(B-295) NSAIDs and Gastrointestinal Bleeding: A Comprehensive Meta-Analysis of Individual Drug Risks

Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) are associated with a risk of upper gastrointestinal bleeding (GIB). However, the literature often categorizes NSAIDs as a homogeneous drug class, overlooking the significant heterogeneity in GIB risk between individual agents. This oversimplification may lead to suboptimal clinical decisions, particularly in patients who need pain relief but are at high risk for GIB.

Objectives: To evaluate the GIB risk associated with specific NSAIDs among users.

Methods: A comprehensive literature search was conducted using PubMed to identify relevant studies. Nine products (celecoxib, diclofenac, ibuprofen, indomethacin, ketoprofen, ketorolac, meloxicam, naproxen, and piroxicam) were combined with search terms for "gastrointestinal bleeding" and the MeSH term "hemorrhage." Studies were included if they reported results specific to GIB and provided relative risk (RR), odds ratio (OR), hazard ratio (HR), and/or the number of events/observations. Articles that assessed NSAIDs as a composite class without specific risk estimates for individual drugs were excluded. A random-effects model was used to synthesize the data.

Results: A total of 6,711 records were identified via PubMed. After removing duplicate records and other reasons such as animal studies, commentary, and case studies, 4,075 records were screened. Of these, 3,927 records were excluded. Following a detailed review of 99 reports, 26 studies fulfilled the inclusion criteria, comprising 19 case-control studies, 4 cohort studies, and 3 meta-analyses.
There was substantial variability in GIB risk among individual NSAIDs. Ketorolac exhibited the greatest risk, with a pooled OR 20.67 (95% CI: 11.82–36.13). Piroxicam followed with an OR of 9.30 (95% CI: 6.55–13.20). Meloxicam had a pooled OR of 6.85 (95% CI: 3.76–12.50), and indomethacin had an OR of 5.45 (95% CI: 4.52–6.57). Ketoprofen and naproxen exhibited similar risks, with pooled ORs of 4.82 (95% CI: 3.28–7.08) and 4.32 (95% CI: 3.30–5.66), respectively. Diclofenac’s OR was 3.44 (95% CI: 2.59–4.58). Among non-selective NSAIDs, ibuprofen had an OR of 2.28 (95% CI: 1.73–2.99). Lastly, celecoxib, a selective COX-2 inhibitor, had a pooled OR of 1.04 (95% CI: 0.77–1.41).

Conclusions: There is variability in GIB risk between NSAIDs, with celecoxib having no evidence of increased risk, while ketorolac and piroxicam have estimated odds greater than 9-fold. Even medications that are available over-the-counter (ibuprofen and naproxen) have significant risks of GIB.