丹参多酚酸盐注射液联合西医常规治疗对慢性心力衰竭疗效及安全性的系统评价及试验序贯分析

Systematic review and trial sequential analysis of efficacy and safety of Salvia Miltiorrhiza Polyphenols Injection combined with conventional western medicine in treatment of chronic heart failure

目的系统评价丹参多酚酸盐注射液联合西医常规治疗对慢性心力衰竭的有效性和安全性。方法计算机检索中国知网、万方、维普、PubMed等数据库中相关随机对照试验(randomized controlled trials,RCTs),检索时间限定为建库至2022年3月20日。采用偏倚风险评估工具进行文献质量评价,使用RevMan 5.3、Stata 15.0软件进行Meta分析,通过TSA 0.9.5.10 Beta软件进行试验序贯分析,并按照GRADE标准进行证据质量评价。结果最终共纳入23个RCTs,共计2421例患者,纳入研究的整体方法学质量较低。Meta分析结果显示,与西医常规治疗相比,联合丹参多酚酸盐注射液可显著提高临床总有效率[OR=3.95,95%CI(2.92,5.35),P<0.00001],降低Lee心衰评分[MD=−0.95,95%CI(−1.37,−0.52),P<0.0001],提高6 min步行距离[MD=44.50,95%CI(32.02,56.97),P<0.00001],降低血浆B型脑钠肽(B-type natriuretic peptide,BNP)浓度[MD=−74.78,95%CI(−89.24,−60.33),P<0.00001];改善心功能指标,包括提高射血分数(left ventricular ejection fraction,LVEF)[MD=5.33,95%CI(4.33,6.32),P<0.00001],降低左室收缩末期内径(left ventricular end systolic diameter,LVESD)[MD=−5.73,95%CI(−8.04,−3.43),P<0.00001]、左室舒张末期内径(left ventricular enddiastolic diameter,LVEDD)[MD=−5.12,95%CI(−7.16,−3.08),P<0.00001]及室间隔厚度(interventricular septal thickness,IVST)[MD=−1.12,95%CI(−1.60,−0.64),P<0.00001],提高心输出量(cardiac output,CO)[MD=1.12,95%CI(1.00,1.23),P<0.00001]、心脏指数(cardiac index,CI)[MD=1.12,95%CI(1.00,1.25),P<0.00001]及每搏量(stroke volume,SV)[MD=9.34,95%CI(5.39,13.29),P<0.00001];降低炎症指标,包括白细胞介素-6(interleukin-6,IL-6)[MD=−1.84,95%CI(−2.36,−1.31),P<0.00001]、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)[MD=−0.74,95%CI(−0.83,−0.66),P<0.00001]及超敏C反应蛋白(high-sensitivity C-reactive protein,hs-CRP)[MD=−0.97,95%CI(−1.27,−0.67),P<0.00001];降低心型脂肪酸结合蛋白(heart fatty acid binding protein,H-FABP)表达[MD=−9.74,95%CI(−12.21,−7.27),P<0.00001]。在不良反应发生率方面,两组比较差异无统计学意义[RR=0.63,95%CI(0.18,2.17),P=0.47]。试验序贯分析进一步肯定了联合丹参多酚酸盐注射液对慢性心力衰竭患者的疗效。GRADE证据质量分级显示临床总有效率为中等质量证据,Lee心衰评分、LVESD等8项结局指标均为低质量证据,其余均为极低质量证据。结论与西医常规治疗相比,联合丹参多酚酸盐注射液能显著提高临床疗效,无明显不良反应,然而证据等级不高,期待开展更多高质量、大样本、多中心的RCTs,为丹参多酚酸盐注射液治疗慢性心力衰竭提供更充分的循证证据。

Objective To systematically evaluate the efficacy and safety of conventional western medicine combined with Salvia Miltiorrhiza Polyphenols Injection in the treatment of chronic heart failure.Methods Relevant RCTs in CNKI,Wanfang,VIP,PubMed and other databases were searched by computer,and the search time was limited from the establishment of the database to March 20,2022.The risk of bias assessment tool was used to evaluate the quality of the literature,RevMan 5.3 and Stata15.0 software were used for Metaanalysis,and TSA 0.9.5.10 Beta software was used for trial sequential analysis(TSA),and the quality of evidence was evaluated according to GRADE standards.Results A total of 23 RCTs(2421 patients)were finally included,and the overall methodological quality of the included studies was low.Meta-analysis results showed that compared with conventional western medicine,combined with Salvia Miltiorrhiza Polyphenols Injection could significantly improve the clinical total effective rate[OR=3.95,95%CI(2.92,5.35),P<0.00001],reduce Lee heart failure score[MD=−0.95,95%CI(−1.37,−0.52),P<0.0001],increase 6 min walking distance[MD=44.50,95%CI(32.02,56.97),P<0.00001],decrease plasma B-type natriuretic peptide(BNP)concentration[MD=−74.78,95%CI(−89.24,−60.33),P<0.00001],improve cardiac function indicators,including increased left ventricular ejection fraction(LVEF)[MD=5.33,95%CI(4.33,6.32),P<0.00001],decreased left ventricular end systolic diameter(LVESD)[MD=−5.73,95%CI(−8.04,−3.43),P<0.00001],left ventricular end diastolic diameter(LVEDD)[MD=−5.12,95%CI(−7.16,−3.08),P<0.00001]and interventricular septal thickness(IVST)[MD=−1.12,95%CI(−1.60,−0.64),P<0.00001],increased cardiac output(CO)[MD=1.12,95%CI(1.00,1.23),P<0.00001],cardiac index(CI)[MD=1.12,95%CI(1.00,1.25),P<0.00001]and stroke volume(SV)[MD=9.34,95%CI(5.39,13.29),P<0.00001],reduced inflammatory markers,including interleukin-6(IL-6)[MD=−1.84,95%CI(−2.36,−1.31),P<0.00001],tumor necrosis factor-α(TNF-α)[MD=−0.74,95%CI(−0.83,−0.66),P<0.00001]and high-sensitivity C-reactive protein(hs-CRP)[MD=−0.97,95%CI(−1.27,−0.67),P<0.00001],decreased heart fatty acid binding protein(H-FABP)expression[MD=−9.74,95%CI(−12.21,−7.27),P<0.00001],there was no statistical difference in the incidence of adverse reactions between the two groups[RR=0.63,95%CI(0.18,2.17),P=0.47].TSA further affirmed the efficacy of the combined with Salvia Miltiorrhiza Polyphenols Injection in treatment of chronic heart failure.The GRADE evidence quality classification showed that the total effective rate was moderate quality evidence,the Lee heart failure score,LVESD and other eight outcome indicators were all low-quality evidence,and the rest were very low-quality evidence.Conclusion Compared with conventional western medicine treatment,combined with Salvia Miltiorrhiza Polyphenols Injection could significantly improve the clinical efficacy without obvious adverse reactions.However,the level of evidence is insufficient,and we look forward to conducting more high-quality,large-sample,multi-center RCTs to provide more sufficient evidence-based evidence for Salvia Miltiorrhiza Polyphenols Injection in the treatment of chronic heart failure.