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托伐普坦附加疗法对急性心力衰竭患者的影响:随机对照试验的荟萃分析

Effects of tolvaptan add-on therapy in patients with acute heart failure: meta-analysis on randomised controlled trials.

作者信息

Ma Guang, Ma Xixi, Wang Guoliang, Teng Wei, Hui Xuezhi

机构信息

The First Affiliated Hospital of Henan University, Kaifeng, China.

出版信息

BMJ Open. 2019 May 1;9(4):e025537. doi: 10.1136/bmjopen-2018-025537.

Abstract

OBJECTIVES

Treating acute decompensated heartfailure (ADHF) for improving congestion with diuretics may cause worsening renal function (WRF), but the clinical efficacy of tolvaptan add-on therapy on reducing WRF in ADHF patients is inconsistent. This analysis is to evaluate the effects of tolvaptan add-on therapy on reducing WRF in ADHF patients.

METHODS

Meta-analysis of randomised trials of tolvaptan add-on therapy on reducing WRF in ADHF patients. The MEDLINE, Embase and Cochrane Central Register of Controlled Trials databases were searched for relevant articles from their inception to 31 October, 2017. Two reviewers filtrated the documents on WRF, short-term all-cause mortality, body weight decreased, elevated sodium level for calculating pooled relatives risks, weighted mean difference and associated 95% CIs. We used fixed-effects or random-effects models according to I statistics.

ACHIEVEMENTS

Seven random controlled trials with 937 patients were included for analysis. Compared with the control, tolvaptan add-on therapy did not improve incidence of worsening renal function (RR 0.78, 95% CI 0.48 to 1.26, p=0.31, I=66%) and short-term all-cause mortality (RR 0.85, 95% CI 0.47 to 1.56, p=0.61, I=0%). On subgroup analyses, there was a suggestion of possible effect modification by dose of tolvaptan, in which benefit was observed in low-dose (≤15 mg/day) group (RR 0.48, 95% CI 0.23 to 1.02, p=0.05, I=54%), but not with high-dose (30 mg) group (RR 1.33, 95% CI 0.99 to 1.78, p=0.05, I=0%). However, tolvaptan add-on therapy reduced body weight in 2 days (standardised mean difference -0.49, 95% CI -0.64 to -0.34, p<0.00001, I=0%), increased sodium level (mean difference 1.56, 95% CI 0.04 to 3.07, p=0.04, I=0%).

CONCLUSION

The result suggests that comparing with the standard diuretic therapy, tolvaptan add-on therapy did not reduce the incidence of WRF and short-term mortality, however, it can decrease body weight and increase the sodium level in patients who are with ADHF. Further researches are still required for confirmation.

摘要

目的

使用利尿剂治疗急性失代偿性心力衰竭(ADHF)以改善充血状况可能会导致肾功能恶化(WRF),但托伐普坦附加疗法在降低ADHF患者WRF方面的临床疗效并不一致。本分析旨在评估托伐普坦附加疗法对降低ADHF患者WRF的效果。

方法

对托伐普坦附加疗法降低ADHF患者WRF的随机试验进行荟萃分析。检索MEDLINE、Embase和Cochrane对照试验中央注册库数据库,查找从建库至2017年10月31日的相关文章。两名审阅者筛选关于WRF、短期全因死亡率、体重减轻、血钠水平升高的文献,以计算合并相对危险度、加权均数差及相关的95%可信区间。根据I统计量使用固定效应或随机效应模型。

结果

纳入7项随机对照试验共937例患者进行分析。与对照组相比,托伐普坦附加疗法未改善肾功能恶化发生率(RR=0.78,95%CI为0.48至1.26,p=0.31,I=66%)和短期全因死亡率(RR=0.85,95%CI为0.47至1.56,p=0.61,I=0%)。亚组分析显示,托伐普坦剂量可能存在效应修饰,低剂量(≤15mg/天)组观察到有益效果(RR=0.48,95%CI为0.23至1.02,p=0.05,I=54%),而高剂量(30mg)组未观察到(RR=1.33,95%CI为0.99至1.78,p=0.05,I=0%)。然而,托伐普坦附加疗法在2天内可减轻体重(标准化均数差-0.49,95%CI为-0.64至-0.34,p<0.00001,I=0%),提高血钠水平(均数差1.56,95%CI为0.04至3.07,p=0.04,I=0%)。

结论

结果表明,与标准利尿剂治疗相比,托伐普坦附加疗法并未降低WRF发生率和短期死亡率,然而,它可降低ADHF患者的体重并提高血钠水平。仍需进一步研究予以证实。

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