Risk of ischaemic cardiovascular events from selective cyclooxygenase‐2 inhibitors in osteoarthritis

PURPOSE: Most previous observational studies assessing cardiovascular risk associated with Cox-2 inhibitors (Cox-2is) used a case control approach, limiting the assessment of absolute risk by disease group and effect of duration of exposure. We conducted a retrospective cohort study in patients with osteoarthritis. METHODS: Using the Life-link US claims database, all subjects had at least five years history in the database. Exposure was defined as the first chronic period of Cox-2i (celecoxib, rofecoxib or valdecoxib) or naproxen use. Non-users and non-chronic users of non-steroidal anti-inflammatory drug (NSAID)/Cox-2i within the osteoarthritis cohort served as the reference. The primary outcome was myocardial infarction and ischaemic stroke. RESULTS: A cohort of 16,580 subjects were chronically exposed to celecoxib, 9800 received rofecoxib, 2907 received naproxen and 51,539 were non-chronically exposed controls. With a median follow up of 506 days, there were 2116 ischaemic events for the entire cohort. The strongest predictors of AMI/ ischaemic stroke risk were history of ischaemic stroke (HR 2.34, 2.12-2.59) and age 65+ years (HR 2.28, 2.07-2.52). For rofecoxib, (HR 1.25,1.04-1.50), the attributable risk varied from 3 per 1000 patients years in individuals aged under 65 years with no history of CVD to 19 per 1000 patients years in older individuals with a history of CVD. The hazard ratios did not change over time. Celecoxib and naproxen were not associated with increased risks. CONCLUSIONS: The attributable risk for rofecoxib varied substantially with the underlying cardiovascular risk profile, being lower in clinical trial than in clinical practice populations.