Real-World Effectiveness of Lipid-Lowering Medications on Outcomes after Stroke: Potential Implications of the New-User Design

Introduction: 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. Methods: 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). Results: 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). Conclusions: 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.