Conclusive data about cardiovascular toxicity of nonsteroidal anti-inflammatory drugs ( NSAIDs ) are sparse. It has been hypothesized that regular NSAID use is associated with increased risk for cardiovascular events in postmenopausal women, and that this association is stronger with greater Cox-2 when compared with Cox-1 inhibition.
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 [ Celebrex ] ), nonselective agents with greater inhibition of Cox-2 than Cox-1 ( eg, Naproxen [ Naprosyn ] ), and nonselective agents with greater inhibition of Cox-1 than Cox-2 ( eg, Ibuprofen [ Brufen ] ) 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; P less than 0.001 ).
Selective cox-2 inhibitors were associated with a modest increased hazard for cardiovascular events ( HR=1.13; P=0.004 and Celecoxib only: HR=1.13; P=0.031 ).
Among Aspirin ( Acetylsalicylic acid ) 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 greater inhibition of Cox-2 than Cox-1 ( HR=1.17; P less than 0.001 and Naproxen only: HR=1.22; P less than 0.001 ).
This harmful association remained among concomitant Aspirin users.
Researchers did not observe a risk elevation for agents with greater inhibition of Cox-1 than Cox-2 ( HR=1.01; P=0.884 and Ibuprofen only: HR=1.00; P=0.996 ).
In conclusion, regular use of selective cox-2 inhibitors and nonselective NSAIDs with greater inhibition of Cox-2 than Cox-1 showed a modestly increased hazard for cardiovascular events.
Nonselective agents with greater inhibition of Cox-1 than Cox-2 were not associated with increased cardiovascular risk. ( Xagena )
Bavry AA et al, Circ Cardiovasc Qual Outcomes 2014;7: 603-610