Département de médecine sociale et préventive, Université Laval, Québec, Canada; Centre de recherche du CHU de Québec, Université Laval, Québec, Canada.
Centre de recherche du CHU de Québec, Université Laval, Québec, Canada; Faculté de pharmacie, Université Laval, Québec, Canada; Institut national de santé publique du Québec, Québec, Canada.
J Clin Epidemiol. 2024 Apr;168:111284. doi: 10.1016/j.jclinepi.2024.111284. Epub 2024 Feb 15.
Evidence concerning the effect of statins in primary prevention of cardiovascular disease (CVD) among older adults is lacking. Using Quebec population-wide administrative data, we emulated a hypothetical randomized trial including older adults >65 years on April 1, 2013, with no CVD history and no statin use in the previous year.
We included individuals who initiated statins and classified them as exposed if they were using statin at least 3 months after initiation and nonexposed otherwise. We followed them until March 31, 2018. The primary outcome was the composite endpoint of coronary events (myocardial infarction, coronary bypass, and percutaneous coronary intervention), stroke, and all-cause mortality. The intention-to-treat (ITT) effect was estimated with adjusted Cox models and per-protocol effect with inverse probability of censoring weighting.
A total of 65,096 individuals were included (mean age = 71.0 ± 5.5, female = 55.0%) and 93.7% were exposed. Whereas we observed a reduction in the composite outcome (ITT-hazard ratio (HR) = 0.75; 95% CI: 0.68-0.83) and mortality (ITT-HR = 0.69; 95% CI: 0.61-0.77) among exposed, coronary events increased (ITT-HR = 1.46; 95% CI: 1.09-1.94). All multibias E-values were low indicating that the results were not robust to unmeasured confounding, selection, and misclassification biases simultaneously.
We cannot conclude on the effectiveness of statins in primary prevention of CVD among older adults. We caution that an in-depth reflection on sources of biases and careful interpretation of results are always required in observational studies.
关于他汀类药物在老年人一级预防心血管疾病（CVD）中的作用的证据尚缺乏。我们利用魁北克省全人群行政数据，模拟了一项假设性的随机试验，纳入了 2013 年 4 月 1 日年龄≥65 岁、无 CVD 病史且前一年未使用他汀类药物的老年人。
我们纳入了开始使用他汀类药物的个体，如果他们在开始使用他汀类药物至少 3 个月后仍在使用他汀类药物，则将其归类为暴露组，否则归类为非暴露组。我们对他们进行随访，直至 2018 年 3 月 31 日。主要结局是冠状动脉事件（心肌梗死、冠状动脉旁路移植术和经皮冠状动脉介入治疗）、卒中和全因死亡率的复合终点。意向治疗（ITT）效果采用调整后的 Cox 模型估计，方案意向治疗效果采用逆概率 censoring 加权估计。
共纳入 65096 名患者（平均年龄 71.0±5.5 岁，女性占 55.0%），其中 93.7%为暴露组。我们观察到暴露组的复合结局（ITT 风险比（HR）=0.75；95%CI：0.68-0.83）和死亡率（ITT-HR=0.69；95%CI：0.61-0.77）降低，但冠状动脉事件增加（ITT-HR=1.46；95%CI：1.09-1.94）。所有多偏倚 E 值均较低，表明结果不受未测量混杂、选择和分类偏倚的影响。
我们不能确定他汀类药物在老年人 CVD 一级预防中的有效性。我们警告说，在观察性研究中，始终需要对偏倚的来源进行深入反思，并对结果进行谨慎解释。
