RESEARCH · July 08, 2014
TAKE-HOME MESSAGE
- This study investigated the association of regular use of NSAIDs with increased risk for cardiovascular events in postmenopausal women. Using data from the Women’s Health Initiative, investigators identified 53,142 women as regular NSAID users. Overall, NSAID use was associated with an increased hazard for cardiovascular events compared with no NSAID use. More specifically, selective COX-2>COX-1 inhibitors and nonselective COX-2 agents were associated with increased hazard for cardiovascular events. However, nonselective agents with COX-1>COX-2 inhibition did not result in increased risk.
- Regular NSAID use is associated with increased cardiovascular risk in postmenopausal women and thus should be used with caution in this population.
ABSTRACT
BACKGROUND
Conclusive data about cardiovascular toxicity of nonsteroidal anti-inflammatory drugs (NSAIDs) are sparse. We hypothesized that regular NSAID use is associated with increased risk for cardiovascular events in postmenopausal women, and that this association is stronger with greater cyclooxygenase (cox)-2 when compared with cox-1 inhibition.
METHODS AND RESULTS
Postmenopausal women enrolled in the Women’s Health Initiative were classified as regular users or nonusers of nonaspirin NSAIDs. Cox regression examined NSAID use as a time-varying covariate and its association with the primary outcome of total cardiovascular disease defined as cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. Secondary analyses considered the association of selective cox-2 inhibitors (eg, celecoxib), nonselective agents with cox-2>cox-1 inhibition (eg, naproxen), and nonselective agents with cox-1>cox-2 inhibition (eg, ibuprofen) with the primary outcome. Overall, 160 801 participants were available for analysis (mean follow-up, 11.2 years). Regular NSAID use at some point in time was reported by 53 142 participants. Regular NSAID use was associated with an increased hazard for cardiovascular events versus no NSAID use (hazard ratio [HR], 1.10; 95% confidence interval, 1.06-1.15; P<0.001). Selective cox-2 inhibitors were associated with a modest increased hazard for cardiovascular events (hazard ratio, 1.13; 1.04-1.23; P=0.004 and celecoxib only: HR, 1.13; 1.01-1.27; P=0.031). Among aspirin users, concomitant selective cox-2 inhibitor use was no longer associated with increased hazard for cardiovascular events. There was an increased risk for agents with cox-2>cox-1 inhibition (HR, 1.17; 1.10-1.24; Pcox-2 inhibition (HR, 1.01; 0.95-1.07; P=0.884 and ibuprofen only: HR, 1.00; 0.93-1.07; P=0.996).
CONCLUSIONS
Regular use of selective cox-2 inhibitors and nonselective NSAIDs with cox-2>cox-1 inhibition showed a modestly increased hazard for cardiovascular events. Nonselective agents with cox-1>cox-2 inhibition were not associated with increased cardiovascular risk.
Circulation: Cardiovascular Quality and Outcomes
Nonsteroidal Anti-Inflammatory Drugs and Cardiovascular Outcomes in Women: Results From the Women’s Health Initiative
Circ Cardiovasc Qual Outcomes 2014 Jul 08;[EPub Ahead of Print], AA Bavry, F Thomas, M Allison, KC Johnson, BV Howard, M Hlatky, JE Manson, MC Limacher
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.