New research suggests that top-selling pain reliever Celebrex does not carry the same heart attack risk as Vioxx, a similar drug pulled from the market in September because of safety concerns.
The study by researchers at the University of Pennsylvania is the first to compare the two arthritis drugs since the recall, and contradicts claims by other scientists that all so-called cox-2 inhibitors may carry similar dangers.
“Vioxx and Celebrex look different. Relative to Celebrex, Vioxx had about a threefold greater risk of heart attacks,” said Dr. Stephen Kimmel, associate professor of medicine and epidemiology and lead author of the study. “What that implies is that all cox-2 inhibitors may not be the same.”
The study, funded by the makers of both drugs and the federal government, was published in Tuesday’s Annals of Internal Medicine. Researchers surveyed 1,718 patients in the five-county Philadelphia area who had heart attacks and were treated at one of 36 hospitals, and a comparison group of 6,800 people in the region.
The chances of having a heart attack were 2.72 times greater in Vioxx users than in Celebrex users, the researchers said.
But the researchers also found that patients using either drug were not at a significantly greater risk of having a heart attack than those who did not use either drug. In fact, Celebrex users had a lower risk of a heart attack than people who didn’t take either drug, though the researchers said that finding could have happened by chance.
Link still remains unclear, doctors warn
In an accompanying editorial, two Boston doctors warned that the connection between heart disease and cox-2 inhibitors remains unclear. As a result, they recommended that doctors avoid prescribing any drug in that class to patients already in danger of heart disease, unless they run a significant risk of gastrointestinal problems. Cox-2 inhibitors are believed to be easier on the stomach than other pain relievers.
“We don’t think that we really understand what is triggering the increased risk of heart problems in some patients,” said Dr. Axel Finckh, rheumatology researcher at Brigham and Women’s Hospital. “We cannot exclude the possibility that there is a cox-2 class effect.”
Merck & Co. pulled Vioxx from the market Sept. 30 after a study indicated the popular pain reliever doubled the risk of heart attacks and stroke when taken for longer than 18 months.
In October, sales of the Pfizer Inc. drug Celebrex topped $260 million, or 63.5 percent of the market for cox-2 inhibitors, according to IMS Health data.
Officials at Pfizer had no immediate comment.
“Overall, observational studies on the risk of cardiovascular events with Vioxx have had inconsistent results, and this study only adds to that literature,” Merck spokesman Tony Plohoros said.
'Not a clean bill of health for Celebrex'
Dr. Garret FitzGerald, a Penn cardiologist and pharmacologist, questioned whether it proved anything new. He is among a number of doctors concerned that all cox-2 inhibitors, which block the enzyme that causes the pain and swelling of arthritis, may raise the risk of heart problems.
Studies done five years ago — when Celebrex and Vioxx were approved — suggest the same mechanism that inhibits inflammation and makes the drugs easier on the stomach also blocks a substance that prevents heart problems, FitzGerald said.
“It’s not a clean bill of health for Celebrex,” FitzGerald said of Kimmel’s study. “It’s well recognized that these types of studies are not conclusive.”
To find proof, he said, researchers would have to conduct a random study involving people who took Vioxx, people who took Celebrex and people who took a placebo — all before they had heart attacks. The authors of the latest study agreed that further research is needed.
Some doctors have been wary of prescribing Pfizer’s Bextra, another cox-2 drug, for fear it can cause the same type of heart problems as Vioxx. A preliminary study discussed at the American Heart Association’s annual meeting in November indicated Bextra more than doubled the risk of heart attack and stroke among heart disease patients taking the pain reliever.
The Food and Drug Administration has promised to convene a panel early next year to re-examine all cox-2 drugs.