SOURCE: Chan FKL, Ching JYL, Tse YK, et al. Lancet 2017;389:2375-2382.

Gastrointestinal bleeding (upper and/or lower) is a well-recognized adverse effect of aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs). The COX-2 inhibitors (e.g., celecoxib) were offered to clinicians as an alternative to “non-selective” COX inhibitors (NSAIDs such as ibuprofen, diclofenac, naproxen, and many others). The putative advantage of celecoxib was an anticipated reduced risk of gastrointestinal bleeding, since relatively less COX-1 (the enzyme necessary to maintain gastric mucosal protection integrity) inhibition was occurring than with “traditional” non-selective NSAIDs. While the CLASS trial corroborated that during a six-month period, celecoxib incurred fewer serious bleeding events than non-selective NSAID therapy. This trial drew criticism later after an analysis of the study data at one year showed no meaningful differences between treatment arms.

Patients who have experienced a gastrointestinal bleed on NSAIDs are at particularly high risk to bleed again. Additionally, concern about cardiovascular risks associated with NSAIDs becomes problematic for our vasculopathic patients (post-stroke, myocardial infarction, stenting, etc.) who require antiplatelet treatment (e.g., clopidogrel, aspirin). Nonetheless, many such patients require both antiplatelet and NSAID treatment concomitantly. Chan et al reported on their double-blind study of Helicobacter-negative subjects (n = 514) randomized to celecoxib or naproxen, all of whom had experienced and resolved an episode of upper gastrointestinal bleeding. Because of prior cardiovascular events, all subjects also were taking 80 mg of aspirin per day.

At 18 months, there was a clear advantage to the celecoxib/aspirin group vs. naproxen/aspirin: 5.6% cumulative bleeding events for the former vs. 12.3% for the latter. Persons who have experienced an NSAID-related upper gastrointestinal bleed would be better served by taking celecoxib than naproxen if continuation of NSAID treatment is required.