COMPARATIVE EFFECTIVENESS OF STATINS COMBINED WITH EZETIMIBE VERSUS STATINS COMBINED WITH PCSK9 INHIBITORS ON CARDIOVASCULAR AND COGNITIVE OUTCOMES: A PROPENSITY SCORE-MATCHED ANALYSIS

Abstract

Pharmacologic Therapy While both ezetimibe and PCSK9 inhibitors are used as adjunct therapies to statins for lipid management, real-world comparative data on their impact on cardiovascular and cognitive outcomes remain limited. This retrospective cohort study aimed to evaluate the effectiveness of statin+ezetimibe versus statin+PCSK9 combinations. Using the TriNetX platform, we analyzed data from patients receiving statin+ezetimibe (n=149,933) and statin+PCSK9 (n=8,060). After propensity score matching across 23 variables, 8,059 patients remained in each group. Outcomes assessed included cognitive impairment and dementia, ischemic stroke, atherosclerosis of coronary arteries, mortality, and LDL cholesterol levels. Cox regression analysis was used to estimate hazard ratios (HR) with 95% confidence intervals (CIs). Over a median follow-up of approximately 592 days for statin+ezetimibe and 465 days for statin+PCSK9 cohorts, the statin+ezetimibe group showed higher risks of cognitive impairment and dementia (HR 1.49, 95% CI 1.12–1.97, p =0.005) and mortality (HR 1.15, 95% CI 1.01–1.32, p=0.04). No significant differences were observed in ischemic stroke risk. However, the statin+ezetimibe group showed a lower risk of atherosclerosis of coronary arteries (HR 0.68, 95% CI 0.59–0.79, p <0.001). LDL levels were modestly lower in the statin+PCSK9 group (76.5 ± 49.1 mg/dL vs. 83.2 ± 43.3 mg/dL, p <0.001). This propensity score-matched analysis suggests that combining PCSK9 inhibitors with statins may confer advantages in reducing risks of cognitive decline and mortality compared to the statin+ezetimibe regimen, alongside improved LDL control. However, the statin+ezetimibe group demonstrated a lower incidence of coronary artery atherosclerosis.