Impact of NSAIDS on Mortality and the Effect of Preexisting Coronary Artery Disease in US Veterans

Background: Evidence indicates increased risk of cardiovascular events with certain nonsteroidal anti-inflammatory drug (NSAID) use; however, less is known about NSAID use and mortality. In addition, it is unclear whether risks observed with NSAIDs are modified by coronary artery disease (CAD). The association between NSAID exposure and mortality, cardiovascular, and cerebrovascular events was examined. Methods: A nested case-control study in a cohort of 565,451 US veterans with a diagnosis of osteoarthritis was conducted. The cohort was divided into those with preexisting CAD (16,869 cases) and those without (11,912 cases). Up to 20 controls were selected for each case. Results: The average age of participants was 69.8 years (non-CAD) and 71.8 years (CAD). Relative to no exposure, adjusted odds ratios for cardiovascular or cerebrovascular events for any NSAID were 1.14 (95% confidence interval [CI], 1.08-1.21) in the non-CAD group and 1.18 (95% CI, 1.11-1.27) in the CAD group. Exposure to NSAIDs was associated with a decreased risk of all-cause mortality in both the non-CAD (0.72, 95% CI, 0.68-0.77) and CAD (0.79, 95% CI, 0.73-0.86) groups. Conclusions: As in previous reports, there was an increased risk of cardiovascular and cerebrovascular events for NSAIDs. However, NSAID exposure was associated with a reduced risk of death. This study raises important questions about NSAIDs in patients with osteoarthritis given that they seem to increase the risk of cardiovascular events but decrease overall mortality.