence and Survival of Hospitalized Acute Decompensated Heart Failure in Four US Communities (from the Atherosclerosis Risk in Communities Study) [J].

Chang, Patricia P. ;

Chambless, Lloyd E. ;

Shahar, Eyal ;

Bertoni, Alain G. ;

Russell, Stuart D. ;

Ni, Hanyu ;

He, Max ;

Mosley, Thomas H. ;

Wagenknecht, Lynne E. ;

Samdarshi, Tandaw E. ;

Wruck, Lisa M. ;

Rosamond, Wayne D. .

AMERICAN JOURNAL OF CARDIOLOGY, 2014, 113 (03) :504-510

[7] Overview of acutely decompensated congestive heart failure (ADHF): A report from the ADHERE Registry [J].

Fonarow, GC .

HEART FAILURE REVIEWS, 2004, 9 (03) :179-185

[8] A comprehensive, longitudinal description of the in-hospital and post-discharge clinical, laboratory, and neurohormonal course of patients with heart failure who die or are re-hospitalized within 90 days: analysis from the EVEREST trial [J].

Gheorghiade, Mihai ;

Pang, Peter S. ;

Ambrosy, Andrew P. ;

Lan, Gloria ;

Schmidt, Philip ;

Filippatos, Gerasimos ;

Konstam, Marvin ;

Swedberg, Karl ;

Cook, Thomas ;

Traver, Brian ;

Maggioni, Aldo ;

Burnett, John ;

Grinfeld, Liliana ;

Udelson, James ;

Zannad, Faiez .

HEART FAILURE REVIEWS, 2012, 17 (03) :485-509

[9] Serum aldosterone is associated with mortality and re-hospitalization in patients with reduced ejection fraction hospitalized for acute heart failure: analysis from the EVEREST trial [J].

Girerd, Nicolas ;

Pang, Peter S. ;

Swedberg, Karl ;

Fought, Angela ;

Kwasny, Mary J. ;

Subacius, Haris ;

Konstam, Marvin A. ;

Maggioni, Aldo ;

Gheorghiade, Mihai ;

Zannad, Faiez .

EUROPEAN JOURNAL OF HEART FAILURE, 2013, 15 (11) :1228-1235

[10] Guidelines for Treatment of Acute Heart Failure (JCS 2011) - Digest Version [J].

Izumi, Tohru ;

Hirayama, Atsushi ;

Isobe, Mitsuaki ;

Ito, Hiroshi ;

Kitakaze, Masafumi ;

Momomura, Shin-ichi ;

Sawa, Yoshiki ;

Seino, Yoshihiko ;

Tsutsui, Hiroyuki ;

Yamazaki, Kenji ;

Yoshikawa, Tsutomu ;

Adachi, Hitoshi ;

Anzai, Toshihisa ;

Aoyama, Naoyoshi ;

Goto, Yoichi ;

Hashimura, Kazuhiko ;

Inomata, Takayuki ;

Kato, Mahoto ;

Kinugawa, Shintaro ;

Nakamura, Kazufumi ;

Nishigaki, Kazuhiko ;

Niwano, Shinichi ;

Onishi, Katsuya ;

Ozawa, Taketoshi ;

Sakata, Yasushi ;

Sato, Naoki ;

Sato, Yukihito ;

Kato, Tomoko Sugiyama ;

Tsuchihashi-Makaya, Miyuki ;

Yamamoto, Kazuhiro ;

Yasumura, Yoshio ;

Yokoyama, Hiroyuki ;

Hori, Masatsugu ;

Imaizumi, Tsutomu ;

Nakatani, Takeshi ;

Saku, Keijiro ;

Yoshimura, Michihiro .

CIRCULATION JOURNAL, 2013, 77 (08) :2157-2201

← 1 2 3 →