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
Masanori Asakura, Shin Ito, Takahisa Yamada, Yoshihiko Saito, Kazuo Kimura, Akira Yamashina, Atsushi Hirayama, Youichi Kobayashi, Akihisa Hanatani, Mitsuru Tsujimoto, Satoshi Yasuda, Yukio Abe, Yorihiko Higashino, Yodo Tamaki, Hiroshi Sugino, Hiroyuki Niinuma, Yoshitaka Okuhara, Toshimi Koitabashi, Shin‐ichi Momomura, Kuniya Asai, Akihiro Nomura, Hiroya Kawai, Yasuhiro Satoh, Tsutomu Yoshikawa, Ken–ichi Hirata, Yoshiaki Yokoi, Jun Tanaka, Yoshisato Shibata, Yasuhiro Maejima, Shunsuke Tamaki, Hiroyuki Kawata, Noriaki Iwahashi, Masatake Kobayashi, Yoshiharu Higuchi, Akiko Kada, Haruko Yamamoto, Masafumi Kitakaze
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.