Gastrointestinal Complications of Over-the-Counter Non-Steroidal Anti-Inflammatory Drugs

Abstract

Purpose: This study assessed the risk for perforations, ulcers and bleeds (PUBs) in a US representative population using OTC dosage strengths of naproxen or ibuprofen with or without concomitant aspirin in a real world setting. Methods: A retrospective review of an electronic medical record (EMR) database containing the ambulatory health record data for over 3.2 million individuals was conducted. Subjects were eligible for inclusion in the study if they received naproxen (220 mg) or ibuprofen (200 mg). An index date for each subject was defined as the first mention of an OTC NSAID in the dataset. Exclusion criteria: concomitant oral steroid usage, concomitant coumadin usage, or any of the following co-morbid conditions: infectious diseases, GI cancers, enteritis, colitis and diverticula of the intestines. The dataset was analyzed for concomitant aspirin use and PUBs. A pre-/post analysis was conducted using a case-crossover design with subjects as their own controls. The index date was the defining event, in order to determine the odds ratio associated with OTC NSAID usage. Two different pre-index time periods were evaluated for PUBs, 180 and 365 days. For the post-index time period, only PUBs that occurred within 90 days of the OTC NSAID entry in the EMR dataset were considered. Results: The dataset contained 11,957 subjects on naproxen and 38,507 subjects on ibuprofen. In all cases, OTC NSAID usage was associated with a statistically significant increase in the odds ratio for PUBs. The concomitant aspirin population consisted of 2,328 naproxen subjects and 4,843 ibuprofen subjects. In both cases, concomitant aspirin usage was associated with a significantly higher risk for PUBs than the corresponding monotherapy. Subjects taking both ibuprofen and aspirin had an odds ratio of 3.36 (2.36 – 4.80, p < 0.00001), while those on naproxen and aspirin had an odds ratio of 2.07 (1.23 − 3.49, p = 0.005) relative to those subjects on ibuprofen and naproxen monotherapy, respectively. Conclusions: Even at OTC doses, ibuprofen and naproxen are associated with increased risk of serious GI events. Concomitant aspirin use can significantly increase such risk.Table: OTC NSAIDs' Odds Ratio for PUBs