Abstract: Background　Diuretics are a cornerstone treatment for heart failure，but some patients will gradually develop reduced sensitivity to diuretics，resulting in weakened or even disappeared diuretic effect after a long-term use of them，which is clinically called diuretic resistance. Diuretic resistance is independently associated with heart failure-related mortality，which cannot be cured by western medicine，but has been proven to be partially improved by Wenyang Lishui Recipes（WLR），a type of Chinese medicine treatment. Objective　To systematically evaluate the efficacy and safety of WLR in treating heart failure with diuretic resistance. Methods　The authors searched the databases of PubMed，Web of Science，The Cochrane Library，EMBase，CNKI，Wanfang，VIP and CBM to screen randomized controlled trials（RCTs） comparing WLR with western medicine treatment against western medicine treatment in heart failure with diuretic resistance patients from inception to January 2020. The major primary outcome indicators included 24-hour urine collection，and left ventricular ejection fraction （LVEF）. Secondary outcome indicators included N-terminal proB-type natriuretic peptide （NT-proBNP），clinical symptom response rate，and cardiac function improvement rate. Safety indicators included serum potassium and creatinine. The “Risk of bias' tool described in Cochrane Handbook （version 5.1.0） and the modified Jadad Scale were used to evaluate the quality of the included RCTs. RevMan 5.3 and Stata 12.0 were used for meta-analysis. Results　Fourteen RCTs were included，involving 932 patients. Meta-analysis revealed that compared with western medicine treatment alone，WLR with western medicine treatment could further increase the 24-hour urine collection〔MD=499.41，95%CI（287.26，711.55），P<0.000 01〕，improve the LVEF〔MD=5.25，95%CI（3.28，7.22），P<0.000 01〕，clinical symptom response rate〔RR=1.26，95%CI（1.16，1.37），P<0.000 01〕，cardiac function improvement rate〔RR=1.25，95%CI（1.14，1.38），P<0.000 01〕，and serum potassium level〔MD=0.19，95%CI（0.14，0.24），P<0.000 01〕，as well as further decrease the NT-proBNP〔MD=-594.14，95%CI（-796.95，-391.33），P<0.000 01〕. Subgroup analysis found that WLR with western medicine treatment showed greater effects on improving LVEF no matter the sample size was greater or less than 80〔MD=2.04，95%CI（0.64，3.44），P=0.004；MD=6.61，95%CI（5.17，8.04），P<0.000 01〕. Conclusion　WLR with western medicine treatment may have better clinical efficacy in patients with heart failure with diuretic resistance with good safety.However，more high-quality clinical studies are still needed to verify this conclusion.

Key words: Heart failure, Wenyang lishui herbal medicine, Diuretic resistance, Treatment outcome, Patient safety, Meta-analysis

摘要： 背景　利尿剂是心力衰竭治疗的基石药物，但部分长期应用利尿剂的患者对利尿剂的敏感性逐渐减低，导致利尿作用减弱甚至消失，临床中将这种现象称为利尿剂抵抗。利尿剂抵抗与心力衰竭患者的死亡率存在独立相关性，目前西医对此尚无特效药物，而中医采用温阳利水法治疗此类患者取得了一定的疗效。目的　系统评价温阳利水中药治疗心力衰竭合并利尿剂抵抗患者的疗效及安全性。方法　检索PubMed、Web of Science、The Cochrane Library、EMBase、中国知网（CNKI）、万方数据知识服务平台、中文科技期刊全文数据库（VIP）、中国生物医学文献数据库（CBM），检索时限为建库至2020年1月。筛选出应用温阳利水中药治疗心力衰竭合并利尿剂抵抗患者的随机对照试验，主要结局指标：24 h尿量，左心室射血分数（LVEF）。次要结局指标：N末端脑利钠肽前体（NT-proBNP），临床症状有效率，心功能改善率。安全性指标：血钾，肌酐。采用Cochrane Handbook评价标准和改良Jadad量表对纳入文献进行质量评价，运用RevMan 5.3和Stata 12.0软件进行Meta分析。结果　共纳入符合标准的文献14篇，932例患者，Meta分析结果显示，观察组24 h尿量〔MD=499.41，95%CI（287.26，711.55），P<0.000 01〕、LVEF〔MD=5.25，95%CI（3.28，7.22），P<0.000 01〕、临床症状有效率〔RR=1.26，95%CI（1.16，1.37），P<0.000 01〕、心功能改善率〔RR=1.25，95%CI（1.14，1.38），P<0.000 01〕、血钾〔MD=0.19，95%CI（0.14，0.24），P<0.000 01〕高于对照组，NT-proBNP低于对照组〔MD=-594.14，95%CI（-796.95，-391.33），P<0.000 01〕。对LVEF指标进行亚组分析结果显示，无论样本量大于80或小于80，观察组LVEF均高于对照组〔MD=2.04，95%CI（0.64，3.44），P=0.004〕、〔MD=6.61，95%CI（5.17，8.04），P<0.000 01〕。结论　在常规西药基础上联用温阳利水中药可以进一步改善心力衰竭合并利尿剂抵抗患者的临床疗效且安全性良好，但仍需更多高质量的临床研究加以验证。

关键词: 心力衰竭, 温阳利水, 利尿剂抵抗, 治疗结果, 病人安全, Meta分析