Do NSAIDs increase CVD risk in women?

A new analysis of data from participants in the Women’s Health Initiative (WHI) suggests that regular use of some nonsteroidal anti-inflammatory drugs (NSAIDs) may modestly increase cardiovascular risk in women. The findings were published in Circulation.

More than 160,000 postmenopausal women classified as regular users or nonusers of nonaspirin NSAIDs were represented in the study, led by investigators from the University of Florida. Cardiovascular disease (CVD) defined as cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke, was the primary outcome.

Using Cox regression, the investigators assessed NSAID use as a time-varying covariate and its association with CVD. They also performed a secondary analysis of the association between CVD and use of selective cox-2 inhibitors such as celecoxib, nonselective agents with cox-2>cox-1 inhibition such as naproxen, and nonselective cox-1>cox-2 inhibition such as ibuprofen.

Mean follow-up in the study was 11.2 years and 53,142 women reported using NSAIDs at some point during that period. The hazard for cardiovascular events was increased in women who used NSAIDs regularly compared with those who did not (hazard ratio [HR] 1.10; 95% confidence interval, 1.06-1.15; P<0.001). A modest increased hazard for cardiovascular events was seen in women who used selective cox-2 inhibitors (HR 1.13; 1.04-1.23; P=0.004 and celecoxib only: HR, 1.13; 1.01=1.27; P=0.031).

Concomitant selective cox-2 inhibitor use was not associated with increased hazard for cardiovascular events in aspirin users. The risk was increased for agents with cox-1>cox-1 inhibition (HR 1.17; 1.10-1.24; P<0.001 and naproxen only: HR 1.22; 1.12-1.34; P<0.001) and persisted with concomitant use of aspirin. In contrast, no increased risk was associated with agents with cox-1>cox-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).

Regular use of selective cox-2 inhibitors and nonselective NSAIDS with cox-2>cox-1 inhibition, the researchers concluded, may modestly increase the hazard for cardiovascular events in postmenopausal women. The same is not true, however, of nonselective agents with cox-1>cox-2 inhibition.

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