Adverse events of colchicine for cardiovascular diseases: a comprehensive meta-analysis of 14 188 patients from 21 randomized controlled trials
Adverse events of colchicine for cardiovascular diseases: a comprehensive meta-analysis of 14 188 patients from 21 randomized controlled trials
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DOI：
10.2459/jcm.0000000000001157
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发表时间：
2021-08-01
影响因子：
3
通讯作者：
De Ferrari, Gaetano M.
中科院分区：
文献类型：
--
作者：
Andreis, Alessandro;Imazio, Massimo;De Ferrari, Gaetano M.
秋水仙碱在心血管领域有着新兴的作用，尽管对副作用的担忧，特别是胃肠道，限制了其处方。我们的目的是评估报告的副作用秋水仙碱心血管适应症。方法对已发表的秋水仙碱治疗心血管疾病的随机对照试验进行荟萃分析。采用随机效应荟萃分析评估不良事件和停药的风险。使用Egger检验评估发表偏倚，并进行荟萃回归以评估异质性来源。结果14188例患者中，7136例接受秋水仙碱治疗，7052例接受安慰剂治疗。15.3%与13.9%的患者报告了秋水仙碱的任何不良事件[相对风险（RR）1.26，95%置信区间（CI）0.96-1.64，P = 0.09]。胃肠道事件的报告率分别为16.1%和12.2%（RR 2.16，95% CI 1.50-3.12，P < 0.001），腹泻的报告率分别为12.5%和8.1%（RR 2.77，95% CI 1.55-4.94，P < 0.001）。胃肠道事件的风险随着每日剂量和治疗持续时间的缩短而增加。在21例与18%的患者中观察到肌痛（RR 1.16，95% CI 1.02-1.32，P = 0.03）。秋水仙素治疗不会增加其他不良事件，如肌毒性、肝脏不良事件、血液学不良事件、皮肤不良事件、感染或死亡。秋水仙碱停药率分别为4.8%和3.4%（RR 1.54，95%CI 1.20-1.99，P < 0.001）。结论秋水仙碱与胃肠道事件和肌痛的风险增加有关，但与其他不良事件无关。较低剂量（0.5 mg/天）可以避免胃肠道事件的风险，并且与治疗持续时间呈负相关，可能是由于早期停药或药物耐受性。
Aims Colchicine has an emerging role in the cardiovascular field, although, concerns for side effects, especially gastrointestinal, limit its prescription. We aimed at evaluating reported side effects of colchicine for cardiovascular indications. Methods We performed a meta-analysis of published randomized controlled trials on colchicine for the treatment of cardiovascular diseases. Random-effects meta-analysis was used to assess the risk of adverse events and drug withdrawal. Publication bias was assessed using the Egger test, and meta-regression was performed to assess sources of heterogeneity. Results Among 14 188 patients, 7136 patients received colchicine while the other 7052 received placebo. The occurrence of any adverse event with colchicine was reported in 15.3 vs. 13.9% patients [relative risk (RR) 1.26, 95% confidence interval (CI) 0.96-1.64, P = 0.09]. Gastrointestinal events were reported in 16.1 vs. 12.2% (RR 2.16, 95% CI 1.50-3.12, P < 0.001), while diarrhea was reported in 12.5 vs. 8.1% (RR 2.77, 95% CI 1.55-4.94, P < 0.001). The risk of gastrointestinal events increased with daily dose and shorter treatment duration. Myalgias were observed in 21 vs. 18% patients (RR 1.16, 95% CI 1.02-1.32, P = 0.03). Other adverse events such as myotoxicity, hepatic adverse events, hematologic adverse events, cutaneous adverse events, infection or death were not increased by colchicine treatment. Colchicine discontinuation was reported in 4.8 vs. 3.4% patients (RR 1.54, 95% CI 1.20-1.99, P < 0.001). Conclusion Colchicine is associated with increased risk of gastrointestinal events and myalgias, but not of other adverse events. The risk of gastrointestinal events may be avoided with lower dose (0.5 mg/daily) and is inversely related to treatment duration, possibly due to early drug discontinuation or drug tolerance.