托伐普坦治疗肝硬化腹水伴低钠血症疗效与安全性的Meta分析

Efficacy and Safety of Tolvaptan in the Treatment of Liver Cirrhosis Ascites with Hyponatremia:a Meta-analysis

目的:系统评价托伐普坦治疗肝硬化腹水伴低钠血症的疗效和安全性,为临床用药提供参考。方法:计算机检索Cochrane图书馆、PubMed、中国知网(CNKI)以及万方数据库等,收集托伐普坦联合常规治疗方案(试验组)对比单纯常规方案加或不加安慰剂(对照组)治疗肝硬化腹水伴低钠血症的随机对照试验(RCT),提取相关资料并按照改良的Jadad评分量表评价纳入研究质量,采用RevMan 5.3统计软件对数据进行Meta分析。结果:共纳入16项RCT,合计1 271例患者。Meta分析结果显示,试验组患者血钠浓度[MD=6.51,95%CI(4.64,8.39),P<0.001]、24 h尿量[MD=1.36,95%CI(1.01,1.70),P<0.001]、腹水及水肿治疗总有效率[RD=0.27,95%CI(0.20,0.35),P<0.001]、体质量改善[MD=-1.11,95%CI(-1.31,-0.91),P<0.001]和腹围改善[MD=-2.13,95%CI(-2.96,-1.31),P<0.001]均显著优于对照组,差异均有统计学意义。两组患者治疗前后及组间比较,血钾、血压、心率、总胆红素、血肌酐和尿素氮水平,差异均无统计学意义(P>0.05);试验组患者丙氨酸转氨酶水平显著低于对照组,差异有统计学意义(P=0.003)。亚组分析显示,仅对照组使用传统利尿药或两组均未使用传统利尿药时,两组24 h尿量比较差异无统计学意义(P>0.05),其余亚组试验组患者血钠浓度和24 h尿量均显著高于对照组,差异有统计学意义(P<0.001)。试验组患者口渴、口干、尿频和失眠等不良反应发生率显著高于对照组,差异均有统计学意义(P<0.05);总不良反应发生率较对照组稍高,但差异无统计学意义(P>0.05)。结论:托伐普坦治疗肝硬化腹水伴低钠血症疗效较好,可以显著改善患者血钠浓度、24 h尿量、腹水及水肿、体质量及腹围,且几乎不影响血钾、心率、血压和肝肾功能,但应注意口渴等不良反应的发生。

OBJECTIVE： To evaluate the efficacy and safety of tolvaptan in the treatment of liver cirrhosis ascites with hyponatremia systematically,in order to provide reference for clinical drug use. METHODS：Retrieved from The Cochrane Library,PubMed,CNKI and Wanfang database,etc.,randomized controlled trials（RCTs） about tolvaptan combined with routine treatment plan（trial group）versus routine treatment plan with or without placebo（control group）in the treatment of liver cirrhosis ascites with hyponatremia were collected. The qualities of included studies were evaluated according to modified Jadad scale after extracting data. Meta-analysis was performed by using RevMan 5.3 statistical software. RESULTS：A total of 16 RCTs were included,involving 1 271 patients. The results of Meta-analysis showed that serum sodium concentration [MD=6.51,95%CI（4.64,8.39）,P〈0.001],24 h urine volume [MD=1.36,95%CI（1.01,1.70）,P〈0.001],response rate of ascites and edema [RD=0.27,95%CI（0.20,0.35）,P〈0.001],body weight improvement [MD=-1.11,95%CI（-1.31,-0.91）,P〈0.001] and abdomen circumference improvement [MD=-2.13,95%CI（-2.96,-1.31）,P〈0.001] of trial group were significantly superior to those of control group,with statistical significance. There was no statistical significance in the levels of blood potassium,blood pressure,heart rate,TBi L,Scr or BUN between 2 groups before and after treatment（P〉0.05）. The level of ALT in trial group was significantly lower than control group,with statistical significance（P=0.003）. Subgroup analysis showed that there was no statistical significance in 24 h urine volume when traditional diuretics were given only in control group or not used in two groups（P〉0.05）;the serum sodium concentration and24 h urine volume of other subgroups were significantly higher than those of control group,with statistical significance（P〈0.001）.The incidence of ADR in trial group was higher than control group as dry mouth,thirst,frequent urination,insomnia,with statistical significance（P〈0.05）. Total incidence of ADR in trial group was slightly higher than control group,without statistical significance（P〉0.05）. CONCLUSIONS：Tolvaptan has good therapeutic efficacy for liver cirrhosis ascites with hyponatremia,can effectively improves serum sodium concentration,24 h urine volume,ascites and edema,body weight and abdomen circumference,but rarely affects blood potassium,heart rate,blood pressure,liver and renal function. However,ADR as thirst should be paid attention.