Bioinformatics and Disproportionality Analysis of Novel Signals of Atorvastatin Using US Food and Drug Administration Adverse Event Reporting System (FAERS) Database

OBJECTIVES: This study aims to identify a potential adverse event of atorvastatin using data-mining algorithms and molecular docking.

METHODS: Various adverse events reported in FAERS database from 1996 to 2024 were analyzed to identify atorvastatin-related complications. The disproportionality analysis was conducted using OpenVigil 2 software package designed for complete data analysis. The data-mining algorithms like Reporting Odds Ratio (ROR) and Proportional Reporting Ratio (PRR) were used. The signal is considered positive if n>2 (Adverse event of interest), chisq>4 and PRR>2. The genes associated with new signals were identified by literature review and docked with atorvastatin using soft wares such as BIOVIA discovery studio, Swiss PDB viewer, PyRx and Pymol.

RESULTS: A total of 41,864 ADRs have been reported with atorvastatin from 1997 to June 2024. Approximately 12.8 % (5,397) and 4.01 % (1,678) of the cases were reported in 2023 and 2024 respectively. The ROR and PRR values were found to be 7.76 (2.464; 24.47). The Yate-corrected chi-square value was 11.22 confirming a positive case for biliary cirrhosis. The genes of human leukocyte antigen locus, HLA-DRB 1 and non HLA CTLA-4 are associated with biliary cirrhosis. Docking of HLA-DRB 1 and CLTA-4 with atorvastatin revealed the binding affinity of –7.9 and –7.7 respectively.

CONCLUSIONS: A total of 41,864 ADRs have been reported with atorvastatin from 1997 to June 2024. Approximately 12.8 % (5,397) and 4.01 % (1,678) of the cases were reported in 2023 and 2024 respectively. The ROR and PRR values were found to be 7.76 (2.464; 24.47). The Yate-corrected chi-square value was 11.22 confirming a positive case for biliary cirrhosis. The genes of human leukocyte antigen locus, HLA-DRB 1 and non HLA CTLA-4 are associated with biliary cirrhosis. Docking of HLA-DRB 1 and CLTA-4 with atorvastatin revealed the binding affinity of –7.9 and –7.7 respectively.