Abstract
Purpose
PCSK9 might affect central nervous system development, neuronal apoptosis, and differentiation. We investigate the neurocognitive adverse events associated with the use of PCSK9 inhibitors (alirocumab and evolocumab) using pharmacovigilance reports.
Methods
We used the World Health Organization pharmacovigilance database (VigiBase) to perform a disproportionality analysis comparing the proportion of neurocognitive adverse events reported with PCSK9 inhibitors versus the proportion of these effects reported since August 14, 2015 (date of first post-marketing report suspecting a PCSK9 inhibitor), for all drugs in the database. Associations between PCSK9 inhibitor use and neurocognitive adverse events were assessed using both proportional reporting ratio (PRR) and information component (IC). Complementary analyses were performed on other neurologic events, and different sensitivity analyses were conducted to evaluate the robustness of results.
Results
Among the 81,108 reports involving at least one PCSK9 inhibitor, 1,941 concerned the occurrence of neurocognitive disorders. Most of patients (52.3%) were aged 45–74 years, and 58.0% were women. Signals of disproportionate reporting were found for PCSK9 inhibitors (PRR 1.22, 95% CI 1.17; 1.28; IC 0.28, IC025 0.21) and for each drug individually. No signal of disproportionality was found for any of the other neurologic events investigated. Signals of disproportionate reporting were found for the positive control (benzodiazepines), but not for the negative control (aspirin). The results of the main analysis were confirmed by sensitivity analyses.
Conclusions
This study identified a signal of neurocognitive disorders associated with PCSK9 inhibitors and encourages paying attention to at-risk populations.
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Data Availability
Not applicable.
Code Availability
Upon request to corresponding author.
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Acknowledgements
The authors would like to thank the Uppsala Monitoring Centre (UMC) that provided and gave permission to use the data analyzed in the present study. The authors are indebted to the French Regional Pharmacovigilance Centres that contributed data. The opinions and conclusions in this study do not necessarily reflect those of the regional centers or of the World Health Organization.
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Study designs were decided on by AG and JB. AG carried out data extraction and all analyses. AG and JB wrote the first draft. All authors contributed to further drafts and approved the final manuscript.
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Gouverneur, A., Sanchez-Pena, P., Veyrac, G. et al. Neurocognitive Disorders Associated with PCSK9 Inhibitors: a Pharmacovigilance Disproportionality Analysis. Cardiovasc Drugs Ther 37, 271–276 (2023). https://doi.org/10.1007/s10557-021-07242-7
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DOI: https://doi.org/10.1007/s10557-021-07242-7