[Pubmed] Atorvastatin-associated neurological adverse events: a disproportionality analysis with adjustment for confound

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Front Med (Lausanne). 2026 Jul 7;13:1852942. doi: 10.3389/fmed.2026.1852942. eCollection 2026.

ABSTRACT

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, χ2 ≥ 4, EBGM05 > 2, IC025 > 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, χ2 = 748.22, EBGM05 = 4.82), peripheral neuropathies (axonal neuropathy: PRR = 6.15, χ2 = 117.78, EBGM05 = 4.14; peripheral sensory neuropathy: PRR = 3.42, χ2 = 182.34, EBGM05 = 2.80), and central nervous system and cognitive disorders (encephalitis toxic: PRR = 7.76, χ2 = 17.11, EBGM05 = 2.39; brain fog: PRR = 2.94, χ2 = 168.76, EBGM05 = 2.46). Additionally, exceptionally strong signals without detailed published case support included acute necrotising myelitis (PRR = 832.92, EBGM05 = 38.61), vibration syndrome (PRR = 37.02, EBGM05 = 14.51), and radiculitis brachial (PRR = 26.03, EBGM05 = 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.

PMID:42482918 | PMC:PMC13385032 | DOI:10.3389/fmed.2026.1852942


Source: https://pubmed.ncbi.nlm.nih.gov/4248291 ... 8&v=2.20.0