肾素血管紧张素系统阻断剂用于脑卒中二级预防的网状Meta分析

Efficacy of different renin-angiotensin system blockers in patients with prior stroke: a network meta-analysis

目的系统评价不同肾素血管紧张素系统阻断剂对脑卒中二级预防和降低卒中后主要血管事件发生率的有效性。方法计算机检索PubMed、The Cochrane Library、EMbase、CNKI、CBM和VIP数据库,搜集关于血管紧张素受体拮抗剂及血管紧张素转换酶抑制剂对脑卒中二级预防的随机对照试验(RCT),检索时限均为建库至2018年11月1日。由2名研究者独立筛选文献、提取资料并评价纳入研究的偏倚风险后,采用Stata 15.1软件进行网状Meta分析。结果共纳入6个RCT,包括25 620例患者。网状Meta分析结果显示:在降低脑卒中复发率方面,坎地沙坦[RR=0.40,95%CI(0.16,0.99)]和缬沙坦[RR=0.22,95%CI(0.07,0.76)]优于安慰剂;缬沙坦优于替米沙坦[RR=0.24,95%CI(0.07,0.81)]、雷米普利[RR=0.26,95%CI(0.07,0.93)]和培哚普利[RR=0.23,95%CI(0.07,0.81)]。在降低卒中后主要血管事件发生率方面,坎地沙坦[RR=0.39,95%CI(0.21,0.74)]、缬沙坦[RR=0.27,95%CI(0.11,0.64)]及雷米普利[RR=0.76,95%CI(0.60,0.95)]优于安慰剂;缬沙坦优于替米沙坦[RR=0.29,95%CI(0.12,0.68)]、雷米普利[RR=0.36,95%CI(0.15,0.88)]和培哚普利[RR=0.28,95%CI(0.12,0.68)];坎地沙坦优于替米沙坦[RR=0.42,95%CI(0.22,0.79)]及培哚普利[RR=0.41,95%CI(0.21,0.79)]。7种肾素血管紧张素系统阻断剂的排序结果为:缬沙坦>氨氯地平>坎地沙坦>雷米普利>替米沙坦>培哚普利>安慰剂。结论当前证据显示,缬沙坦与坎地沙坦能降低卒中复发率及卒中后主要血管事件发生率;雷米普利能降低卒中后主要血管事件发生率;缬沙坦可能是脑卒中二级预防的最佳肾素血管紧张素系统阻断剂。受纳入研究数量的限制,上述结论尚待更多高质量研究予以验证。

Objectives To systematically review the efficacy of different rennin-angiotensin system blockers in prevention of stroke recurrence and reduction of major vascular events in patients with prior stroke. Methods PubMed,The Cochrane Library, EMbase, CNKI, CBM and VIP databases were electronically searched to collect randomized controlled trials(RCTs) on the efficacy of ACEIs and ARBs for stroke secondary prevention from inception to November1 st, 2018. Two reviewers independently screened literature, extracted data and assessed risk of bias of included studies.Network meta-analysis was then performed by using Stata 15.1 software. Results A total of 6 RCTs involving 25 620 patients were included. The results of network meta-analysis showed that: in prevention of stroke recurrence, candesartan(RR=0.40, 95%CI 0.16 to 0.99) and valsartan(RR=0.22, 95%CI 0.07 to 0.76) were significantly lower than placebo;valsartan was lower than telmisartan(RR=0.24, 95%CI 0.07 to 0.81), ramipril(RR=0.26, 95%CI 0.07 to 0.93) and perindopril(RR=0.23, 95%CI 0.07 to 0.81). For reducing the major vascular events after stroke, candesartan(RR=0.39,95%CI 0.21 to 0.74), valsartan(RR=0.27, 95%CI 0.11 to 0.64) and ramipril(RR=0.76, 95%CI 0.60 to 0.95) were significantly lower than placebo;valsartan was lower than telmisartan(RR=0.29, 95%CI 0.12 to 0.69), ramipril(RR=0.36,95%CI 0.15 to 0.88) and perindopril(RR=0.28, 95%CI 0.12 to 0.68);candesartan was lower than telmisartan(RR=0.42,95%CI 0.22 to 0.79) and perindopril(RR=0.41, 95%CI 0.21 to 0.79). Conclusions Current evidence shows that valsartan and candesartan can reduce the stroke recurrence and major vascular events after stroke. Ramipril can reduce the major vascular event in patients with prior stroke. Valsartan might be the best option in both outcomes. Due to limited quantity of the included studies, more high quality studies are required to verify above conclusions.