All-cause mortality of elderly Australian veterans using COX-2 selective or non-selective NSAIDs: a longitudinal study

Abstract

What is already known about this subject: • Previous studies have found varying impact of exposure to COX-2 selective and non-selective NSAIDs.

What this study adds: • Individuals receiving a COX-2 selective NSAID had an increased risk of all-cause mortality after correction for age, sex and cardiovascular risk as measured by co-prescription. • Despite differences in the pharmacokinetic properties of the COX-2 selective inhibitor drugs, our study lends no support to clinicians preferring any one COX-2 selective inhibitor drug, or substituting one for another on the grounds of mortality risk alone. • The Australian Department of Veterans' Affairs data sets make it possible to conduct timely record linkage studies of all-cause mortality from use of medicines in a large and clinically relevant population.

Aim: To determine hazard ratios for all-cause mortality in elderly Australian veterans taking COX-2 selective and non-selective NSAIDs.

Methods: Patient cohorts were constructed from claims databases (1997 to 2007) for veterans and dependants with full treatment entitlement irrespective of military service. Patients were grouped by initial exposure: celecoxib, rofecoxib, meloxicam, diclofenac, non-selective NSAID. A reference group was constructed of patients receiving glaucoma/hypothyroid medications and none of the study medications. Univariate and multivariate analyses were performed using Cox proportional hazards regression models. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated for each exposure group against each of the reference group. The final model was adjusted for age, gender and co-prescription as a surrogate for cardiovascular risk. Patients were censored if the gap in supply of study prescription exceeded 30 days or if another study medication was initiated. The outcome measure in all analyses was death.

Results: Hazard ratios and 95% CIs, adjusted for age, gender and cardiovascular risk, for each group relative to the reference group were: celecoxib 1.39 (1.25, 1.55), diclofenac 1.44 (1.28, 1.62), meloxicam 1.49 (1.25, 1.78), rofecoxib 1.58 (1.39, 1.79), non-selective NSAIDs 1.76 (1.59, 1.94).

Conclusions: In this large cohort of Australian veterans exposed to COX-2 selective and non-selective NSAIDs, there was a significant increased mortality risk for those exposed to either COX-2-selective or non-selective NSAIDs relative to those exposed to unrelated (glaucoma/hypothyroid) medications.