Journal of Family Practice - Rofecoxib, diclofenac, and indomethacin increase risk of CVD
* Clinical Question
Which NSAIDs increase the risk of cardiovascular disease?
* Bottom Line
Rofecoxib (Vioxx), diclofenac (Voltaren, Cataflam), and indomethacin (Indocin) are associated with a significant increased risk of cardiovascular disease (CVD). It is likely that all nonsteroidal anti-inflammatory drugs (NSAIDs) carry some risk, but the risks may vary between medicines. Current evidence does not point to an increased risk for low-dose (over-the-counter) ibuprofen, and this remains safe to use at recommended doses. (LOE: 2a-)
Study Design
Systematic review
Funding
Foundation
Setting
Various (meta-analysis)
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Synopsis
Recent evidence that rofecoxib increases the risk of CVD has raised concern about other NSAIDs. These investigators searched multiple databases including Medline, EMBASE, the Cochrane Library, abstracts of scientific meetings, and bibliographies of relevant studies for reports on cardiovascular events and NSAID use.
Of 7086 potentially eligible titles, 17 case-control studies (including 86,193 cases) and 6 cohort studies (including 75,520 users) met study criteria. Most exclusions were a result of reports not providing sufficient information on study outcomes or the drugs of interest. The mean age of study participants was rarely less than 55 years, and in most cases was grater than 60 years.
Two individuals independently extracted data and assessed study quality with disagreements resolved by consensus. Individual studies underwent assessment using a standardized instrument. All studies scored well (7-8 points in total from a possible 9).
As expected, rofecoxib use significantly increased the risk of CVD, with risk being highest with doses in excess of 25 mg/d. Diclofenac and indomethacin were also associated with a significantly increased risk of CVD. Data on meloxicam (Mobic) came from 3 trials, only one of which showed a statistically significant elevated risk.
Authors of the article state that these data do not allow definite conclusions about the risk of meloxicam. Celecoxib (Celebrex), naproxen, piroxicam, and ibuprofen exposure did not increase CVD risk. Stay tuned, however, as more studies are forthcoming shortly. In a related study in the same journal (Zhang J, Ding E, Song Y, JAMA 2006; 296:1619-1632), only rofecoxib was associated with a significant increased risk of renal events and heart arrhythmia. Celecoxib was significantly associated with a reduced risk of renal dysfunction.
FAST TRACK
All NSAIDs likely carry some risk of CVD; evidence does not point to increased risk for over-the-counter ibuprofen
McGettigan P, Henry D. Cardiovascular risk and inhibition of cyclooxygenase. A systematic review of the observational studies of selective and nonselective inhibitors of cyclooxygenase 2. JAMA 2006; 296:1633-1644.
COPYRIGHT 2006 Dowden Health Media, Inc.
COPYRIGHT 2008 Gale, Cengage Learning
