Detection of a Novel Safety Signal for Atorvastatin Potential Association With Hilar Lymphadenopathy Using FAERS Disproportionality Analysis and Molecular Docking
Author(s)
Rithiksha V, Jr., MPH1, Eswaran Maheswari, Sr., PhD2, RAVINANDAN A P, M Pharm3, Sneha Anthony Zalki, MPH4.
1Pharmacy Practice, M S Ramaiah University of Applied Sciences, Bengaluru, India, 2Pharmacy Practice, M S Ramaiah University of Applied Sciences, Bangalore, India, 3Pharmacy Practice, MSRUAS, Bangalore, India, 4Ramaiah University of Applied Sciences, Bengaluru, India.
1Pharmacy Practice, M S Ramaiah University of Applied Sciences, Bengaluru, India, 2Pharmacy Practice, M S Ramaiah University of Applied Sciences, Bangalore, India, 3Pharmacy Practice, MSRUAS, Bangalore, India, 4Ramaiah University of Applied Sciences, Bengaluru, India.
OBJECTIVES: Atorvastatin is widely prescribed lipid-lowering agent used primarily in the treatment of hyperlipidemia and the prevention of cardiovascular diseases. It exerts its therapeutic effect by inhibiting HMG-CoA reductase, the rate-limiting enzyme in cholesterol biosynthesis, thereby lowering LDL cholesterol and reducing cardiovascular risk. This study aims to investigate a potential signal of atorvastatin using data mining approaches. To identify novel adverse signals of atorvastatin, focusing on its potential association with hilar lymphadenopathy using the FAERS database.
METHODS: An in-depth case/non-case retrospective disproportionality analysis was conducted using the publicly available FAERS database. Atorvastatin was approved by FDA in the 1996. The investigation delved into the USFDA adverse event reporting system database, employing the two widely accepted data mining algorithms in widespread use for signal detection such as Reporting Odds Ratio (ROR) and Proportional Reporting Ratio (PRR) from the OpenVigil database. A value of PRR≥1 and ROR-1.96SE>1 was considered as positive signal. The gene targets were identified using genecards, huge navigator, pubmed and omim databases. The autodock vina was used to determine the binding affinity of atorvastatin with the genes.
RESULTS: Among 30,668,520 reports in the FAERS database, 91,244 were associated with atorvastatin, including 9,752 classified as serious or life-threatening, with 4 cases specifically reporting hilar lymphadenopathy. Disproportionality analysis yielded a Reporting Odds Ratio (ROR) and Proportional Reporting Ratio (PRR) of 1.972, indicating a potential safety signal. These findings suggest a possible association between atorvastatin and hilar lymphadenopathy. The genes with the binding affinities are 2VX3, 8K5W with -8.9 and -6.9 respectively
CONCLUSIONS: Healthcare professionals should monitor for hilar lymphadenopathy as potential adverse reaction of atorvastatin. Further epidemiological studies are recommended to validate this novel signal in larger population.
METHODS: An in-depth case/non-case retrospective disproportionality analysis was conducted using the publicly available FAERS database. Atorvastatin was approved by FDA in the 1996. The investigation delved into the USFDA adverse event reporting system database, employing the two widely accepted data mining algorithms in widespread use for signal detection such as Reporting Odds Ratio (ROR) and Proportional Reporting Ratio (PRR) from the OpenVigil database. A value of PRR≥1 and ROR-1.96SE>1 was considered as positive signal. The gene targets were identified using genecards, huge navigator, pubmed and omim databases. The autodock vina was used to determine the binding affinity of atorvastatin with the genes.
RESULTS: Among 30,668,520 reports in the FAERS database, 91,244 were associated with atorvastatin, including 9,752 classified as serious or life-threatening, with 4 cases specifically reporting hilar lymphadenopathy. Disproportionality analysis yielded a Reporting Odds Ratio (ROR) and Proportional Reporting Ratio (PRR) of 1.972, indicating a potential safety signal. These findings suggest a possible association between atorvastatin and hilar lymphadenopathy. The genes with the binding affinities are 2VX3, 8K5W with -8.9 and -6.9 respectively
CONCLUSIONS: Healthcare professionals should monitor for hilar lymphadenopathy as potential adverse reaction of atorvastatin. Further epidemiological studies are recommended to validate this novel signal in larger population.
Conference/Value in Health Info
2025-11, ISPOR Europe 2025, Glasgow, Scotland
Value in Health, Volume 28, Issue S2
Code
RWD58
Topic
Clinical Outcomes, Epidemiology & Public Health, Real World Data & Information Systems
Topic Subcategory
Distributed Data & Research Networks
Disease
Cardiovascular Disorders (including MI, Stroke, Circulatory), Systemic Disorders/Conditions (Anesthesia, Auto-Immune Disorders (n.e.c.), Hematological Disorders (non-oncologic), Pain)