Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors Induced Neurocognitive Disorder: A Pharmacovigilance Study by Analyzing the Data from the U.S. FDA Adverse Event Reporting System

Abstract

PurposeThe neurocognitive disorder is a rare adverse event associated with Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) inhibitors in the randomized controlled trail (RCTs), there was limited evidence to prove their relation. This study aimed to assessing their association by detecting adverse signal in the FDA Adverse Event Reporting System (FAERS).MethodsThe disproportionality analysis was conducted to detect the potential adverse signal between neurocognitive disorders and PCSK9 inhibitors. The adverse event reports from the first quarter of 2004 to the second quarter of 2020 were extracted from the FAERS database.ResultsThere were 81,272 adverse reports correlated with the usage of the PCSK9 inhibitors, of which 152 reports corresponded with our inclusion criteria. Among them, there were 106 and 46 neurocognitive disorder reports related to the usage of Evolocumab and Alirocumab, respectively. The total ROR value presented negative disproportionality, however, Alirocumab has generated a positive signal with a higher ROR value in comparison with Evolocumab. Moreover, there were 61.19% of adverse reports were submitted by healthcare professionals. As for the outcome events, 7.79% of patients had initial or prolonged hospitalization and 3.90% suffered a disability.ConclusionThe pharmacovigilance research helps to find out more about PCSK9 inhibitor-related neurocognitive disorders. Although the positive signal was identified in Alirocumab in this study, it still required further research to prove the association between neurocognitive disorder and PCSK9 inhibitors. In addition, the tenable mechanism should be explored, which can improve the insight of this neotype lipid-lowering medicine.