Vioxx risks confirmed by new studies
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The use of Vioxx (rofecoxib), the anti-inflammatory drug at the center of many high-profile lawsuits, does, in fact, increase the risk of heart attacks and strokes and may also adversely affect kidney function, according to the results of two studies released early by the Journal of the American Medical Association.
Both reports suggest that only Vioxx, not other COX-2 inhibitors, markedly raises the risk of these events.
Dr. Jingjing Zhang, from Harvard Medical School in Boston, and colleagues conducted an analysis of data from clinical trials to compare the kidney and heart rhythm risks associated with COX-2 inhibitors, including Vioxx, Celebrex (celecoxib), and others. A search of medical databases yielded 114 relevant trials with 116,094 participants.
A total of 6,394 adverse kidney events and 286 heart rhythm disturbances occurred in the study group. Statistical analysis suggested no evidence that all COX-2 inhibitors produced these side effects.
Compared with inactive “placebo” drug, Vioxx was associated with a nearly threefold increased risk of heart rhythm disturbances, or “arrhythmias.” In addition, use of the drug was tied to elevated risks of kidney problems.
By contrast, Celebrex use appeared to cut the risk of kidney dysfunction and high blood pressure by 39 and 17 percent, respectively, compared with the placebo. The other COX-2 inhibitors had no significant effect on the risk of arrhythmias or kidney problems, the authors note.
In the second report, Dr. Patricia McGettigan and Dr. David Henry, from the University of Newcastle in New South Wales, Australia, conducted a review of observational studies to assess the cardiovascular risks associated with COX-2 inhibitors and with older non-steroidal anti-inflammatory drugs (NSAIDs), such as naproxen and ibuprofen. Their database search yielded 7,086 potential studies, of which 23 were deemed eligible for analysis.
At doses greater than 25 mg per day, Vioxx more than doubled the risk of heart attack and stroke. At lower doses, the drug was associated with a 33-percent increased risk. These risks were apparent within the first month of treatment.
By contrast, at commonly used doses, Celebrex did not raise the risk of heart attack or stroke, the investigators point out.
The older NSAIDs generally had little effect on cardiovascular risk, the exception being diclofenac, which was associated with a 40-percent increased risk. Contrary to some reports, naproxen use did not appear to reduce the risk of heart attack or stroke.
In a related editorial, Dr. David J. Graham, from the US Food and Drug Administration in Silver Spring, Maryland, comments that the two reports “provide clarity on a topic that has been dominated more by disinformation than reason.”
Graham mentions that Vioxx-maker Merck is now seeking US approval of etoricoxib, a COX-2 inhibitor already approved for use in Europe and elsewhere.
The concern is that the major study (MEDAL), which showed etoricoxib to be safe, compared the drug against diclofenac, an agent that has now been tied to heart attack and stroke in two review studies.
“From the perspective of patient safety and rational therapeutics, naproxen, not diclofenac, should have been the reference drug in MEDAL,” Graham notes. “Had that been so, it is highly likely that etoricoxib would have been shown to be no different that its first-cousin rofecoxib with respect to cardiovascular risks.”
SOURCE: Journal of the American Medical Association, October 4, 2006.
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