低剂量与标准剂量替格瑞洛在中国急性冠脉综合征患者中有效性和安全性的系统评价

Systematic Review of Efficacy and Safety of Low-dose Versus Standard-dose Ticagrelor in Chinese Patients with Acute Coronary Syndrome

关键词:  急性冠脉综合征  低剂量  替格瑞洛  随机对照试验  meta分析

Key words:  acute coronary syndrome  low dose  ticagrelor  randomized controlled trial  meta-analysis

摘要:

目的 系统评价低剂量与标准剂量替格瑞洛在中国急性冠脉综合征(acute coronary syndrome,ACS)患者中的有效性和安全性。方法 检索MEDLINE、EMBASE、Cochrane Library、中国知网、维普期刊资源整合服务平台和万方数据知识服务平台,检索时限为各数据库建库起至2022年3月,获得中国ACS患者低剂量与标准剂量替格瑞洛抗血小板治疗的随机对照试验(randomized controlled trials,RCT),提取资料并按照Cochrane系统评价员手册5.2.0进行质量评价,采用Rev Man 5.3统计软件对其有效性终点事件和安全性终点事件的发生率进行meta分析。结果 共纳入17项RCTs合计2 225例患者。Meta分析结果显示,与标准剂量替格瑞洛相比,低剂量替格瑞洛未增加心血管死亡[RR=1.01,95%CI (0.55,1.87),P=0.96]、心肌梗死[RR=1.24,95%CI(0.66,2.30),P=0.50]和卒中[RR=1.43,95%CI(0.48,4.28),P=0.53]的发生风险,但可显著减少出血[RR=0.42,95%CI(0.35,0.51),P<0.000 01]、大出血[RR=0.45,95%CI(0.26,0.78),P=0.004]、轻微出血[RR=0.43,95%CI(0.35,0.54),P<0.000 01]和呼吸困难[RR=0.52,95%CI(0.37,0.73),P=0.000 2]的发生风险。结论 低剂量替格瑞洛可显著减少中国ACS患者出血性事件的发生风险,同时未增加缺血性事件的发生风险,可作为其抗血小板治疗的可选策略,但仍需结合患者的个体情况进行综合评估,且有待更大样本量的RCT加以验证。

Abstract:

OBJECTIVE To systematically evaluate the efficacy and safety of low-dose versus standard-dose ticagrelor in Chinese patients with acute coronary syndrome(ACS). METHODS Systematically searched databases of MEDLINE, EMBASE, Cochrane's Library, CNKI, CQVIP and Wanfang for randomized controlled trials(RCTs) comparing low-dose versus standard-dose ticagrelor in Chinese patients with ACS from the establishment of each database to March 2022. Meta-analysis was conducted for the incidence of efficacy endpoints and safety endpoints by using Rev Man 5.3 statistical software after data extraction and quality evaluation with Cochrane system evaluator manual 5.2.0. RESULTS Seventeen RCTs involving 2 225 patients were included for our meta-analysis. Compared with standard-dose of ticagrelor, low-dose of ticagrelor did not increase the risk of cardiovascular death[RR=1.01, 95%CI(0.55, 1.87), P=0.96], myocardial infarction[RR=1.24, 95%CI(0.66, 2.30), P=0.50] and stroke[RR=1.43, 95%CI(0.48, 4.28), P=0.53], but significantly reduced the risk of bleeding[RR=0.42, 95%CI(0.35, 0.51), P<0.000 01], major bleeding[RR=0.45, 95%CI(0.26, 0.78), P=0.004], minor or minimal bleeding[RR=0.43, 95%CI (0.35, 0.54), P<0.000 01] and dyspnea[RR=0.52, 95% CI(0.37, 0.73), P=0.000 2]. CONCLUSION Low-dose ticagrelor can significantly reduce the risk of bleeding events without increasing the risk of ischemic events in Chinese patients with ACS, which could be used as an alternative strategy for antiplatelet therapy. However, comprehensive evaluation is still needed in combination with the individual situation of patients and needs to be verified by RCT with a larger sample size.