左旋氨氯地平与氨氯地平及不同剂量左旋氨氯地平治疗高血压有效性和安全性的meta分析

Efficacy and safety of S-amlodipine versus amlodipine and 2.5mg S-amlodipine versus 5.0mg S-amlodipine for hypertension: a systematic review and meta-analysis

目的系统评价左旋氨氯地平与氨氯地平比较,以及2.5 mg左旋氨氯地平与5.0 mg左旋氨氯地平比较治疗原发性高血压的有效性和安全性。方法计算机检索Medline、Embase、CENTRAL、ClinicalTrial.gov、中国知网、万方和维普数据库,检索时限均为建库至2018年1月,收集相关随机对照试验(randomized controlled trial,RCT)。由2名研究者独立筛选文献、提取资料并评价偏倚风险,采用RevMan 5.3软件进行meta分析。结果共纳入16个RCT,包括3 946例患者。meta分析结果显示:与氨氯地平相比,左旋氨氯地平降低颈动脉内膜中层厚度[均数差(mean difference,MD)=–0.21 mm,95%置信区间(confidence interval,CI)(–0.35,–0.07)mm,P=0.003]、脉压[MD=–5.90 mm Hg(1 mm Hg=0.133 kPa),95%CI(–8.57,–3.23)mm Hg,P<0.000 1]、收缩压[MD=–5.08 mm Hg,95%CI(–9.61,–0.55)mm Hg,P=0.03]、舒张压[MD=–4.60 mm Hg,95%CI(–7.82,–1.39)mm Hg,P=0.005]效果更好,不良反应发生率[风险比=0.55,95%CI(0.40,0.77),P=0.000 4]更低;但两组在改变左心室后壁厚度、心率、血压变异性方面差异均无统计学意义(P>0.05)。5.0 mg左旋氨氯地平降低收缩压[MD=4.17 mm Hg,95%CI(2.23,6.11)mm Hg,P<0.000 1]、舒张压[MD=1.84 mm Hg,95%CI(1.17,2.52)mm Hg,P<0.000 01]效果均优于2.5 mg左旋氨氯地平,但两组不良反应发生率差异无统计学意义(P>0.05)。所有纳入研究均未报告主要(终点)有效性结局指标,因而未能针对这些结局指标进行meta分析。结论与氨氯地平比较,左旋氨氯地平降血压、脉压效果略优于氨氯地平,在降低间接反映远期预后的颈动脉内膜中层厚度指标效果上更好,且不良事件发生率更低;与2.5 mg左旋氨氯地平比较,5.0 mg左旋氨氯地平降压效果更好,安全性相似,但高剂量组有更多不良反应发生的趋势。对于左旋氨氯地平治疗高血压在全因死亡率、心脑血管疾病死亡率和发病率等指标上的效果,因缺乏相关数据无法得出结论。受纳入研究数量和质量限制,该结论尚需进一步开展更多高质量、大样本的RCT进行验证。

Objective To assess the efficacy and safety of S-amlodipine versus amlodipine,and 2.5 mg S-amlodipine versus 5.0 mg S-amlodipine in treating hypertension.Methods Medline,Embase,CENTRAL,ClinicalTrials.gov,China National Knowledge Infrastructure,WanFang Data,and VIP databases were searched for randomized controlled trials(RCTs)about S-amlodipine for hypertension till January 2018.Two reviewers independently reviewed the literature,extracted data,and assessed the risk of bias of included RCTs.RevMan 5.3 software was used for meta-analysis.Results All together 16 RCTs involving 3 946 patients were included.The results of meta-analysis showed that:(1)S-amlodipine vs.amlodipine:the levels of reduction in intima-media thickness[mean difference(MD)=–0.21 mm,95%confidence interval(CI)(–0.35,–0.07)mm,P=0.003],pulse pressure[MD=–5.90 mm Hg(1 mm Hg=0.133 kPa),95%CI(–8.57,–3.23)mm Hg,P<0.000 1],systolic pressure[MD=–5.08 mm Hg,95%CI(–9.61,–0.55)mm Hg,P=0.03],and diastolic pressure[MD=–4.60 mm Hg,95%CI(–7.82,–1.39)mm Hg,P=0.005]were all higher in the S-amlodipine group than in the amlodipine group,and the incidence of adverse event[relative risk=0.55,95%CI(0.40,0.77),P=0.000 4]was lower in the S-amlodipine group.But no significant differences were found in changes of left ventricular posterior wall thickness,heart rate,blood pressure variability between the two groups.(2)2.5 mg S-amlodipine vs.5.0 mg S-amlodipine:the levels of reduction in systolic pressure[MD=4.17 mm Hg,95%CI(2.23,6.11)mm Hg,P<0.000 1]and diastolic pressure[MD=1.84 mm Hg,95%CI(1.17,2.52)mm Hg,P<0.000 01]were higher in the 5.0 mg S-amlodipine group than in the 2.5 mg S-amlodipine group,but no significant difference was found in the incidence of adverse event between the two groups.None of the primary outcomes was analyzed because they were not reported by any one of the included studies.Conclusions Current evidence shows that S-amlodipine is slightly superior to amlodipine in reducing intimamedia thickness which could indirectly reflect the effect of interventions on endpoint outcome measures,blood pressure,pulse pressure,and the incidence of adverse event.5.0 mg S-amlodipine is slightly superior to 2.5 mg S-amlodipine in reducing blood pressure,though comparable with the latter in the effect on incidence of adverse event.The effect of S-amlodipine on all the primary outcomes is unclear because none of the included studies reported on those.Due to limited quantity and quality of the included studies,more high quality studies are needed to verify the above conclusions.