The New York Times
August 25, 2004
NEW YORK (Reuters) – Patients taking Merck & Co. Inc.’s Vioxx arthritis drug had a 50 percent greater chance of heart attacks and sudden cardiac death than individuals using Pfizer Inc.’s rival Celebrex medicine, according to a large study financed by the U.S. Food and Drug Administration.
The study, presented at an epidemiologists conference in Bordeaux, France, on Wednesday, is the latest to suggest that the $2.5-billion-a-year drug increases the danger of heart attacks. Lingering safety concerns have badly hurt sales of Vioxx in recent years.
The study also found patients taking the highest recommended daily dosage of Vioxx had three times the risk of heart attack and sudden cardiac death as those not taking standard painkillers.
Sudden cardiac death, an electrical disturbance of the heart that is not considered a heart attack, is the biggest cause of death in the United States.
Researchers came up with the potentially damaging findings on Vioxx after analyzing the medical records of 1.4 million people insured by Kaiser Permanente, the Oakland, California-based health maintenance organization.
The study found 8,199 heart attacks and cases of sudden cardiac death among the Kaiser members between 1999 and 2001.
Dr. David Graham, lead investigator for the trial, said another major finding was that patients taking the typical starting dose of Vioxx had a 50 percent greater chance of heart attack and sudden cardiac death than patients taking any dose of Celebrex.
“Based upon the evidence in this study, I don’t think doctors should prescribe high-dosage Vioxx, and patients shouldn’t take it,” Graham said in an interview.
Asked if the FDA might consider banning use of high-dose Vioxx, given the findings, Graham said, “The FDA has to decide whether they think a three-fold increase in heart attacks outweighs the benefits of the drug.”
Alise Reicin, vice president of clinical research at Merck, said the study was merely “observational,” and not the preferred formal kind of study in which patients are enrolled and then randomly placed into different treatment groups.
“Observational studies have inherent limitations,” she said, and often produce inaccurate results.
Most patients take daily Vioxx doses of 12.5 milligrams and 25 milligrams for arthritis. But a higher dose of 50 milligrams is approved by the FDA for treatment of pain for no longer than five days.
“The problem is that some patients continue to take it for 30, 60, or 90 days,” Graham said, putting themselves at elevated risk of heart attack and sudden cardiac death.
Graham, senior scientist for the FDA’s Office of Drug Safety, said his own interpretations of the data did not necessarily reflect the views of the FDA.
In Merck’s own 8,000 patient trial of Vioxx before the drug was launched in 1999, over twice as many arthritis patients taking it had heart attacks and strokes than those who took naproxen — one of the most popular older arthritis treatments.
Merck has argued that Vioxx itself did not cause the heart attacks but that naproxen was somehow preventing them — putting Vioxx in an unfair bad light in the head-to-head trials.
But Graham said his trial suggested that naproxen actually slightly increases the risk of heart attacks, casting doubt on Merck’s theory.
Reicin said a group of smaller Merck trials have not shown any greater risk of heart attack for Vioxx than Celebrex.
Although Merck has steadfastly defended the safety of Vioxx, its sales have flattened in recent years amid the lingering safety concerns and cardiovascular risks cited by independent researchers.
That has allowed Celebrex and a sister Pfizer drug, called Bextra, to dominate the market for their class of arthritis drugs, called Cox-2 inhibitors.
The newer drugs are designed to fight inflammation and pain while reducing the risk of ulcers caused by traditional non-steroidal anti-inflammatory drugs (NSAIDs), such as aspirin, naproxen and ibuprofen.