MADRID, Spain—Nonsteroidal anti-inflammatory drugs (NSAIDs) may interact with hormone therapy (HT), potentially offsetting the cardioprotective effects that have been suggested by observational studies of either endogenous or exogenous estrogens, according to Spanish investigators. The study appears online in Public Library of Science (PLoS).1

"The results of this study raise the possibility that concomitant medication with NSAIDs may undermine a cardioprotective effect of HT in peri-and post-menopausal women." —Luis Alberto García Rodríguez, MD.
While "provocative rather than conclusive ... the results of this study raise the possibility that concomitant medication with NSAIDs may undermine a cardioprotective effect of HT in peri-and post-menopausal women," report researchers led by Luis Alberto García Rodríguez, MD, with the Centro Español de Investigación Farmacoepidemiológica, in Madrid, Spain. Their hypothesis is that coxibs may increase risk of heart attack by suppressing prostacyclin (PGI2), while estrogen may protect the heart via increasing production of PGI2.

Drug-drug interaction?

The study found that women who were currently taking HT had a lower risk of heart attack than women who did not take HT, but this reduction in risk seemed to disappear among women who were taking NSAIDs and hormones. In fact, women who were taking NSAIDs and HT had an increased risk of having a heart attack compared with women taking neither.


Using the United Kingdom's General Practice Research Database, the researchers identified 1673 women who had a heart attack or died from heart disease, and compared them with 7005 ‘control' women matched for age and use of HT and NSAIDs. There were 21 NSAIDs used by women of both groups, but diclofenac, ibuprofen, and naproxen were the most common; aspirin was excluded.

The odds ratio of myocardial infarction in 1673 in both groups increased from 0.66 (95% confidence interval [CI] 0.50-0.88) for HT users to 1.50 (95% CI 0.85-2.64) for users taking combination HT and NSAIDs, resulting in a significant (P <.002) interaction.

"Whether estrogens confer cardioprotection remains controversial," the researchers conclude. "Should such a benefit exist, these results raise the possibility that COX inhibitors may undermine the cardioprotective effects of HT."

Part of the controversy stems from the Women's Health Initiative study, which found that perimenopausal women taking HT actually had an increased risk of heart attack. Other studies have shown a cardioprotective effect of estrogen use in perimenopausal women.

CIAOMed spoke with a WHI chief investigator JoAnn E. Manson, MD, DrPH, chief of preventive medicine at Harvard's Brigham and Women's Hospital, and professor of medicine at Harvard Medical School, both in Boston. "These findings are intriguing and warrant further study; however, NSAID use did not explain the absence of heart protection in the WHI and we did look at that in detail." The WHI study showed a similar risk of heart disease among HT users irrespective of NSAID use.

"I don't think at the present time we can say that hormone therapy protects the heart in the absence of NSAID use. The totality of evidence does not support that statement. Both NSAIDs and HT should be avoided in women at high risk for cardiovascular disease and, in particular, combinations of these medications should be avoided in high-risk women," Dr. Manson advised.

Reference

1. García Rodríguez LA, Egan K, Fitzgerald GA. Traditional nonsteroidal anti-inflammatory drugs and postmenopausal hormone therapy: a drug-drug interaction? PloS. 2007;4:[Epub ahead of print].