Arthritis Drug Linked to Heart Failure
Vioxx, but Not Celebrex, Found to Increase Heart Failure
By Salynn Boyles
WebMD Medical News
Reviewed By Michael Smith, MD
May 27, 2004 -- A new report from Canadian researchers shows an increased risk for heart failure among elderly people using the drug Vioxx. This comes after several previous studies have linked the widely used arthritis drug to increased heart attack risk.
Researchers examined hospital records for 39,000 elderly residents of Ontario, Canada after they were prescribed the arthritis drugs Vioxx or Celebrex or older nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen and naproxen. They were compared with another 100,000 elderly people who did not take any of the drugs.
Researchers did not see an increase in hospital admissions because of heart failure among patients who took Celebrex. However, compared with Celebrex users, those taking Vioxx were 80% more likely to be admitted to the hospital with heart failure. There was a slight increase for those taking older NSAIDs but the findings were not strong enough to tell for sure.
Vioxx and Celebrex belong to a class of drugs called Cox-2 inhibitors -- so called because they calm inflammation by blocking an enzyme called Cox-2. They were developed to help decrease the risk of side effects, such as stomach ulcers and bleeding, and kidney problems, sometimes seen with the older NSAIDs.
Researcher Muhammad Mamdani, PharmD, says the study shows important differences between the older NSAIDs and the two Cox-2 inhibitors with respect to heart failure risk.
But he explains that the message is not that one Cox-2 is safer for use by elderly patients, noting that increases in the number of patients requiring treatment for high blood pressure were seen among patients taking Vioxx and Celebrex as well as the older NSAIDs. However, more Vioxx patients required high blood pressure treatment than Celebrex patients. How Bextra, the newest Cox-2 inhibitor, fits into the picture is unknown as it was not included in Mamdani's study.
"There has been a rapid adoption of Cox-2 inhibitors into clinical practice, and I think that more judicious prescribing of these drugs is needed," Mamdani says.
Vioxx Maker Responds
A spokeswoman for Vioxx manufacturer Merck tells WebMD that the pharmaceutical company "is confident in [the drug's] overall safety and efficacy profile."
"As noted in the prescribing information for Vioxx, congestive heart failure is a rare event, having been reported in less than an estimated 0.1% of patients taking part in our osteoarthritis clinical studies," says Mary Elizabeth Blake.
Blake noted that the way the study was performed (researchers reviewed medical records rather than following patients while they took the drugs) limits the conclusions that can be drawn from it.
"It is not clear if these patients had preexisting heart conditions prior to entering the study, and important cardiovascular risk factors such as diet, weight, and alcohol consumption could not be controlled for."
American Heart Association spokesman Clyde Yancy, MD, agrees that the study "cannot be considered the definitive word on risk." Yancy is a professor of medicine at the University of Texas Southwest Medical School.
"It is really hard for me to believe that the differences between these two Cox-2s are so fundamental that you would have almost no risk in terms of heart failure with one drug and such a significant risk with the other," he says.
A study published in mid March found a doubling of heart attack risk among people taking Vioxx in conjunction with high blood pressure medication. And in 2001, researchers at The Cleveland Clinic reported that people taking either Vioxx or Celebrex for arthritis were twice as likely to have heart attacks as those taking the older NSAID naproxen. On the basis of that trial, the FDA required a label change for the COX-2s to include information about heart attack risk.
Yancy says studies are needed to clarify the risk, but he says that he still prescribes Cox-2s to some of his heart patients with arthritis.
"Like all decisions in medicine, this is one that must be personalized," he says. "For some patients, the benefits of being free of pain and being able to move around better probably outweigh the risks."
SOURCES: Mamdani, M. The Lancet, May 29, 2004; vol 363: pp 1751-1756. Muhammad Mamdani, PharmD, senior scientist, Institute for Clinical Evaluative Sciences, Toronto; and associate professor, University of Toronto. Mary Elizabeth Blake, spokeswoman, Merck. Clyde Yancy, MD, professor of medicine, University of Texas Southwest Medical Center at Dallas; and spokesman, American Heart Association.