Traditional nonsteroidal anti-inflammatory drugs and postmenopausal hormone therapy: a drug-drug interaction?
<h4>Background</h4>Suppression of prostacyclin (PGI2) is implicated in the cardiovascular hazard from inhibitors of cyclooxygenase (COX)-2. Furthermore, estrogen confers atheroprotection via COX-2-dependent PGI2 in mice, raising the possibility that COX inhibitors may undermine the cardi...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2007-05-01
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| Series: | PLoS Medicine |
| Online Access: | https://doi.org/10.1371/journal.pmed.0040157 |
| _version_ | 1818582272149815296 |
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| author | Luis Alberto García Rodríguez Karine Egan Garret A FitzGerald |
| author_facet | Luis Alberto García Rodríguez Karine Egan Garret A FitzGerald |
| author_sort | Luis Alberto García Rodríguez |
| collection | DOAJ |
| description | <h4>Background</h4>Suppression of prostacyclin (PGI2) is implicated in the cardiovascular hazard from inhibitors of cyclooxygenase (COX)-2. Furthermore, estrogen confers atheroprotection via COX-2-dependent PGI2 in mice, raising the possibility that COX inhibitors may undermine the cardioprotection, suggested by observational studies, of endogenous or exogenous estrogens.<h4>Methods and findings</h4>To identify an interaction between hormone therapy (HT) and COX inhibition, we measured a priori the association between concomitant nonsteroidal anti-inflammatory drugs (NSAIDs), excluding aspirin, in peri- and postmenopausal women on HT and the incidence of myocardial infarction (MI) in a population-based epidemiological study. The odds ratio (OR) of MI in 1,673 individuals and 7,005 controls was increased from 0.66 (95% confidence interval [CI] 0.50-0.88) when taking HT in the absence of traditional (t)NSAIDs to 1.50 (95% CI 0.85-2.64) when taking the combination of HT and tNSAIDs, resulting in a significant (p < 0.002) interaction. The OR when taking aspirin at doses of 150 mg/d or more was 1.41 (95% CI 0.47-4.22). However, a similar interaction was not observed with other commonly used drugs, including lower doses of aspirin, which target preferentially COX-1.<h4>Conclusions</h4>Whether estrogens confer cardioprotection remains controversial. Such a benefit was observed only in perimenopausal women in the only large randomized trial designed to address this issue. Should such a benefit exist, these results raise the possibility that COX inhibitors may undermine the cardioprotective effects of HT. |
| first_indexed | 2024-12-16T07:46:45Z |
| format | Article |
| id | doaj.art-e2744e61fc8c4edd98d74d44fa150e40 |
| institution | Directory Open Access Journal |
| issn | 1549-1277 1549-1676 |
| language | English |
| last_indexed | 2024-12-16T07:46:45Z |
| publishDate | 2007-05-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Medicine |
| spelling | doaj.art-e2744e61fc8c4edd98d74d44fa150e402022-12-21T22:38:56ZengPublic Library of Science (PLoS)PLoS Medicine1549-12771549-16762007-05-0145e15710.1371/journal.pmed.0040157Traditional nonsteroidal anti-inflammatory drugs and postmenopausal hormone therapy: a drug-drug interaction?Luis Alberto García RodríguezKarine EganGarret A FitzGerald<h4>Background</h4>Suppression of prostacyclin (PGI2) is implicated in the cardiovascular hazard from inhibitors of cyclooxygenase (COX)-2. Furthermore, estrogen confers atheroprotection via COX-2-dependent PGI2 in mice, raising the possibility that COX inhibitors may undermine the cardioprotection, suggested by observational studies, of endogenous or exogenous estrogens.<h4>Methods and findings</h4>To identify an interaction between hormone therapy (HT) and COX inhibition, we measured a priori the association between concomitant nonsteroidal anti-inflammatory drugs (NSAIDs), excluding aspirin, in peri- and postmenopausal women on HT and the incidence of myocardial infarction (MI) in a population-based epidemiological study. The odds ratio (OR) of MI in 1,673 individuals and 7,005 controls was increased from 0.66 (95% confidence interval [CI] 0.50-0.88) when taking HT in the absence of traditional (t)NSAIDs to 1.50 (95% CI 0.85-2.64) when taking the combination of HT and tNSAIDs, resulting in a significant (p < 0.002) interaction. The OR when taking aspirin at doses of 150 mg/d or more was 1.41 (95% CI 0.47-4.22). However, a similar interaction was not observed with other commonly used drugs, including lower doses of aspirin, which target preferentially COX-1.<h4>Conclusions</h4>Whether estrogens confer cardioprotection remains controversial. Such a benefit was observed only in perimenopausal women in the only large randomized trial designed to address this issue. Should such a benefit exist, these results raise the possibility that COX inhibitors may undermine the cardioprotective effects of HT.https://doi.org/10.1371/journal.pmed.0040157 |
| spellingShingle | Luis Alberto García Rodríguez Karine Egan Garret A FitzGerald Traditional nonsteroidal anti-inflammatory drugs and postmenopausal hormone therapy: a drug-drug interaction? PLoS Medicine |
| title | Traditional nonsteroidal anti-inflammatory drugs and postmenopausal hormone therapy: a drug-drug interaction? |
| title_full | Traditional nonsteroidal anti-inflammatory drugs and postmenopausal hormone therapy: a drug-drug interaction? |
| title_fullStr | Traditional nonsteroidal anti-inflammatory drugs and postmenopausal hormone therapy: a drug-drug interaction? |
| title_full_unstemmed | Traditional nonsteroidal anti-inflammatory drugs and postmenopausal hormone therapy: a drug-drug interaction? |
| title_short | Traditional nonsteroidal anti-inflammatory drugs and postmenopausal hormone therapy: a drug-drug interaction? |
| title_sort | traditional nonsteroidal anti inflammatory drugs and postmenopausal hormone therapy a drug drug interaction |
| url | https://doi.org/10.1371/journal.pmed.0040157 |
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