Integrating pharmacovigilance signals with real-world validation: a study on neurological events associated with...

Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are novel drugs widely used in clinical practice for the treatment of dyslipidemia. However, real-world data regarding their long-term neurological safety and tolerability in large populations remain incomplete. Therefore, we utilized the FAERS and real-world data from Chinese patients to jointly analyze the association between PCSK9 inhibitors and adverse drug events (ADEs) related to nervous system disorders.

A disproportionality analysis was performed on all ADEs associated with PCSK9 inhibitors in the FAERS database from the third quarter of 2015 to the second quarter of 2025. The reporting odds ratio (ROR) and Bayesian confidence propagation neural network (BCPNN) methods were employed to comprehensively evaluate and screen for statistically significant positive signals of adverse drug reactions related to nervous system disorders. These signals were further validated using follow-up data from 1,203 Chinese coronary heart disease (CHD) patients treated with PCSK9 inhibitors.

A total of 173,622 reports involving at least one PCSK9 inhibitor were identified in FAERS. Statistically significant positive ADEs signals associated with PCSK9 inhibitors included: Memory Impairment [n = 1,346, ROR = 1.48 (95% CI 1.4-1.56), IC = 0.55 (IC025 0.47), Bonferroni-p = 2.2028e^-42], Amnesia [n = 452, ROR = 1.25 (95% CI 1.14-1.38), IC = 0.32 (IC025 0.18), Bonferroni-p = 0.0097], Head Discomfort [n = 190, ROR = 1.46 (95% CI 1.26-1.68), IC = 0.54 (IC025 0.32), Bonferroni-p = 0.0013], Sinus Headache [n = 65, ROR = 2.38 (95% CI 1.86-3.04), IC = 1.23 (IC025 0.84), Bonferroni-p = 1.0944e^-08], and Carotid Artery Occlusion [n = 56, ROR = 3.08 (95% CI 2.36-4.02), IC = 1.59 (IC025 1.16), Bonferroni-p = 3.2089e^-14]. Analysis of real-world follow-up data from Chinese CHD patients revealed that, compared to CHD patients not using any PCSK9 inhibitors, those treated with PCSK9 inhibitors exhibited significantly higher incidences of Memory Impairment (p < 0.0001) and Head Discomfort (p = 0.0027).

Our study highlights that it is essential to recognize the potential risks of adverse neurological reactions, particularly Memory Impairment and Head Discomfort. These findings may assist healthcare professionals in providing more precise and individualized treatment plans.