Merck Knew About Vioxx Risks Early On, News Report Suggests
WHITEHOUSE STATION, NJ -- November 5, 2004 -- Merck, the manufacturer of the popular arthritis medicine, Vioxx, knew that the drug caused heart problems long before it was pulled from the market in September, a new report by the Wall Street Journal suggests. Vioxx increases the risk of stroke, heart attacks, and blood clots, according to a recent Merck-sponsored clinical trial known as APPROVe.
The APPROVe study found that colon cancer patients who took Vioxx had a much greater chance of developing serious heart conditions compared with those taking a sugar pill or placebo. Merck ended the study before its completion and stopped marketing Vioxx, claiming that the results were "unexpected." However, internal company documents and e-mail show that Merck had been covering up Vioxx's harmful effects, according to the Wall Street Journal.
In November, 1996, two and 1/2 years before Vioxx was approved, an internal company memo discussed a clinical trial to prove that Vioxx was gentler on the stomach than traditional painkillers. The memo said that aspirin should not be used in the trials, however, because there was a "substantial chance that significantly higher rates" of heart problems would be seen in the Vioxx group compared with those taking aspirin (Wall Street Journal, November 1, 2004). Two e-mails written in 1996 and 1997 also discussed Vioxx heart safety issues, the newspaper said.
In 1999, Merck began the Vioxx Gastrointestinal Outcomes Research (VIGOR) study. Eight thousand seventy-six rheumatoid arthritis patients were checked for stomach problems while taking painkillers (N Engl J Med. 2000 Nov 23; 343(21): 1520-8). Some took Vioxx, others were prescribed naproxen, an older and more traditional pain medicine. None of the patients had a history of heart disease. However, those taking Vioxx increased their chances of serious heart problems, including heart attacks, strokes, and blood clots.
In 2000, Merck's research chief, Dr. Edward Scolnick, stated in an e-mail that cardiovascular or heart problems due to Vioxx were "clearly there." He also admitted that Vioxx's side effects were "mechanism-based" and a problem that went beyond Vioxx's failure to have a heart protective benefit that might be present in other painkillers, the Wall Street Journal reported. Merck continued to market Vioxx and to deny the heart risks. A company training manual put it this way--"dodge" tough questions about Vioxx. Even more telling is a Merck press release dated April 20, 2000, which claimed to "confirm the favorable cardiovascular safety profile of Vioxx." The newspaper report also suggests that Merck attempted to influence doctors and to intimidate researchers so they would not report Vioxx hazards.
In February, 2001, the federal Food and Drug Administration (FDA) evaluated Vioxx data from VIGOR and other studies. They found the risk of stroke in patients taking Vioxx to be much greater than that of those who took the traditional painkiller naproxen. Later that year, the FDA sent a warning letter to Merck about its marketing to doctors. which it called "false, lacking in fair balance" and "misleading" (FDA Warning Letter to Merck, September 20, 2001). The letter concluded that Merck's ads "discounted the fact that in the VIGOR study, patients on Vioxx were observed to have a four to five fold increase in myocardial infarctions [heart attacks]" compared to patients on naproxen. The agency also objected to Merck's insistence that Vioxx did not increase the risk of heart attacks and that the VIGOR study was consistent with naproxen's ability to be heart protective.
The FDA began requiring Merck to include warnings about heart disease on its package inserts in April 2002. Even after the new package insert requirement and the FDA warning letter, Merck continued to use what many believe is deceptive advertising. Consider this excerpt from an ad in the November/December 2004 issue of AARP magazine, a publication widely read by seniors: "Vioxx cannot take the place of aspirin for the prevention of heart attack or stroke." What is missing from the main text of the ad is a statement that Vioxx may increase the risk of heart attack or stroke. Readers must go to the very fine print in the attached patient information to discover that heart problems have occurred in Vioxx users.
The Biology of Vioxx and COX-2 Inhibitors
Vioxx (rofecoxib) is a nonsteroidal anti-inflammatory drug (NSAID) that blocks cyclooxygenase, an enzyme needed for the production of prostaglandins. Prostaglandins may cause inflammation and pain. Vioxx interferes with the form of cyclooxygenase known as COX-2, and is therefore referred to as a COX-2 inhibitor. Before its recall, Vioxx was approved to reduce the pain of osteoarthritis, rheumatoid arthritis, and migraine headaches. It was also used to relieve short-term pain and the discomfort of severe menstrual cramps.
A drug manufacturer, Pfizer, markets two other COX-2 inhibitors, Celebrex (celecoxib) and Bextra (valdecoxib). Within weeks of the Vioxx recall, Pfizer reported that Bextra may cause heart problems in patients who have undergone heart bypass surgery (see Bextra May Cause Heart Problems). Some physicians now recommend the use of traditional NSAIDs such as ibuprofen instead of COX-2 inhibitors.