Pfizer: Celebrex Increases Risk of Heart Problems
On December 17, 2004, the drug giant Pfizer revealed that patients taking Celebrex in a long-term cancer-prevention trial had more than twice the number of fatal or non-fatal heart attacks compared with those taking a placebo. Another trial showed no increased risk. Dr. Marie Griffin, an epidemiologist and drug safety expert at Vanderbilt University, said the new findings on Celebrex is worrisome evidence suggesting that all these COX-2 drugs have similar risks.
Withdrawl of Vioxx Reveals Long-Standing Concerns Over Celebrex, Bextra and Others
The heart-attack findings for Celebrex come only 10 weeks after Merck & Co. withdrew its blockbuster arthritis drug Vioxx globally after a colon cancer trial confirmed long-standing concerns the drug is associated with heart attack and stroke. The withdrawl of the drug cast a cloud over an entire class of widely used arthritis and pain drugs.
Studies done in 1999 when Celebrex and Vioxx were approved suggest the same mechanism that inhibits inflammation and makes drugs easier on the stomach than traditional painkillers also blocks a substance that prevents heart problems, according to Dr. Garret FitzGerald, the University of Pennsylvania cardiologist who led the studies, which were designed by him but funded by the drug companies.
"I've been concerned all along," he said. "I believe this is a class effect," not just a problem with Vioxx, he said. FitGerald and his colleagues published two studies in 1999 and another in 2001 suggesting that COX-2 inhibitors were sparing the stomach at the expense of the heart.
COX-2 Inhibitors: Vioxx, Celebrex, Bextra
Vioxx (rofecoxib) represents a new generation of arthritis drug known as COX-2 inhibitors. Celebrex (celecoxib) and Bextra (valdecoxib) are other COX-2 inhibitors. While all nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit COX-2 (an enzyme linked to pain and inflammation), Vioxx, Celebrex and Bextra are called COX-2 inhibitors because they don't also inhibit COX-1, thought to keep the stomach lining intact (may be kinder to the digestive tract than other NSAIDs, although the FDA has not given their makers permission to make that claim).
A 2001 report in the Journal of the American Medical Association (JAMA) linked blood clots, heart attacks and strokes to Vioxx. The risk of cardiovascular problems, including heart attack, stroke, sudden death and blood clots, is believed by researchers to be two-to-four times higher in people who used Vioxx (rofecoxib group of drugs) than in the traditional, arthritis pain treatment NSAIDs. This was concluded by a study that involved 8,000 patients and compared the COX-2 inhibitor rofecoxib (Vioxx) with the traditional NSAID naproxen.
Scientists Urge Congressional Review
The JAMA author more recently chastised the FDA for not requiring Merck, the manufacturer of Vioxx, to do studies investigating heart problems associated with the drug years ago, and for allowing the company to blitz consumers with TV ads touting the drug.
Vioxx was the largest prescription drug withdrawl in history, "but had the many warning signs along the way been heeded, such a debacle could have been prevented," the JAMA author , Dr. Eric Topol, recently wrote. "Neither Merck nor the FDA fulfilled its responsibilities to the public...I believe there should be a full Congressional review of this case."
Merck and FDA officials said the mechanism underlying the problem with Vioxx wasn't known.
But FitzGerald and colleagues published two studies in 1999 and another in 2001 suggesting that by selectively blocking one of the two substances called prostaglandins that lead to inflammation, these so-called COX-2 inhibitors spare the stomach at the expense of the heart.
FitzGerald also challenged Pfizer's contention that no science shows increased risk from Celebrex. The original report from one study involving Celebrex found no increased risk of heart problems, but it covered only six months of a year-long study, according to the cardiologist. A look at the full data "reveals signs of increased cardiovascular risk," he writes.
The JAMA authors reported that the COX-2 users in both the Celebrex and Vioxx trials had similar heart attack rates: 8 out of 1,000 and 7.4 out of 1,000 respectively. In heart disease prevention studies, the authors wrote, the annual heart attack rate of those on a placebo was only 5 per 1,000.