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用于治疗静脉曲张出血的血管活性药物:随机临床试验的混合治疗比较网络荟萃分析和试验序贯分析

Vasoactive Agents for the Management of Variceal Bleeding: A Mixed Treatment Comparison Network Meta-analysis and Trial Sequential Analysis of Randomized Clinical Trials.

作者信息

Sridharan Kannan, Sivaramakrishnan Gowri

机构信息

Department of Pharmacology and Therapeutics, College of Medicine and Medical Sciences, Arabian Gulf University, Manama, Bahrain.

School of Oral Health, College of Medicine, Nursing and Health Sciences, Fiji National University, Suva, Fiji Islands.

出版信息

Drug Res (Stuttg). 2019 Sep;69(9):487-495. doi: 10.1055/a-0846-3071. Epub 2019 Feb 18.

Abstract

BACKGROUND

Vasoactives such as terlipressin, somatostatin, vasopressin, octreotide and nitrates are commonly used to treat variceal bleeding. The present study is a network meta-analysis comparing the efficacy and safety of the above vasoactive agents for treating variceal bleeding.

METHODS

Electronic databases were searched for appropriate randomized clinical trials evaluating vasoactives in cirrhotic patients with variceal bleeding. Random-effects model was used to generate the pooled estimates. Mortality was the primary outcome and bleeding control, re-bleeding rate, hospital stay, blood transfusion requirements and adverse events were the secondary outcome measures.

RESULTS

Fifty randomized clinical trials were included of which 37 were included for the primary outcome. The overall analysis did not reveal any significant difference in the mortality risk between any of the vaso-active drugs except for terlipressin that had statistically significant benefits from direct pooled estimates. Somatostatin and terlipressin showed significant reduction in the mortality risks at 24 h. Terlipressin significantly reduced re-bleeding rate; somatostatin and vasopressin were associated with better hemostasis; and terlipressin and vasopressin significantly reduced the requirement for blood transfusion. Terlipressin, vasopressin and glyceryltrinitrate/vasopressin were also associated with increased risk of adverse events.

CONCLUSION

Terlipressin could be the best agent in the vasoconstrictor category for managing variceal bleeding. Somatostatin and vasopressin can serve as alternatives.

摘要

背景

特利加压素、生长抑素、血管加压素、奥曲肽和硝酸盐等血管活性药物常用于治疗静脉曲张出血。本研究是一项网状荟萃分析,比较上述血管活性药物治疗静脉曲张出血的疗效和安全性。

方法

检索电子数据库,查找评估血管活性药物治疗肝硬化静脉曲张出血患者的合适随机临床试验。采用随机效应模型生成汇总估计值。死亡率是主要结局指标,出血控制、再出血率、住院时间、输血需求和不良事件是次要结局指标。

结果

纳入50项随机临床试验,其中37项纳入主要结局分析。总体分析未发现任何血管活性药物之间的死亡率风险有显著差异,但特利加压素经直接汇总估计有统计学显著益处。生长抑素和特利加压素在24小时时显示出死亡率风险显著降低。特利加压素显著降低再出血率;生长抑素和血管加压素与更好的止血效果相关;特利加压素和血管加压素显著降低输血需求。特利加压素、血管加压素和硝酸甘油/血管加压素也与不良事件风险增加相关。

结论

特利加压素可能是血管收缩剂类别中治疗静脉曲张出血的最佳药物。生长抑素和血管加压素可作为替代药物。

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