Vioxx Increases Risk for Several Conditions, Studies Find
The COX-2 inhibitor Vioxx, manufactured by Merck, increases risk for a number of conditions and increases risk for cardiovascular events in the early part of treatment, according to studies published on Tuesday on the Web site of the Journal of the American Medical Association, the Wall Street Journal reports (Loftus, Wall Street Journal, 9/13). Merck withdrew Vioxx from the market in September 2004 over safety concerns and faces more than 16,000 lawsuits related to the medication (California Healthline, 8/3).
For one study, researchers at Harvard Medical School and the Harvard School of Public Health analyzed the results of 114 clinical trials that involved 116,094 patients. The study finds that participants who took Vioxx had increased risk for arrhythmia and kidney disease (Wall Street Journal, 9/13).
Participants who took the COX-2 inhibitor Celebrex, manufactured by Pfizer, did not have similar increased risk for arrhythmia and kidney disease, the study finds (Fay Cortez/Zimm, Bloomberg/Philadelphia Inquirer, 9/13). In addition, the study finds that participants who took Vioxx had increased risk for hypertension and edema (Berenson, New York Times, 9/13).
The increased risk for arrhythmia found among participants who took Vioxx is significant because Merck last year in the first trial related to the medication argued that the treatment does not increase risk for the condition, according to the Journal (Wall Street Journal, 9/13).
Eric Ding, a co-author of the study, said that the link between Vioxx and increased risk for arrhythmia was known in 2004 and that the link between the medication and increased risk for kidney disease was known as early as 2000 (Ricks, Long Island Newsday, 9/13).
A second study, also an analysis of previous clinical trials, finds that Vioxx increased risk for cardiovascular events during the first 30 days of treatment. Merck has argued that Vioxx does not increase risk for cardiovascular events in the short term (Wall Street Journal, 9/13).
The study, conducted by researchers at the University of New South Wales in Australia, also finds that participants who took Vioxx had a higher risk for cardiovascular events than those who took Celebrex. Participants who took naproxen had a lower risk for cardiovascular events than those who took Vioxx or Celebrex, the study finds (New York Times, 9/13).
Both studies find that diclofenac, a pain medication that reached the market in 1998, "carries as high a risk of heart attack or stroke as Vioxx," the AP/New York Times reports.
The Australian study recommends that regulators consider whether diclofenac, marketed by Novartis under the brand names Voltaren and Cataflam, should remain on the market (AP/New York Times, 9/12).
In an editorial that accompanied the studies, FDA safety official David Graham criticizes how Merck conducted clinical trials of Vioxx and Arcoxia, a COX-2 inhibitor currently under review by FDA.
Graham in an interview said, "Merck practiced a campaign of misinformation by presenting data that violated rules of science, they weren't called to account by the journals that published their articles, and you have an FDA that hasn't been held to account. There is a lot of blame to go around" (Bloomberg/Philadelphia Inquirer, 9/13).
In the editorial, Graham writes that, with the application to market Arcoxia, "FDA, academia and the medical research enterprise are once again faced with the opportunity to forsake common sense by willfully accepting misdirection and disinformation presented in the guise of science."
According to a note in JAMA, FDA allowed Graham to write the editorial as a private citizen, rather than as an agency employee (Rubin, USA Today, 9/13).
Merck in a statement said, "Merck believes that observations published in today's Journal of the American Medical Association, and the opinions expressed in an accompanying editorial regarding a potential increased short-term cardiovascular thrombotic risk of Vioxx are not supported by the current weight of the clinical trial data" (Bloomberg/Philadelphia Inquirer, 9/13). Merck also said that the Harvard study "addressed the known renovascular risk associated" with Vioxx and added that the label of the medication includes information about increased risk for hypertension and edema in certain patients.
Novartis spokesperson John Gilardi said, "Other epidemiological data does not indicate an increased cardiovascular risk of diclofenac" (Wall Street Journal, 9/13).