Supplementary Material for: Age-Dependent Impact of Medication Underuse and Strategies for Improvement

<b><i>Background:</i></b> Medication underuse is common in aging populations and, because of the growing risk for competing deaths, the benefit of preventive medicines gradually vanishes with advancing age, thus limiting their success. <b><i>Objective:</i></b> To estimate the optimum time of initiation of the secondary prevention of cardiovascular events, we examined the impact of appropriate pharmacotherapy for different starting ages at which it is implemented. <b><i>Methods:</i></b> In the competing risk framework, we obtained the population's life course from life tables, combined it with effect estimates quantifying the real-world effectiveness of secondary prevention, and compared the outcome of patients not receiving appropriate treatment (underuse) with those receiving preventive medicines that have demonstrated a reduction in the transition to serious cardiovascular events (START criteria). Starting at the age of 55 years, the population proportions of the distinct states of the framework were calculated for each year of chronological age in subgroups of appropriate treatment and underuse. These proportions were used over a follow-up period to estimate measures of treatment effectiveness and risks of underuse. <b><i>Results:</i></b> Despite increasing relative effectiveness with advancing age, benefits measured by patient-relevant endpoints, such as life years gained (LYG) or gained quality-adjusted life years (QALYs), markedly dropped after the starting age of 75 years, but even at an initiation age of 85 years, QALYs gained exceeded 1 year. <b><i>Conclusion:</i></b> Interventions targeting medication underuse may achieve considerable benefits at any stage of later life, while the benefit is probably largest if appropriate treatment is started before 75 years.

**背景：** 老年人群普遍存在药物使用不足的问题；由于竞争性死亡风险随年龄增长不断升高，预防性药物的获益会随年龄推进逐渐衰减，从而限制了其临床应用成效。
**目的：** 为明确心血管事件二级预防的最佳启动时机，本研究针对不同启动年龄下规范药物治疗的干预效果展开评估，以量化其影响。
**方法：** 本研究采用竞争风险框架，从生命表中获取人群生命历程数据，并结合量化二级预防真实世界有效性的效应估计值；同时将未接受规范治疗（药物使用不足）患者的转归与接受预防性药物、且已证实可降低严重心血管事件进展风险的患者（符合START标准）进行对比。以55岁为起始年龄，分别在规范治疗与药物使用不足两个亚组中，按每一岁实际年龄计算该框架下不同状态的人群占比。随后在随访周期内利用这些占比数据，估算治疗有效性指标与药物使用不足的风险。
**结果：** 尽管相对有效性随年龄增长而提升，但以患者相关终点（如获得生命年（life years gained, LYG）、质量调整生命年（quality-adjusted life years, QALYs））衡量的获益，在启动年龄超过75岁后会显著下降；即便在85岁启动治疗，获得的质量调整生命年仍可超过1年。
**结论：** 针对药物使用不足的干预措施，在老年阶段的任一时期均可带来可观获益；但若能在75岁前启动规范治疗，获益或可达最大。