Proactive Adverse Drug Event Signal Detection: A Self-Controlled Cohort Study of Elderly Atorvastatin Initiators

Purpose: Pharmacovigilance is essential for detecting adverse drug events (ADEs) not captured or adequately quantified in pre-approval trials. This study aimed to proactively detect ADE signals associated with atorvastatin initiation in elderly Medicare beneficiaries. Methods: : A self-controlled cohort study included patients ≥ 65 years with ≥ 12 months of Medicare enrollment before initiating atorvastatin during the observation period (2018–2019) – which was split into unexposed (pre-initiation) and exposed (post-initiation) phases. Among 900 outcomes evaluated, the first (incident) event was classified as either unexposed or exposed. ADE signals were identified if the incidence rate ratio (IRR) was ≥1.5, Z-score ≥1.96, and number needed to harm (NNH) was >0–1,000, comparing event rates before vs. after initiation. Results: : Among 690,004 Medicare beneficiaries, hepatic failure (HepF) and cardiac arrest/ventricular fibrillation (CA/VF) emerged as key ADE signals after atorvastatin initiation. An age-gradient was observed where 75–84-year-olds had a ~45% higher rate, while those 85+ faced over double the rate for both HepF and CA/VF; Black patients were also at significantly increased risk. For HepF, 298 patients aged 85+ and 320 Black patients needed to initiate atorvastatin to cause one case, while for CA/VF, 78 patients aged 85+ and 59 Black patients required the same to cause one case. Other ADE signals included mental health issues, bleeding disorders, and trauma-related events. Conclusion: This study highlights HepF and CA/VF as ADE risks associated with atorvastatin in elderly patients, emphasizing the importance of proactive real-world pharmacovigilance in this vulnerable population. Further research is needed to confirm these findings.