Cardiovascular Epidemiology Research Centre, University of Western Australia, Perth, Australia; School of Population and Global Health, University of Western Australia, Perth, Australia.
Heart and Vascular Research Institute, Harry Perkins Institute of Medical Research, Perth, Australia.
Am Heart J. 2024 Dec;278:186-194. doi: 10.1016/j.ahj.2024.09.006. Epub 2024 Sep 21.
The Low Dose Colchicine 2 (LoDoCo2) trial randomized 5,522 patients with chronic coronary disease to colchicine 0.5mg daily or placebo in a 1:1 ratio and demonstrated the cardiovascular benefits of colchicine. In the trial, which was conducted in Australia and The Netherlands, a prespecified subgroup analysis suggested a difference in magnitude of treatment effect of colchicine by region (Australia: HR 0.51; 95% CI 0.39-0.67 vs The Netherlands: HR 0.92; 95% CI 0.71-1.20). The aim of this study was to explore possible explanations for the apparent difference in magnitude of treatment effect of colchicine by region in the LoDoCo2 trial.
The analysis explored potential determinants of variations in the magnitude of effectiveness of colchicine treatment across the regions. This included investigating differences in investigational product, clinical characteristics, concurrent medical therapies and the duration of follow-up using a range of statistical techniques, including sub-group, landmark and effect modification analyses.
No differences were found in the colchicine product used in each region. Despite minor differences observed in baseline clinical characteristics and concomitant therapies, the effect modifier analyses demonstrated that these factors did not explain the difference in magnitude of treatment effect of colchicine by region. Randomization in Australia began more than 2 years before The Netherlands, with shorter duration of follow-up in The Netherlands compared to Australia. In a landmark analysis, over the period when more than 90% of patients in each region had been followed, the effects of colchicine were similar (Australia hazard ratio [HR] 0.58; 95% CI 0.34-0.97 vs The Netherlands HR 0.67; 95% CI 0.47-0.96).
After examining several plausible explanations for the observed differences in the magnitude of treatment effect of colchicine between regions in the LoDoCo2 trial could be due to the differences in duration of follow-up but a substantial portion of the differences remain unexplained.
低剂量秋水仙碱 2 号（LoDoCo2）试验将 5522 例慢性冠状动脉疾病患者随机分为秋水仙碱 0.5mg 每日组和安慰剂组，1:1 比例，结果显示秋水仙碱具有心血管获益。在该试验中，在澳大利亚和荷兰进行，预先设定的亚组分析表明，秋水仙碱的治疗效果因地区而异（澳大利亚：HR 0.51；95%CI 0.39-0.67 与荷兰：HR 0.92；95%CI 0.71-1.20）。本研究旨在探讨 LoDoCo2 试验中地区间秋水仙碱治疗效果大小差异的可能解释。
该分析探讨了影响秋水仙碱治疗效果大小的潜在决定因素。这包括使用一系列统计技术，包括亚组、标志和效应修饰分析，调查研究产品、临床特征、同时进行的医学治疗以及随访时间的差异，以探索秋水仙碱治疗效果大小在不同地区的差异。
在每个地区使用的秋水仙碱产品没有差异。尽管在基线临床特征和同时进行的治疗方面存在细微差异，但效应修饰分析表明，这些因素并不能解释地区间秋水仙碱治疗效果大小的差异。澳大利亚的随机分组比荷兰早了两年多，荷兰的随访时间比澳大利亚短。在标志分析中，当每个地区的超过 90%的患者随访超过一定时间时，秋水仙碱的效果相似（澳大利亚风险比[HR]0.58；95%CI 0.34-0.97 与荷兰 HR 0.67；95%CI 0.47-0.96）。
在对 LoDoCo2 试验中观察到的秋水仙碱治疗效果大小在地区间的差异进行了几种可能的解释后，可能是由于随访时间的差异，但仍有很大一部分差异未得到解释。
