标准治疗方案联合糖皮质激素对川崎病冠状动脉瘤发生率影响的Meta分析

目的评价标准治疗方案+糖皮质激素对川崎病(KD)冠状动脉瘤(CAA)发生率的影响。方法制定原始文献的纳入标准及检索策略,检索Medline、EMBASE、Cochrane图书馆、万方数据库、中国期刊全文数据库和中国维普数据库,检索时间均从建库至2010年6月。纳入标准治疗方案(大剂量IVIG+阿司匹林)+糖皮质激素对KD CAA发生率影响的相关文献。依据KD诊断标准、研究设计、冠状动脉影像学随访时间和冠状动脉检查是否采用盲法进行文献质量评价。计数资料采用相对危险度(RR)及其95%CI表示;计量资料采用加权均数差(WMD)及其95%CI表示。采用Stata11.0软件进行Meta分析。结果 7篇文献进入Meta分析,均为英文文献,其中4篇为RCT文献,3篇为回顾性对照研究。文献质量评价结果显示,评分2分3篇,5分1篇,6分3篇。Meta分析结果显示,标准治疗方案+糖皮质激素可显著降低CAA的发生率(RR=0.34,95%CI:0.13~0.89)。由于纳入文献间存在显著的异质性,进行亚组分析,显示研究设计(RCT和非RCT)、样本量(100和100)、糖皮质激素的类型(泼尼松龙和其他)是异质性产生的原因。RCT研究及样本量100文献的Meta分析结果显示,标准治疗方案+糖皮质激素未能显著降低CAA的发生率(RR分别为0.79和0.73,95%CI分别为0.43~1.43和0.42~1.28)。标准治疗方案+糖皮质激素可显著降低IVIG再治疗率(RR=0.48,95%CI:0.32~0.72),显著减少发热天数(WMD=-1.66d,95%CI:-2.58~-0.73d),对不良反应事件发生率无显著影响(RR=0.87,95%CI:0.35~2.16)。结论现有证据提示标准治疗方案+糖皮质激素未能显著降低CAA的发生率,可减少IVIG再治疗率和发热天数。

Conventional primary therapy combined with corticosteroid on coronary artery aneurysm formation in Kawasaki disease: a meta-analysis

Objective To assess the effect of conventional primary therapy combined with corticosteroid on coronary artery aneurysm formation in Kawasaki disease. Methods Studies were identified by a systematic search in MEDLINE, EMBASE, Cochrane Library， WANFANG, CNKI and VIP Database from its establishment to June 2010. All clinical controlled trials comparing the addition of corticosteroids to conventional primary therapy for Kawasaki disease were eligible. Quality assessment was investigated according to the Kawasaki disease diagnosis, study design and blinding of outcome detection. The weighted mean difference (WMD) for duration of fever after initiation of therapy and pooled relative risk (RR) for coronary artery aneurysm, re-treatments with intravenous immunoglobulin (IVIG) and adverse events were compiled. Heterogeneity was evaluated by stratified analysis. Stata 11.0 software was used to perform the meta analysis. Results Two hundred and twenty two studies were identified from database search. Thirty studies were selected for further assessment through reading the title and abstract. Seven eligible studies (4 randomized controlled trials and 3 comparative studies) were enrolled in the meta-analysis according to the further assessment. Quality assessments results showed three sudies were scored 2, 3 were scored 6, 1 was scored 5, respectively. Meta-analysis showed the additional corticosteroids therapy to standard therapy was associated with a significant 66% risk reduction of coronary artery aneurysm formation (RR=0.34, 95% CI:0.13-0.89). The overall test for heterogeneity among studies was significant (P=0.06, I2=53.6%). The incidence rate of coronary artery aneurysm was not significantly different in RCT(RR=0.79，95％CI:0.43-1.43), large size samples(>100)(RR=0.73,95%CI:0.42-1.28). Corticosteroid therapy decreased the fever duration after initiation of therapy (WMD=-1.66 d, 95%CI:-2.58 to -0.73 d) and risk of re-treatments with IVIG (RR=0.43, 95%CI:0.31-0.61）but did not decrease the risk of adverse events (RR=0.87, 95%CI: 0.35-2.16). Conclusions The addition of corticosteroids to standard therapy did not decrease the incidence of coronary aneurysms, but could decrease the rates of re-treatment with IVIG and the fever duration after initiation of therapy.