重组人脑利钠肽治疗心力衰竭安全性和疗效的开放性随机对照多中心临床研究

Efficacy and safety of intravenous recombinant human brain natriuretic peptide in patients with decompensated acute heart failure： a multicenter, randomized, open label, controlled study

目的 观察重组人脑利钠肽在广泛使用条件下治疗心力衰竭（心衰）的安全性,并对比不同给药剂量和给药时间的疗效差异.方法对入选的2160例急性心衰和慢性心衰急性发作患者采用多中心、随机、开放、剂量对照的方法进行采集和统计分析.入选患者随机分为四个不同剂量和给药时间组,同时均给予标准治疗.结果安全性方面,全部患者低血压发生率为1.44%;肌酐在治疗后5～7 d和基线比较时,0.015μg、24 h治疗前后差异无统计学意义（P=0.7054）,其他三组肌酐有所改善（P值分别为0.0437、0.0087、0.0116）;30 d内再住院率5.65%,病死率9.44%.疗效方面,与基线相比,各组均有明显的呼吸困难改善（P＜0.01）;给药后利尿量增加了76.59%（P＜0.01）,左室射血分数增加了12.08%（P值分别为0.0035、0.0001、0、0.0012）;给药5～7 d,N末端B型利钠肽原降低40.29%（P＜0.01）.结论临床应用重组人脑利钠肽治疗心衰的不良事件发生率低,能明显改善患者呼吸困难程度,降低N末端B型利钠肽原,改善左室射血分数.

Objective To explore the safety of intravenous recombinant human brain natriuretic peptide （rhBNP） in treating acute decompensated heart failure and acute exacerbation of chronic heart failure, and to compare the differences in efficacy with different dosage and administration time. Methods A total of 2160 patients characterized of acute decompensated heart failure and acute exacerbation of chronic heart failure were enrolled in this multicenter, randomized, open, dose-control study. The patients were randomly allocated to four groups with different doses and administration time on top of standard therapy. Results In the safety respect, the rate of hypotension is 1.44% at 5 -7 days after treatment, the serum creatinine level was reduced compared to baseline（ P values were 0. 0437, 0. 0087 and 0. 0116）except in the group of 0. 015 μg at 24 h （P =0. 7054）. The rate of 30-day readmission is 5.65%, mortality rate is 9. 44%. In terms of efficacy, dyspnea was significantly improved at 30 min after administration, and at 24 h after administration （ all P 〈 0. 01 ）. Urine output and LEVF were also significantly increased by 76. 59% （P 〈0. 01 ） and 12. 08% respectively （ all P 〈 0. 01 ） compared to baseline. Plasma NT-proBNP decreased by 40. 29% at 5 - 7 days after administration （ P 〈 0. 01 ）. Conclusion The clinical application of intravenous rhBNP is safe and effective for treatment of acute decompensated heart failure and acute exacerbation of chronic heart failure in this large patient cohort.