Study: Low-Dose Celebrex Poses No Heart Risk
But FDA Scientist Says Older Painkillers Can Raise Risk of Heart Attacks
Feb. 17, 2005 -- A previously undisclosed study presented by an FDA safety officer shows that the most common dose of the arthritis drug Celebrex does not increase heart attack risk.
However, higher doses of Celebrex - more than 200 mg a day - do raise the risk of heart attacks, other research shows.
The results, presented before an FDA advisory committee Thursday morning by agency whistleblower David Graham, MD, also suggest that the arthritis drug Vioxx can increase heart attack risk almost as soon as patients begin taking it. This contradicts findings that led to the removal of Vioxx from the market in September 2004.
Vioxx maker Merck says in a statement that their research showed an increased risk for heart attacks and strokes beginning after 18 months of continuous treatment with Vioxx, compared with a placebo.
Celebrex and Vioxx belong to the group of drugs called Cox-2 inhibitors. An expert panel is meeting this week to advise regulators on what to do about evidence that Cox-2 inhibitors and related medications increase the risk of heart attack and stroke. The agency is considering whether to restrict the use of the drugs, require more studies on their safety, or pull some of them from the market.
Maker of Celebrex Reacts
Graham became well known last fall when he testified to lawmakers that FDA officials had suppressed his attempts to warn the public about safety concerns with Vioxx before the drug was pulled from the market.
Preliminary new data from a study Graham conducted among California Medicaid patients showed that patients taking more than 200 mg of Celebrex per day had a 20% higher risk of heart attacks than those not taking the drug. Patients taking 200 mg a day or less showed no increased risk. A second unpublished study found similar results.
"Above 200 mg, we believe there is evidence of increased risk," Graham said.
The results go against at least five other studies, which found no increased risk of heart attacks with Celebrex. Graham said the two latest studies were the only ones to show the effects of higher doses, which are taken by millions of patients. One major National Institutes of Health study was halted several months ago after researchers noticed a
with 400 to 800 mg of Celebrex a day.
Officials from Pfizer, which markets Celebrex, told the panel Wednesday that most studies do not show an increased heart risk with their drug and that safety concerns appear unique to Vioxx.
The results have left experts to figure out whether heart problems are unique to Vioxx or whether they apply to the other drugs in the Cox-2 family. Graham said his conclusions suggest that the whole class, which includes Bextra and two other drugs not available in the U.S., have increased risk.
"I believe based on the evidence that there is a Cox-2 effect and that the Cox-2 effect is dose-dependent," he said.
Several committee members expressed doubt about Graham's conclusions, noting that there were problems with his studies, including the possibility that other factors may have increased heart risk.