Abstract TH928: Sequence Symmetry Analysis Shows Cardiovascular Safety Signals Associated with Non-Steroidal Anti-Inflammatory Drugs

Abstract

Background: Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly prescribed for pain, inflammation, and fever; however, real-world evidence on the cardiovascular risks of individual NSAIDs remains limited. Sequence symmetry analysis (SSA) is a signal detection method for identifying adverse drug events (ADEs) in large electronic health record datasets. This study applied SSA to identify cardiovascular ADE signals associated with oral NSAIDs. Methods: This cohort study used primary care records from the UK Clinical Practice Research Datalink (CPRD GOLD). Adults ≥18 years with ≥1 year of prior observation and a new NSAID prescription between 2013-2023 were included. Incidence of seven cardiovascular events (acute myocardial infarction [MI], arrhythmia, deep vein thrombosis [DVT], heart failure, hemorrhagic stroke, ischemic stroke, pulmonary embolism [PE]) was assessed within 180 days before versus after NSAID initiation. Adjusted sequence ratios (aSR) with 95% confidence intervals were calculated for each NSAID-event pair, with aSR>1 indicating a positive ADE signal and aSR<1 indicating protective effect. Positive (NSAID-edema) and negative (NSAID-cataract) controls assessed validity. Sensitivity analyses included stratification by age and sex, alternate windows (90 and 365 days), and stratification by prior proton pump inhibitor (PPI) use. Results: 77,570 patients met inclusion criteria (median age 66 [IQR 54-76]; 53.9% male). Positive and negative controls aligned with expectations. Naproxen showed positive signals across all events, with the highest for PE (3.03 [2.63-3.51]). Ibuprofen showed six positive signals, with PE being highest (2.2 [1.88-2.59]). Diclofenac and etoricoxib each had five positive signals, with MI (3.30 [2.42-4.57]) and ischemic stroke (3.84 [2.11-7.43]) as the highest, respectively. Celecoxib and meloxicam showed four positive signals, with the highest being heart failure (2.15 [1.17-4.11]) and PE (2.66 [1.30-5.82]), respectively. MI and arrhythmia were common across all aforementioned medications. Aspirin showed negative signals across all events except PE (1.08 [0.96-1.22]). Age, sex, and window sensitivity analyses were consistent, while prior PPI stratification showed aSR attenuation in prior users. Conclusions: Individual NSAIDs exhibit varied cardiovascular ADE signals, underscoring the need for personalized risk evaluation. SSA in real-world data enhances pharmacovigilance by identifying rare ADE trends.