A new study identified kidney-related risks for Merck & Co.'s (MRK) withdrawn Vioxx painkiller, while another study said the drug's cardiovascular risks began soon after treatment and not until long-term use, as the company has claimed.
One of these studies also found increased cardiovascular risks for an older painkiller, diclofenac, and suggests the drug's regulatory status should be reviewed. Diclofenac is marketed by Swiss drug company Novartis AG (NVS) under the brands Cataflam and Voltaren. This finding also raises questions about the design of a Merck study of a newer painkiller, Arcoxia, because it was compared with diclofenac.
Both studies were analyses of previous clinical trials, and were published online Tuesday by the Journal of American Medical Association. They were published a few weeks ahead of schedule due to what JAMA called "the public health implications of the findings."
Merck, based in Whitehouse Station, N.J., is in the midst of defending itself against thousands of lawsuits claiming that Vioxx use caused heart attacks and other injuries. Merck withdrew Vioxx from the market in September 2004 after a study showed it elevated the risk of cardiovascular events in people taking it for at least 18 months.
One government-funded study, conducted by researchers at Harvard Medical School and Harvard's public-health school, sought to analyze the kidney-related risks of several drugs including Vioxx and Pfizer Inc.'s (PFE) Celebrex. Vioxx and Celebrex are so-called Cox-2 inhibitors and were designed to provide pain relief without some of the gastrointestinal side effects of older painkillers.
The Harvard researchers analyzed the results of 114 clinical trials of the various drugs to identify such kidney-related problems as peripheral edema, which involves fluid buildup, and renal dysfunction and hypertension. They also sought to identify cases of arrhythmia, or irregular heartbeat, which sometimes occurs after kidney problems. Some 116,094 people participated in the trials.
The Harvard researchers concluded that Vioxx was associated with increased kidney and arrhythmia risks. But other Cox-2 inhibitors, including Celebrex, weren't associated with a statistically significant increased risk, so the researchers concluded there was no "class effect."
"Vioxx seems to increase renal and arrhythmia (risks) more than any of the other drugs," Eric Ding, one of the Harvard researchers, said in an interview.
The study also concluded that Vioxx's kidney-related risks could have been identified as early as 2000, and the arrhythmia risk could have been identified by the end of 2004. The authors suggested post-marketing surveillance of drugs should be improved in order to detect risks sooner.
The finding of an arrhythmia risk was significant because the first Vioxx trial last year, which Merck lost, involved a man who took Vioxx and died of arrhythmia. Merck had argued during the trial Vioxx wasn't linked to arrhythmias.
Another JAMA analysis was conducted by researchers at the University of Newcastle in Australia. It sought to compare the cardiovascular risks of Cox-2 inhibitors and such older painkillers as diclofenac. The researchers, who received funding from the National Health & Medical Research Council of Australia, analyzed previous clinical trials of the drugs.
The second study confirmed the elevated cardiovascular risks associated with Vioxx, and said the risks could be observed during the first 30 days of treatment. The authors said that finding was consistent with a recent re-analysis of a study that was halted in 2004 and prompted Merck to withdraw Vioxx. Merck has argued that study showed an increase in risk only after 18 months of use, but a recent re-analysis published in the New England Journal of Medicine contradicts Merck's claim.
Also, the JAMA analysis conducted by the Australian researchers found an elevated risk of cardiovascular events associated with diclofenac. "We believe there are grounds for reviewing its regulatory status," the authors wrote.
A Novartis spokeswoman couldn't immediately be reached.
The finding of a higher heart risk for diclofenac has implications for Merck too. Last month, Merck said preliminary data from a study of its painkiller Arcoxia showed its heart risks were no different from diclofenac. Arcoxia is approved in some countries but hasn't yet received U.S. Food & Drug Administration approval. Merck indicated last month it would continue seeking FDA approval.
But experts have criticized Merck's choice of diclofenac as a comparator, and the new JAMA analysis would seem to bolster the criticism.
In an accompanying JAMA editorial, a Food and Drug Administration drug-safety reviewer, David Graham, said Merck should have chosen other drugs for the Arcoxia study, such as naproxen. He said if naproxen had been used, it's highly likely that Arcoxia would have shown similar cardiovascular risks to Vioxx. Graham has been a vocal Merck critic, and he has been subpoenaed by Vioxx plaintiff attorneys to provide testimony. His editorial wasn't written on behalf of the FDA.
In a written statement, Merck defended its study of Arcoxia, noting it's the most widely used non-steroidal anti-inflammatory drug in the world. Merck didn't immediately address the findings about the kidney and arrhythmia risks of Vioxx in the other study.
No comments:
Post a Comment