The largest prospective trial ever examining the anti-inflammatory drug Vioxx as a chemoprevention agent found that the risk of developing a cardiovascular "event" - heart attacks and/or strokes - was almost double in patients who received the drug, compared to patients who took the placebo, according to a study out Feb. 15 on-line in The New England Journal of Medicine.
The risk was first discovered and reported last September by the study's safety monitoring board and led to the shutdown of the colon cancer chemoprevention trial and subsequent withdrawal of the drug from the U.S. market.
The trial, known as APPROVe (Adenomatous Polyp Prevention on Vioxx), was the longest test yet of Vioxx as a chemoprevention agent, and was designed to determine whether the drug could prevent the re-growth of precancerous colon polyps in people who had already had polyps removed. The prospective chemoprevention study randomized 2,586 participants from 108 centers in 29 countries to receive either 25 mgs. of Vioxx daily or a placebo drug for three years, 2001-2004. The trial was stopped September 30, 2004 - approximately two months before its planned completion.
According to Robert S. Bresalier, M.D., of The University of Texas M. D. Anderson Cancer Center and lead author of The New England Journal of Medicine study, 46 of the 1287 patients randomized to take Vioxx daily had confirmed cardiovascular events over a three year period - mostly heart attacks or strokes. In the 1,299 patients given a placebo drug, there were 26 events. Each group, however, had the same number of deaths and not all were related to heart attacks or strokes.
"The overall number of cardiovascular events is small, but, nevertheless, the difference between the groups is significant," says Bresalier, who is professor and chair of the Department of Gastrointestinal Medicine and Nutrition at M. D. Anderson and a member of the study's steering committee.
This study examined data on the 2,586 patients enrolled in the trial, all of whom had a history of adenomatous colon polyps. The most notable trend, according to Bresalier, was that patients did not begin to experience cardiovascular problems such as heart attacks or strokes until after 18 months of treatment. "In the first 18 months, the risks for the two treatments were similar," Bresalier says.