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

Abstract

Pharmacologic Therapy Although evidence from randomized clinical trials supports the efficacy of combining proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors with statins in lipid management, there is limited real-world data on the long-term comparative outcomes. This retrospective study aims to compare the efficacy of these therapies. We conducted a retrospective cohort study using the TriNetX database, analyzing patients on statins alone (n=3,001,487) versus statins+PCSK9 inhibitors (n=7,686). Propensity score matching yielded balanced cohorts (n=7,684 each). Cox regression was used to calculate hazard ratios (HR) and 95% confidence intervals (CI). After propensity score matching, with a mean follow-up of 2.10 ± 1.72 years, statin monotherapy was significantly associated with an increased risk of adverse outcomes (figure), including cognitive impairment and dementia (HR 1.55, 95% CI 1.17–2.04) and mortality (HR 1.52, 95% CI 1.34–1.73). However, patients in the statin group had a lower risk of atherosclerosis of coronary arteries (HR 0.59, 95% CI 0.51–0.68). Additionally, LDL cholesterol levels were significantly lower in patients treated with the combination therapy compared to statins alone (6.7 ± 49.2 mg/dL vs. 81.3 ± 37.1 mg/dL, p<0.001). No statistically significant results were found for risk of ischemic stroke between groups. In this propensity-matched analysis, adding PCSK9 inhibitors to statin therapy was associated with significantly lower risks of cognitive impairment and dementia and mortality compared to statin monotherapy. Additionally, combination therapy was linked to improved LDL cholesterol control. However, patients on combination therapy showed a higher risk of coronary artery atherosclerosis, highlighting the complexity of treatment decisions and the need for individualized clinical strategies.