Efficacy and safety of colchicine for the prevention of major cardiovascular and cerebrovascular events in patients with coronary artery disease: a systematic review and meta-analysis on 12 869 patients
Efficacy and safety of colchicine for the prevention of major cardiovascular and cerebrovascular events in patients with coronary artery disease: a systematic review and meta-analysis on 12 869 patients
复制标题
DOI：
10.1093/eurjpc/zwab045
复制
发表时间：
2021-03-29
影响因子：
8.3
通讯作者：
De Ferrari, Gaetano Maria
中科院分区：
文献类型：
--
作者：
Andreis, Alessandro;Imazio, Massimo;De Ferrari, Gaetano Maria
目的研究炎症在冠状动脉疾病（CAD）发病机制中的关键作用，迫切需要创新治疗方法。一些试验已经提出秋水仙碱作为CAD患者二级预防的治疗选择，但由于担心药物相关不良事件（DAEs）和证据矛盾，秋水仙碱的使用受到阻碍。本荟萃分析的目的是巩固秋水仙碱对冠心病患者二级预防的有效性和安全性的证据。方法和结果系统检索Medline、Scopus、Embase和Cochrane图书馆的电子书目数据库，以确定评估秋水仙碱与安慰剂对CAD患者心血管影响的随机对照试验（rct）。关注的结局是主要不良心脑血管事件（MACCE）和DAEs的发生。使用反方差随机效应模型汇总估计。共有11项rct，包括12869例患者被确定为符合条件。共有6501名患者接受秋水仙碱治疗，而6368名患者接受安慰剂治疗。平均随访6个月后(四分位范围,1 - 16),患者接受秋水仙碱的风险降低MACCE(6%比8.8%,相对危险度(RR) = 0.67, 95%可信区间(CI) 0.56 - -0.80,我2 = 19%),心肌梗死(3.3%比4.3%,RR = 0.76, 95% CI 0.61 - -0.96,我2 = 17%),冠状血管再生(2.9%比4.2%,RR = 0.61, 95% CI 0.42 - -0.89,我2 = 40%),中风(0.4%比0.9%,RR = 0.48, 95% CI 0.30 - -0.77,我2 = 0%),住院心血管原因(0.9%比2.9%,Rr = 0.32, 95% ci 0.12-0.87, i-2 = 0%)。秋水仙碱与胃肠道DAEs（11%比9.2%,RR = 1.67, 95% CI 1.20-2.34, I-2 = 76%）、肌痛（18%比16%，RR = 1.16, 95% CI 1.02-1.32, I-2 = 0%）和DAEs相关停药（4.1%比3%，RR = 1.54, 95% CI 1.02-2.32, I-2 = 65%）的风险增加相关。然而，较低的日剂量可以预防胃肠道DAEs和停药。秋水仙碱不会增加心血管死亡（0.7% vs. 1%, RR = 0.73, 95% CI 0.45-1.21, I-2 = 14%）、全因死亡（2% vs. 1.9%, RR = 1.01, 95% CI 0.71-1.43, I-2 = 16%）或其他DAEs的风险。结论秋水仙碱用于冠心病患者预防MACCE安全有效。
Aims The key role of inflammation in the pathogenesis of coronary artery disease (CAD) is an urgent call for innovative treatments. Several trials have proposed colchicine as a therapeutic option for secondary prevention in CAD patients but its utilization is hampered by fears about drug-related adverse events (DAEs) and conflicting evidences. The aim of this meta-analysis was to consolidate evidence on the efficacy and safety of colchicine for secondary prevention in patients with CAD. Methods and results A systematic search in electronic bibliographic databases of Medline, Scopus, Embase, and the Cochrane Library was performed to identify randomized controlled trials (RCTs) assessing the cardiovascular effects of colchicine in CAD patients, compared with placebo. Outcomes of interest were the occurrence of major adverse cardiovascular and cerebrovascular events (MACCE) and DAEs. Estimates were pooled using inverse-variance random-effects model. A total of 11 RCTs, including 12 869 patients, were identified as eligible. A total of 6501 patients received colchicine, while 6368 received placebo. After a median follow-up of 6 months (interquartile range, 1-16), patients receiving colchicine had a lower risk of MACCE [6% vs. 8.8%, relative risk (RR) = 0.67, 95% confidence interval (CI) 0.56-0.80, I-2 = 19%], myocardial infarction (3.3% vs. 4.3%, RR = 0.76, 95% CI 0.61-0.96, I-2 = 17%), coronary revascularization (2.9% vs. 4.2%, RR = 0.61, 95% CI 0.42-0.89, I-2 = 40%), stroke (0.4% vs. 0.9%, RR = 0.48, 95% CI 0.30-0.77, I-2 = 0%), hospitalization for cardiovascular cause (0.9% vs. 2.9%, RR = 0.32, 95% CI 0.12-0.87, I-2 = 0%). Colchicine was associated with an increased risk of gastrointestinal DAEs (11% vs. 9.2%, RR = 1.67, 95% CI 1.20-2.34, I-2 = 76%), myalgia (18% vs. 16%, RR = 1.16, 95% CI 1.02-1.32, I-2 = 0%) and DAEs-related discontinuation (4.1% vs. 3%, RR = 1.54, 95% CI 1.02-2.32, I-2 = 65%). However, gastrointestinal DAEs and discontinuation may be prevented with a lower daily dose. Colchicine did not increase the risk of cardiovascular death (0.7% vs. 1%, RR = 0.73, 95% CI 0.45-1.21, I-2 = 14%), all-cause death (2% vs. 1.9%, RR = 1.01, 95% CI 0.71-1.43, I-2 = 16%), or other DAEs. Conclusions The use of colchicine in patients with CAD is safe and efficacious for MACCE prevention.