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KMID : 1142220230180020183
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Regulatory Research on Food, Drug & Cosmetic
2023 Volume.18 No. 2 p.183 ~ p.192
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PCSK9 inhibitors and Cognitive Dysfunction related Adverse Events: A Pharmacovigilance Study Using the World Health Organization VibiBase
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Park Da-Hyun
Bea Sung-Ho
Bae Ji-Hwan
Lee Hye-Sung
Choe Young-June
Shin Ju-Young
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Abstract
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Protein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are novel lipid-lowering agents used in patients with cardiovascular diseases. Despite reassuring safety data from pivotal trials, increasing evidence from realworld studies suggests that PCSK9 inhibitors may increase the risk for cognitive dysfunction. This study aimed to identify signals of cognitive dysfunction-related adverse events (AEs) associated with PCSK9 inhibitors. We performed an observational pharmacovigilance study using the World Health Organization (WHO) VigiBase data up to December 2022. We included individual case safety reports (ICSRs) of the PCSK9 inhibitors alirocumab and evolocumab and compared them with those of other drugs. As the primary outcome, cognitive dysfunction was defined using the Medical Dictionary for Regulatory Activities (MedDRA) system’s High Level Group Term (HLGT) ‘Cognitive and attention disorders and disturbances’ and ‘Mental impairment disorders’ The secondary outcomes indicated specific classifications of cognitive dysfunction-related AEs. Among 114,293 reports (258,099 drug-AE pairs) on PCSK9 inhibitors, 8464 (31,951 drug-AE pairs) were identified as cognitive dysfunction-related AEs. Among the ICSRs, 54% included female patients, 41% persons aged ?65 years, and the majority (82%) were for those who received evolocumab. The study revealed a significant disproportionality for cognitive dysfunction with PCSK9 inhibitors(ROR 1.70, 95% CI 1.63-1.77). Specifically, significant signals were identified for cognitive disorder (ROR 1.47, 95% CI 1.28-1.69), memory impairment (ROR 2.72, 95% CI 2.56-2.88), and amnesia(ROR 1.50, 95% CI 1.36-1.65). This pharmacovigilance study identified an increased reporting of cognitive dysfunction associated with the use of PCSK9 inhibitors, particularly emphasizing caution regarding ‘memory abnormalities’ in elderly patients receiving PCSK9 inhibitors. Our findings support the need for the systematic surveillance of cognitive dysfunctions among PCSK9 inhibitor users.
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KEYWORD
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PCSK9 inhibitors, cognitive dysfunction, VigiBase, adverse events, Signal detection
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