Abstract 10402: Association of Non-Steroidal Anti-Inflammatory Drugs With Adverse Cardiovascular Outcomes: Results From the Women’s Health Initiative
Introduction: Cardiovascular (CV) risks of non-steroidal anti-inflammatory drugs (NSAIDs) in women are unknown.
Hypothesis: Regular NSAID use is associated with increased risk of adverse CV events, which is mediated by greater cyclooxygenase (cox)-2 compared to cox-1 inhibition.
Methods: Post-hoc analysis of the observational and randomized clinical trial participants in the Women’s Health Initiative that enrolled postmenopausal women 50 to 79 years of age from 1993 to 1998. Participants provided a medication inventory at baseline and at years 1, 3, 6, and 9 (only updated at year 3 for observational study participants). NSAIDs were classified as cox-2 selective agents (e.g. celecoxib), agents with cox-2>cox-1 inhibition (e.g. naproxen), and agents with cox-1>cox-2 inhibition (e.g. ibuprofen). Cox regression examined NSAID use as a time varying covariate on the risk of the primary outcome: CV death, non-fatal myocardial infarction, or non-fatal stroke.
Results: Overall, 160,801 participants were available for analysis with a mean follow-up of 11.2 years. At baseline 31,433 participants reported regular NSAID use (naproxen=5625 participants, ibuprofen=17,108 participants; cox-2 selective agents were not represented at baseline, but were used later in follow-up). The primary outcome (n=12,733 events) occurred at a rate of 0.80 events per 100 person-years among regular NSAID users versus 0.69 events per 100 person-years among non-NSAID users, HR (95% CI)=1.11 (1.06-1.16), p<0.0001. Cox-2 selective agents were associated with increased risk: HR=1.14 (1.05-1.24), p=0.0023; celecoxib only HR=1.14 (1.02-1.27), p=0.026. The association was similar among agents with cox-2>cox-1 inhibition: HR=1.18 (1.11-1.25), p<0.0001; naproxen only HR=1.23 (1.12-1.34), p<0.0001. There was no association among agents with cox-1>cox-2 inhibition: HR=1.01 (0.95-1.07), p=0.82; ibuprofen only HR=1.00 (0.94-1.07), p=0.93.
Conclusions: The use of cox-2 selective and non-selective agents with cox-2>cox-1 inhibition showed a modestly increased hazard for CV events. We did not identify greater CV risk for medications with more cox-1>cox-2 inhibition (e.g. ibuprofen); therefore, these agents may be safer for long-term use among postmenopausal women.
- © 2013 by American Heart Association, Inc.