Vioxx Side Effects Were Apparent Years Before The Drug Was Pulled Off the Market, Study Says
November 12, 2004 -- The arthritis drug Vioxx (rofecoxib) should have been withdrawn at least four years prior to September 2004, when it was finally pulled off the shelves, a new study concludes. Published in the medical journal Lancet, the report is based on a review of randomized controlled trials, observational studies, and data from the federal Food and Drug Administration (FDA) (Lancet. 2004 Dec 4-10; 364(9450): 2021-9). Among 21,432 patients, those taking Vioxx had a much greater rate of heart attacks (myocardial infarctions) than those taking other painkillers or a placebo.
The risk of heart attacks was high even among patients who used Vioxx for only a few months, according to the report. This result is in contrast to the APPROVe study, in which patients with colon cancer took Vioxx or a placebo. In that study, heart attack risks increased mainly in those patients who took Vioxx for at least 18 months.
The authors also challenged the claim that a more traditional painkiller, naproxen, was heart protective. That argument had been used to explain why patients who used Vioxx had four times the chance of having heart attacks compared to those who took naproxen (the VIGOR study, N Engl J Med. 2000 Nov 23; 343(21): 1520-8).
FDA Internal Report Links Vioxx to Heart Attacks
Just days before publication of the Lancet report, the FDA had posted a detailed internal study about Vioxx side effects on its web site. Dr. David Graham, associate director in the FDA Office of Drug Safety, and other researchers had analyzed the records of over 1.39 million patients at Kaiser Permanente hospitals who used Vioxx or other painkillers. They found that Vioxx increased the risk of heart attack and sudden cardiac death, and also concluded that naproxen was not heart protective.
About 92,791,000 patients took Vioxx in the United States from 1999--2003. Based on this figure and heart risk data, the report made this startling estimate-- 27,785 heart attacks and sudden cardiac deaths were due to Vioxx use during that period.
Dr. Graham has accused the FDA of delaying the report's publication and toning down the hazards of Vioxx. "The review and clearance process had been turned into a battleground, full of contention and intimidation because our managers, the people who fill out our performance evaluations, had created a system where it was taking a great risk to stand firm in our scientific beliefs," he told the New York Times last week. Richard Horton, the editor of the Lancet, goes even further in his views, saying that the FDA and Vioxx's manufacturer, Merck "acted out of ruthless, short-sighted, and irresponsible self-interest."
In response to its critics, the FDA has announced that it will sponsor a study by the Institute of Medicine to review the nation's drug safety system (FDA Statement, November 5). The agency also promises to develop a formal program for hearing and incorporating differing expert opinions about drug hazards.
Vioxx 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. Drug companies developed COX-2 inhibitors because these medicines were thought to cause less stomach upset than traditional NSAIDs such as ibuprofen and naproxen.
Celebrex (celecoxib) and Bextra (valdecoxib) are two COX-2 inhibitors that remain on the market. Bextra was recently linked to an increased risk of heart problems in patients who have undergone heart bypass surgery (see Bextra May Cause Heart Problems).