| アブストラクト | BACKGROUND: Atorvastatin, a widely prescribed HMG-CoA reductase inhibitor, is associated with neurological adverse events (NAEs) beyond its well-known myopathy; however, comprehensive evaluations accounting for confounding by indication remain limited. METHODS: A disproportionality analysis was performed using the FDA Adverse Event Reporting System (FAERS) database (Q1 2004-Q3 2025) with three signal detection algorithms (PRR, BCPNN, and MGPS). Signal criteria were: PRR >/= 2, chi(2) >/= 4, EBGM(05) > 2, IC(025) > 0. To minimize confounding by indication, reports with indications for hypercholesterolemia or coronary artery disease (i.e., the approved label indications of atorvastatin) were excluded. RESULTS: Of 50 NAE signals identified for atorvastatin, 32 remained significant after exclusion. The strongest signals clustered into three clinically meaningful categories: neuromuscular junction disorders (myasthenia gravis: PRR = 5.65, chi(2) = 748.22, EBGM(05) = 4.82), peripheral neuropathies (axonal neuropathy: PRR = 6.15, chi(2) = 117.78, EBGM(05) = 4.14; peripheral sensory neuropathy: PRR = 3.42, chi(2) = 182.34, EBGM(05) = 2.80), and central nervous system and cognitive disorders (encephalitis toxic: PRR = 7.76, chi(2) = 17.11, EBGM(05) = 2.39; brain fog: PRR = 2.94, chi(2) = 168.76, EBGM(05) = 2.46). Additionally, exceptionally strong signals without detailed published case support included acute necrotising myelitis (PRR = 832.92, EBGM(05) = 38.61), vibration syndrome (PRR = 37.02, EBGM(05) = 14.51), and radiculitis brachial (PRR = 26.03, EBGM(05) = 13.57). CONCLUSION: This study identified multiple strong neurological safety signals associated with atorvastatin using a rigorous disproportionality analysis with adjustment for confounding by indication. These findings provide valuable real-world evidence to guide clinical monitoring and warrant further validation. |
|---|
