Department of Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, Victoria, Australia.
Peninsula Clinical School, Central Clinical School, Monash University, Frankston, Victoria, Australia.
Neuroepidemiology. 2022;56(5):365-372. doi: 10.1159/000526071. Epub 2022 Jul 21.
Observational studies are increasingly being used to provide evidence on the real-world effectiveness of medications for preventing vascular diseases, such as stroke. We investigated whether the real-world effectiveness of treatment with lipid-lowering medications after ischemic stroke is affected by prevalent-user bias.
An observational cohort study of 90-day survivors of ischemic stroke using person-level data from the Australian Stroke Clinical Registry (2012-2016; 45 hospitals) linked to administrative (pharmaceutical, hospital, death) records. The use of, and adherence to (proportion of days covered <80% [poor adherence] vs. ≥80% [good adherence]), lipid-lowering medications within 90 days post-discharge was determined from pharmaceutical records. Users were further classified as prevalent (continuing) or new users, based on dispensing within 90 days prior to stroke. A propensity score-adjusted Cox regression was used to evaluate the effectiveness of lipid-lowering medications on outcomes (all-cause mortality, all-cause and cardiovascular disease readmission) within the subsequent year. Analyses were undertaken using prevalent-user (all users vs. nonusers) and new-user designs (new users vs. nonusers).
Of 11,217 eligible patients (median age 72 years, 42% female), 9,294 (83%) used lipid-lowering medications within 90 days post-discharge, including 5,479 new users. In both prevalent-user and new-user designs, nonusers (vs. users) had significantly greater rates of mortality (hazard ratio [HR] 2.35, 95% CI: 1.89-2.92) or all-cause readmissions (HR 1.22, 95% CI: 1.05-1.40) but not cardiovascular disease readmission. In contrast, associations between having poor (vs. good) adherence on outcomes were stronger among new users than all users. Among new users, having poor adherence was associated with greater rates of mortality (HR 1.48, 95% CI: 1.12-1.96), all-cause readmission (HR 1.14, 95% CI: 1.02-1.27), and cardiovascular disease readmission (HR 1.20, 95% CI: 1.01-1.42).
The real-world effectiveness of treatment with lipid-lowering medications after stroke is attenuated when evaluated based on prevalent-user rather than new-user design. These findings may have implications for designing studies on the real-world effectiveness of secondary prevention medications.
越来越多的观察性研究被用于提供关于药物预防血管疾病（如中风）的真实世界疗效的证据。我们研究了在缺血性中风后使用降脂药物的真实世界疗效是否受到普遍使用者偏倚的影响。
这是一项基于澳大利亚中风临床登记处（2012-2016 年；45 家医院）的个体水平数据的 90 天幸存者的观察性队列研究，该登记处与行政（药物、医院、死亡）记录相链接。通过药物记录确定出院后 90 天内使用和（或）遵医嘱使用（覆盖比例<80%[差]与≥80%[好]）降脂药物的情况。根据 90 天内中风前的配药情况，将使用者进一步分类为持续使用者（继续使用者）或新使用者。使用倾向评分调整的 Cox 回归来评估降脂药物在随后一年内对结局（全因死亡率、全因和心血管疾病再入院）的有效性。使用普遍使用者（所有使用者与非使用者）和新使用者设计（新使用者与非使用者）进行分析。
在 11217 名合格患者中（中位年龄 72 岁，42%为女性），9294 名（83%）患者在出院后 90 天内使用了降脂药物，其中 5479 名是新使用者。在普遍使用者和新使用者设计中，非使用者（与使用者相比）的死亡率（危险比 [HR] 2.35，95%置信区间 [CI]：1.89-2.92）或全因再入院率（HR 1.22，95%CI：1.05-1.40）均显著更高，但心血管疾病再入院率并无差异。相比之下，在新使用者中，药物不良依从（覆盖比例<80%）与结局的相关性强于所有使用者。在新使用者中，药物不良依从与更高的死亡率（HR 1.48，95%CI：1.12-1.96）、全因再入院（HR 1.14，95%CI：1.02-1.27）和心血管疾病再入院（HR 1.20，95%CI：1.01-1.42）相关。
根据普遍使用者而非新使用者设计评估，中风后使用降脂药物的真实世界疗效会减弱。这些发现可能对设计二级预防药物真实世界疗效的研究具有重要意义。
