title: Efficacy and Safety of 1-Hour Infusion of Recombinant Human Atrial Natriuretic Peptide in Patients With Acute Decompensated Heart Failure: A Phase III, Randomized, Double-Blind, Placebo-Controlled, Multicenter Trial.
abstract: The aim of the study was to evaluate the efficacy and safety of 1-h infusion of recombinant human atrial natriuretic peptide (rhANP) in combination with standard therapy in patients with acute decompensated heart failure (ADHF). This was a phase III, randomized, double-blind, placebo-controlled, multicenter trial. Eligible patients with ADHF were randomized to receive a 1-h infusion of either rhANP or placebo at a ratio of 3:1 in combination with standard therapy. The primary endpoint was dyspnea improvement (a decrease of at least 2 grades of dyspnea severity at 12 h from baseline). Reduction in pulmonary capillary wedge pressure (PCWP) 1 h after infusion was the co-primary endpoint for catheterized patients. Overall, 477 patients were randomized: 358 (93 catheterized) patients received rhANP and 118 (28 catheterized) received placebo. The percentage of patients with dyspnea improvement at 12 h was higher, although not statistically significant, in the rhANP group than in the placebo group (32.0% vs 25.4%, odds ratio=1.382, 95% confidence interval [CI]: 0.863-2.212, P = 0.17). Reduction in PCWP at 1 h was significantly greater in patients treated with rhANP than in patients treated with placebo (-7.74 ± 5.95 vs -1.82 ± 4.47 mm Hg, P < 0.001). The frequencies of adverse events and renal impairment within 3 days of treatment were similar between the 2 groups. Mortality at 1 month was 3.1% in the rhANP group vs 2.5% in the placebo group (hazard ratio = 1.21, 95% CI: 0.34-4.26; P > 0.99). 1-h rhANP infusion appears to result in prompt, transient hemodynamic improvement with a small, nonsignificant, effect on dyspnea in ADHF patients receiving standard therapy. The safety of 1-h infusion of rhANP seems to be acceptable. (WHO International Clinical Trials Registry Platform [ICTRP] number, ChiCTR-IPR-14005719.).
authors.affiliation: From the Department of Cardiology (G. Wang, P. Wang, J. Huang, H. Tan, J. Zhang, Z. Liao, L. Yu, Y. Mao, S. Ye, L. Feng, Y. Hua, X. Ni, Y. Zhang, X. Luan, X. Sun, S. Wang), Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College; Heart Center (P. Wang), First Hospital of Tsinghua University; Key Laboratory of Cardiovascular Drugs of Ministry of Health (Y. Li), Cardiovascular Institute and Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College; Department of Cardiology (W. Liu, S. Bai), Beijing Anzhen Hospital, The Capital University Medical Sciences, Beijing; Department of Cardiology (Y. Zhen), The First Hospital of Jilin University, Changchun; Department of Cardiology (D. Li), The Affiliated Hospital of Xuzhou Medical College, Xuzhou; Department of Cardiology (P. Yang, Y. Chen), China-Japan Friendship Hospital, Jilin University, Changchun; Department of Cardiology (LH), Jiangxi Provincial People's Hospital, Nanchang; Department of Cardiology (J. Sun), The First People's Hospital of Changzhou, Changzhou; Department of Cardiology (J. Chen), First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou; Department of Cardiology (X. Wang), Beijing Military General Hospital; Department of Cardiology (J. Zhu, D. Hu), Peking University People's Hospital, Beijing; Department of Cardiology (H. Li), The 254 Hospital of People's Liberation Army, Tianjin; Department of Cardiology (T. Wu), Guangzhou Red Cross Hospital, Guangzhou; and Medical Research & Biometrics Center (Y. Wang, W. Li), National Center for Cardiovascular Diseases, Beijing, China.
authors.forename: Guogan
authors.initials: G
authors.lastname: Wang
authors.forename: Pengbo
authors.initials: P
authors.lastname: Wang
authors.forename: Yishi
authors.initials: Y
authors.lastname: Li
authors.forename: Wenxian
authors.initials: W
authors.lastname: Liu
authors.forename: Shugong
authors.initials: S
authors.lastname: Bai
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhen
authors.forename: Dongye
authors.initials: D
authors.lastname: Li
authors.forename: Ping
authors.initials: P
authors.lastname: Yang
authors.forename: Yu
authors.initials: Y
authors.lastname: Chen
authors.forename: Lang
authors.initials: L
authors.lastname: Hong
authors.forename: Jianhui
authors.initials: J
authors.lastname: Sun
authors.forename: Junzhu
authors.initials: J
authors.lastname: Chen
authors.forename: Xian
authors.initials: X
authors.lastname: Wang
authors.forename: Jihong
authors.initials: J
authors.lastname: Zhu
authors.forename: Dayi
authors.initials: D
authors.lastname: Hu
authors.forename: Huimin
authors.initials: H
authors.lastname: Li
authors.forename: Tongguo
authors.initials: T
authors.lastname: Wu
authors.forename: Jie
authors.initials: J
authors.lastname: Huang
authors.forename: Huiqiong
authors.initials: H
authors.lastname: Tan
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.forename: Zhongkai
authors.initials: Z
authors.lastname: Liao
authors.forename: Litian
authors.initials: L
authors.lastname: Yu
authors.forename: Yi
authors.initials: Y
authors.lastname: Mao
authors.forename: Shaodong
authors.initials: S
authors.lastname: Ye
authors.forename: Lei
authors.initials: L
authors.lastname: Feng
authors.forename: Yihong
authors.initials: Y
authors.lastname: Hua
authors.forename: Xinhai
authors.initials: X
authors.lastname: Ni
authors.forename: Yuhui
authors.initials: Y
authors.lastname: Zhang
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Luan
authors.forename: Xiaolu
authors.initials: X
authors.lastname: Sun
authors.forename: Sijia
authors.initials: S
authors.lastname: Wang
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D009320:Atrial Natriuretic Factor / Q000627:therapeutic use*; D002317:Cardiovascular Agents / Q000627:therapeutic use*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006333:Heart Failure / Q000188:drug therapy*; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome
chemical_list: D002317:Cardiovascular Agents; D009320:Atrial Natriuretic Factor