Introduction: Nonsteroidal anti-inflammatory drugs (NSAIDs) and aspirin are commonly used together, yet the safety of this is uncertain.
Methods: In this analysis of the PRECISION trial on-treatment population, patients with NSAID-dependent arthritis at increased cardiovascular (CV) risk were treated with celecoxib, naproxen, or ibuprofen. Endpoints were a composite of major adverse cardiovascular events (MACE) (CV death, myocardial infarction, stroke, hospitalization for unstable angina or transient ischemic attack), non-CV death, gastrointestinal (GI), and renal events, as well as components of the composite. Outcomes were compared among drugs in presence or absence of aspirin by multivariable Cox proportional hazards models with a robust variance estimator.
Results: Of the 23,953 patients analyzed, 11,018 (46.0%) were on aspirin. In absence of aspirin, naproxen and ibuprofen were associated with greater risk of the composite endpoint compared to celecoxib (hazard ratio [HR] 1.52, 95% confidence interval [CI] 1.22-1.90, P<0.001 and HR 1.81, 95% CI 1.46-2.26, P<0.001; respectively). Compared to celecoxib, ibuprofen had higher MACE (P<0.05) and both ibuprofen and naproxen had higher GI (P<0.001) and renal (P<0.05) events. Among aspirin users, ibuprofen had greater risk of the composite endpoint compared to celecoxib (HR 1.27, 95% CI 1.06-1.51, P<0.01) while excess risk with naproxen was marginal (HR 1.18, 95% CI 0.98-1.41, P=0.08). There was no difference in MACE among NSAIDs. Compared to celecoxib, ibuprofen had higher GI and renal events (P<0.05) and naproxen had higher GI events (P<0.05) with no difference in renal events.
Conclusions: Celecoxib is associated with a more favorable overall safety profile compared to naproxen or ibuprofen in absence of aspirin. The addition of aspirin attenuates the safety advantage of celecoxib, although celecoxib is still associated with fewer GI events than ibuprofen or naproxen and fewer renal events than ibuprofen.