Cardiovascular risk of selective cyclooxygenase‐2 inhibitors and other non‐aspirin non‐steroidal anti‐inflammatory medications

PURPOSE: The purpose of this study was to estimate rates of acute coronary syndrome (ACS), and sudden cardiac death in relation to use of rofecoxib, celecoxib, naproxen, diclofenac, and ibuprofen. METHODS: We conducted a retrospective cohort study among 424,584 health plan enrollees ages 40-64 who used non-aspirin non-steroidal anti-inflammatory drugs (NANSAIDs) by prescription from 1999 to 2001. We used automated medical and pharmacy claims data to compute person-time exposed to study drugs, and to identify hospitalizations for ACS. The primary endpoint was ACS, inclusive of myocardial infarction (MI), unstable angina, and sudden cardiac death as identified through claims data and confirmed through hospital medical records, or through the National Death Index. RESULTS: Compared with ibuprofen or diclofenac use, the relative risk (RR) of ACS during periods of current rofecoxib use was 1.35 (95%CI 1.09-1.68). For current use of celecoxib, the RR was 1.03 (95%CI 0.83-1.27). Risks in the first 30 days of rofecoxib and celecoxib use were modestly elevated. Rofecoxib use at the 25 mg/day (modal) dose was associated with an elevated risk of ACS (RR 1.54, 95%CI 1.15-2.04), while use at 26-50 mg/day (>modal) was not (RR 0.81, 95%CI 0.41-1.60). There were no increased risks with modal or greater than modal doses of celecoxib or naproxen compared with all doses of ibuprofen or diclofenac combined. CONCLUSIONS: The incidence of ACS was 1.35 times greater during rofecoxib use than use of ibuprofen or diclofenac. No statistically significant elevation in risk was observed with celecoxib use. Naproxen use was not associated with risk of ACS.