Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada.
Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, British Columbia, Canada.
Pharmacotherapy. 2020 Jun;40(6):575-583. doi: 10.1002/phar.2401. Epub 2020 May 5.
Despite advancements in medical and interventional therapy, patients with cardiovascular disease (CVD) continue to have residual risk for recurrent cardiovascular events. Colchicine has a unique antiinflammatory mechanism that has generated interest in its potential use as a secondary cardiovascular preventive therapy. The objective of this systematic review was to evaluate the evidence for long-term (6 months or more) colchicine therapy in patients with established CVD. A search of Medline and Embase from inception to February 2020 was performed. Included were randomized controlled trials (RCTs) or propensity score-matched observational studies that compared colchicine (at any dose) with placebo or no treatment. Outcomes of interest included any major adverse cardiovascular event, cardiovascular hospitalization, coronary artery restenosis, cardiovascular death, or all-cause death. Five RCTs were included. The dose of colchicine ranged from 0.5 mg/day to 0.6 mg twice/day, and follow-up ranged from ~6-36 months. Two trials (one double blind and one single blind) showed a reduction in composite outcomes of major adverse cardiovascular events. One study failed to demonstrate a benefit with colchicine in restenosis or recurrent ischemia after angioplasty; however, it was conducted before the routine use of modern percutaneous coronary intervention and medical therapies. In contrast, a more recent trial found that colchicine reduced the rate of in-stent restenosis in patients who received a bare metal stent. Finally, one trial in patients with heart failure with reduced ejection fraction did not observe a benefit in death or heart failure hospitalization with colchicine despite a reduction in inflammatory markers. No trial demonstrated a reduction in cardiovascular or all-cause death, and most trials showed an increase in the rate of diarrhea with colchicine. Overall, colchicine has demonstrated promising results for the secondary prevention of CVD; however, further studies are required to confirm these findings before colchicine can be routinely recommended in practice.
尽管在医学和介入治疗方面取得了进展,但心血管疾病 (CVD) 患者仍存在心血管事件复发的残余风险。秋水仙碱具有独特的抗炎机制,这使其作为二级心血管预防治疗的潜在用途受到关注。本系统评价的目的是评估长期(6 个月或以上)秋水仙碱治疗在已确诊 CVD 患者中的疗效。从建库到 2020 年 2 月,对 Medline 和 Embase 进行了检索。纳入的研究包括比较秋水仙碱(任何剂量)与安慰剂或不治疗的随机对照试验 (RCT) 或倾向评分匹配的观察性研究。感兴趣的结局包括任何主要不良心血管事件、心血管住院、冠状动脉再狭窄、心血管死亡或全因死亡。纳入了 5 项 RCT。秋水仙碱的剂量范围为 0.5mg/天至 0.6mg 每天两次,随访时间为~6-36 个月。两项试验(一项双盲,一项单盲)显示主要不良心血管事件的复合结局减少。一项研究未能证明在经皮冠状动脉介入治疗和药物治疗常规应用之前进行的血管成形术后再狭窄或复发性缺血中使用秋水仙碱有益;然而,一项研究未能证明在经皮冠状动脉介入治疗和药物治疗常规应用之前进行的血管成形术后再狭窄或复发性缺血中使用秋水仙碱有益。相比之下,一项最近的试验发现,在接受裸金属支架的患者中,秋水仙碱可降低支架内再狭窄的发生率。最后,一项在射血分数降低的心力衰竭患者中进行的试验发现,尽管炎症标志物减少,但秋水仙碱并未降低死亡或心力衰竭住院的风险。没有试验表明心血管或全因死亡减少,大多数试验显示秋水仙碱增加腹泻的发生率。总的来说,秋水仙碱在 CVD 的二级预防方面显示出了有希望的结果;然而,在秋水仙碱可以常规推荐用于临床实践之前,还需要进一步的研究来证实这些发现。