Yeh Yi-Chun, Chen Yen-Yu, Chen Pei-Chun
Department of Public Health, China Medical University, Taichung, Taiwan; Research Education and Epidemiology Center, Changhua Christian Hospital, Changhua, Taiwan.
Research Education and Epidemiology Center, Changhua Christian Hospital, Changhua, Taiwan; Department of Neurology, Changhua Christian Hospital, Changhua, Taiwan.
J Clin Epidemiol. 2022 Oct;150:98-105. doi: 10.1016/j.jclinepi.2022.06.014. Epub 2022 Jun 30.
We examined the association between statin use and hepatocellular carcinoma (HCC) incidence in patients with diabetes using marginal structural models (MSMs) estimated by inverse probability weight (IPW), which adjusts for time-varying confounders that are also mediators, and we compared the results with conventional regression methods.
This retrospective cohort study included 245,122 patients with type 2 diabetes who were new users of lipid-lowering drugs identified using the claims data of a universal health insurance program. Statin exposure was time-updated every three months during the follow-up period. Stabilized IPW was calculated and accounted for chronic liver diseases considering as time-dependent confounders affected by past statin exposure.
Over a median follow-up of 5.2 years, 1,694 patients developed HCC. In the conventional regression analysis, the hazard ratio of HCC associated with statin use was 0.88 (95% confidence interval CI: 0.79-0.97) after adjusting for baseline covariates and 0.97 (95% CI: 0.87-1.08) after additionally adjusting for time-varying covariates. The hazard ratio increased to 1.11 (95% CI: 0.94-1.31) using the MSM approach.
Statin use was not associated with the risk of developing HCC in patients with diabetes. Our findings highlight the importance of controlling time-varying confounders in observational studies.
我们使用逆概率加权法（IPW）估计的边际结构模型（MSM），研究了糖尿病患者使用他汀类药物与肝细胞癌（HCC）发病率之间的关联，该模型可对同时作为中介因素的随时间变化的混杂因素进行调整，并将结果与传统回归方法进行比较。
这项回顾性队列研究纳入了245122例2型糖尿病患者，这些患者是通过一项全民健康保险计划的理赔数据确定的降脂药物新使用者。在随访期间，他汀类药物暴露情况每三个月更新一次。计算稳定的IPW，并将慢性肝病视为受既往他汀类药物暴露影响的随时间变化的混杂因素进行考虑。
在中位随访5.2年期间，1694例患者发生了HCC。在传统回归分析中，调整基线协变量后，使用他汀类药物与HCC相关的风险比为0.88（95%置信区间CI：0.79-0.97），额外调整随时间变化的协变量后为0.97（95%CI：0.87-1.08）。使用MSM方法时，风险比增至1.11（95%CI：0.94-1.31）。
糖尿病患者使用他汀类药物与发生HCC的风险无关。我们的研究结果突出了在观察性研究中控制随时间变化的混杂因素的重要性。
