Heart Care Western Australia, Perth, Western Australia, Australia.
McMaster University, Hamilton, Ontario, Canada.
J Am Coll Cardiol. 2013 Jan 29;61(4):404-410. doi: 10.1016/j.jacc.2012.10.027. Epub 2012 Dec 19.
The objective of this study was to determine whether colchicine 0.5 mg/day can reduce the risk of cardiovascular events in patients with clinically stable coronary disease.
The presence of activated neutrophils in culprit atherosclerotic plaques of patients with unstable coronary disease raises the possibility that inhibition of neutrophil function with colchicine may reduce the risk of plaque instability and thereby improve clinical outcomes in patients with stable coronary disease.
In a clinical trial with a prospective, randomized, observer-blinded endpoint design, 532 patients with stable coronary disease receiving aspirin and/or clopidogrel (93%) and statins (95%) were randomly assigned colchicine 0.5 mg/day or no colchicine and followed for a median of 3 years. The primary outcome was the composite incidence of acute coronary syndrome, out-of-hospital cardiac arrest, or noncardioembolic ischemic stroke. The primary analysis was by intention-to-treat.
The primary outcome occurred in 15 of 282 patients (5.3%) who received colchicine and 40 of 250 patients (16.0%) assigned no colchicine (hazard ratio: 0.33; 95% confidence interval [CI] 0.18 to 0.59; p < 0.001; number needed to treat: 11). In a pre-specified secondary on-treatment analysis that excluded 32 patients (11%) assigned to colchicine who withdrew within 30 days due to intestinal intolerance and a further 7 patients (2%) who did not start treatment, the primary outcome occurred in 4.5% versus 16.0% (hazard ratio: 0.29; 95% CI: 0.15 to 0.56; p < 0.001).
Colchicine 0.5 mg/day administered in addition to statins and other standard secondary prevention therapies appeared effective for the prevention of cardiovascular events in patients with stable coronary disease.
本研究旨在确定每日服用 0.5 毫克秋水仙碱能否降低临床稳定型冠心病患者发生心血管事件的风险。
不稳定型冠心病患者的罪犯动脉粥样硬化斑块中存在活化的中性粒细胞，这提示秋水仙碱抑制中性粒细胞功能可能会降低斑块不稳定的风险，从而改善稳定型冠心病患者的临床结局。
在一项前瞻性、随机、观察者设盲终点设计的临床试验中，532 例正在服用阿司匹林和/或氯吡格雷（93%）和他汀类药物（95%）的稳定型冠心病患者被随机分为秋水仙碱 0.5 毫克/天组或不服用秋水仙碱组，并中位随访 3 年。主要终点是急性冠状动脉综合征、院外心脏骤停或非心源性缺血性卒中的复合发生率。主要分析为意向治疗分析。
在服用秋水仙碱的 282 例患者中有 15 例（5.3%）和未服用秋水仙碱的 250 例患者中有 40 例（16.0%）发生了主要终点事件（风险比：0.33；95%置信区间 [CI]：0.18 至 0.59；p<0.001；需要治疗的人数：11）。在预先设定的次要治疗分析中，排除了 32 例（11%）因肠道不耐受而在 30 天内停用秋水仙碱的患者和另外 7 例（2%）未开始治疗的患者，主要终点事件发生率分别为 4.5%和 16.0%（风险比：0.29；95% CI：0.15 至 0.56；p<0.001）。
在他汀类药物和其他标准二级预防治疗的基础上加用秋水仙碱 0.5 毫克/天似乎可有效预防稳定型冠心病患者的心血管事件。
