Masanori Asakura1,2, Shin Ito2, Takahisa Yamada3, Yoshihiko Saito4, Kazuo Kimura5, Akira Yamashina6, Atsushi Hirayama7, Youichi Kobayashi8, Akihisa Hanatani9, Mitsuru Tsujimoto10, Satoshi Yasuda11, Yukio Abe12, Yorihiko Higashino13, Yodo Tamaki14, Hiroshi Sugino15, Hiroyuki Niinuma16, Yoshitaka Okuhara1, Toshimi Koitabashi17, Shin-Ichi Momomura18, Kuniya Asai19, Akihiro Nomura20, Hiroya Kawai21, Yasuhiro Satoh22, Tsutomu Yoshikawa23, Ken-Ichi Hirata24, Yoshiaki Yokoi25, Jun Tanaka26, Yoshisato Shibata27, Yasuhiro Maejima28, Shunsuke Tamaki3, Hiroyuki Kawata4, Noriaki Iwahashi5, Masatake Kobayashi6, Yoshiharu Higuchi7, Akiko Kada29, Haruko Yamamoto30, Masafumi Kitakaze2,31. 1. Department of Cardiovascular and Renal Medicine, Hyogo College of Medicine, Hyogo, Japan. 2. Department of Clinical Medicine and Development, National Cerebral and Cardiovascular Center, Osaka, Japan. 3. Division of Cardiology, Osaka General Medical Center, Osaka, Japan. 4. Department of Cardiovascular Medicine, Nara Medical University, Nara Medical University Hospital, Nara, Japan. 5. Division of Cardiology, Yokohama City University Medical Center, Yokohama, Japan. 6. Department of Cardiology, Tokyo Medical University, Tokyo, Japan. 7. The Division of Cardiology, Department of Medicine, Nihon University Itabashi Hospital, Tokyo, Japan. 8. Division of Cardiology, Department of Medicine, Showa University Hospital, Tokyo, Japan. 9. Department of Cardiovascular Medicine, Osaka City University Graduate School of Medicine, Osaka, Japan. 10. Department of Cardiology, Cardiovascular Center, Veritas Hospital, Hyogo, Japan. 11. Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Osaka, Japan. 12. Department of Cardiology, Osaka City General Hospital, Osaka, Japan. 13. Department of Cardiology, Higashi Takarazuka Satoh Hospital, Hyogo, Japan. 14. Department of Cardiology, Tenri Hospital, Nara, Tenri, Japan. 15. Department of Cardiac Surgery, National Hospital Organization Kure Medical Center and Chugoku Cancer Center, Hiroshima, Japan. 16. Department of Cardiology, St. Luke's International Hospital, Tokyo, Japan. 17. Department of Cardiovascular Medicine, Kitasato University School of Medicine, Tokyo, Japan. 18. Cardiovascular Division, Jichi Medical University Saitama Medical Center, Saitama, Japan. 19. Department of Cardiovascular Medicine, Nippon Medical School Chiba Hokusoh Hospital, Chiba, Japan. 20. Department of Cardiovascular and Internal Medicine, Kanazawa University Graduate School of Medical Science, Ishikawa, Japan. 21. Division of Cardiovascular Medicine, Hyogo Prefectural Himeji Cardiovascular Center, Hyogo Brain and Heart Center, Hyogo, Japan. 22. Department of Cardiology, National Hospital Organization Disaster Medical Center, Tokyo, Japan. 23. Department of Cardiology, Sakakibara Heart Institute, Tokyo, Japan. 24. Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan. 25. Department of Medicine, Cardiac Arrhythmia Center, Kishiwada Tokushukai Hospital, Kishiwada, Osaka, Japan. 26. Department of Cardiology, Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology, Tokyo, Japan. 27. Department of Cardiology, Miyazaki Medical Association Hospital, Miyazaki, Japan. 28. Department of Cardiovascular Medicine, Tokyo Medical and Dental University Medical Hospital, Tokyo, Japan. 29. Department of Clinical Research Management, National Hospital Organization Nagoya Medical Center, Aichi, Japan. 30. Department of Advance Medical Technology Development, National Cerebral and Cardiovascular Center, 6-1 Kishibeshinmachi Suita 564-8565, Osaka, Japan. 31. Hanwa Daini Senboku Hospital, 3176 Fukaikitamachi, Naka-ku Sakai City, Osaka 599-8271, Japan.
Abstract
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. Published on behalf of the European Society of Cardiology. All rights reserved.
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. Published on behalf of the European Society of Cardiology. All rights reserved.