Study: No Long-Lasting Vioxx Heart Risk

Risk Goes Away When Vioxx Use Stops; Low-Dose Celebrex Seems Safe

Medically Reviewed by Michael W. Smith, MD on January 31, 2005
From the WebMD Archives

Jan. 31, 2005 -- The heart attack risk linked to Vioxx goes away after a person stops taking the drug, data from elderly Canadians shows.

"It wasn't enough you took Vioxx three months ago -- you actually had to be currently exposed to have an increased risk of heart attack," James M. Brophy, MD, PhD, tells WebMD. "How long after you take Vioxx would you be considered at risk? More studies are needed to tease that out."

Brophy and colleagues at McGill University in Montreal reviewed medical records on nearly 114,000 people over the age of 66. They used the data to look at who did and who did not have a heart attack after beginning NSAID treatment.

NSAIDs (nonsteroidal anti-inflammatory drug) include traditional anti-inflammatory drugs, such as ibuprofen and naproxen, as well as newer ones, such as Celebrex and Vioxx. The new drugs -- known as Cox-2 inhibitors -- got their name because they selectively block an enzyme called Cox-2.

Brophy's team has more good news. Celebrex -- at low doses -- does not appear to increase heart attack risk.

"Yes, our study suggests that low-dose Celebrex is safe," Brophy says. "This is not a randomized study, so it is not proof of safety. But within the limits of an observational study, our data provides an element of confidence that Celebrex -- at least in conventional low dose of 200 milligrams per day -- appears to be very safe."

On the other hand, the study confirms that Vioxx -- even at a low dose -- actually does increase a person's risk of heart attack.

"Our data would tend to support the wisdom of taking Vioxx off the market," Brophy says. "The data already was rather conclusive from clinical trials. We add an element of precision, in that we have looked at a much larger population. ... In our study, 239 patients were taking Vioxx at the time of their heart attack. So we add a sense of confirmation and precision to this."

The findings come from elderly people who'd never had a heart attack before taking an NSAID.

How Safe Is High-Dose Celebrex?

Merck pulled Vioxx off pharmacy shelves when it became clear that the drug raised the risk of heart attacks. Fearing that other Cox-2 drugs might have similar -- if less dramatic -- side effects, doctors have been much more careful in prescribing Celebrex and Bextra. Some groups have called for a ban on these drugs until their heart safety can be assured.

Now, in an early release from the April 5, 2005 issue of Annals of Internal Medicine, Brophy's team provides more information. They found that:

  • Celebrex did not increase heart attack risk.
  • Vioxx did indeed increase heart attack risk.
  • Taking low-dose Vioxx -- 25 milligrams per day or less -- raised heart attack risk by 24%.
  • Taking high-dose Vioxx -- more than 25 milligrams per day -- increased heart attack risk by 73%.
  • People who took Vioxx in the past, but who stopped taking the drug, did not have a higher risk of heart attack.
  • Taking aspirin along with low-dose Vioxx protected against increased risk of heart attack, but taking aspirin along with high-dose Vioxx offered no protection at all.
  • Traditional NSAIDs did not increase heart attack risk. A report in December 2004 linked Aleve (naproxen) to an increase in heart attacks and strokes, but this study found no connection.

A close look at the findings does not give Celebrex a totally clean bill of health, says rheumatologist Axel Finckh, MD, a researcher at Brigham and Women's Hospital in Boston, who has studied Cox-2 inhibitors.

Finckh suggests that the findings provide added evidence that it is Cox-2 inhibition -- and not some other effect -- that underlies Vioxx's heart toxicity. Celebrex, too, is a Cox-2 inhibitor, although it is not nearly as potent as Vioxx in this regard.

"Very few of the Canadian patients took more than 200 milligrams per day of Celebrex -- and in clinical trials, the only heart risk was seen in those taking 400-800 milligrams per day," Finckh notes. "From this study we can see that lower doses of Celebrex seem to be relatively safe. I don't think we can say anything about higher doses of Celebrex."

And while Brophy's study shows that aspirin can remedy the heart toxicity of Cox-2 inhibitors, Finckh says this makes little clinical sense. Patients who do not suffer stomach and intestinal side effects from aspirin might as well take the equally effective and less-costly traditional NSAIDs.

"It abolishes the gastrointestinal security of the Cox-2 drugs to take aspirin," Finckh says. "If you need aspirin for heart protection, you might as well take a traditional NSAID for pain relief."

Show Sources

SOURCES: Lévesque, L.E. Annals of Internal Medicine, April 5, 2005; vol 142: published online Feb. 1, 2005. James M. Brophy, MD, PhD, associate professor, McGill University, Montreal. Axel Finckh, MD, Brigham and Women's Hospital, Boston.

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