Three Studies Indicate Link Between COX-2 Inhibitors, Increased Risk for Cardiovascular, Other Events
COX-2 inhibitors are "at risk of being removed from the market" because of their link to increased risk for cardiovascular and other events, according to a "sweeping series of studies" on the medications released on Wednesday by the New England Journal of Medicine, Long Island Newsday reports. NEJM released the three studies one month early in conjunction with FDA meetings this week on the safety of COX-2 inhibitors (Ricks, Long Island Newsday, 2/16).
Members of the FDA arthritis and drug safety and risk management advisory committees on Wednesday will begin meetings to determine whether to remove COX-2 inhibitors from the market over safety concerns. The members of the advisory committees will review hundreds of documents from FDA scientists and the manufacturers of COX-2 inhibitors and hear testimony from scientists, physicians and patients (California Healthline, 2/15).
Two of the studies released by NEJM -- which involved the COX-2 inhibitors Vioxx, which Merck in late September 2004 withdrew from the market over safety concerns, and Celebrex, manufactured by Pfizer -- examined whether the medications could help prevent new colorectal polyps in patients who previously received treatment for the growths.
According to Robert Bresalier, lead researcher for one the of the studies, the results indicated that Vioxx doubled risk for heart attack and stroke -- which prompted researchers to end the study early -- and increased risk for hypertension, pulmonary edema and congestive heart failure. Scott Solomon of Brigham and Women's Hospital, who led the second study -- in which participants received Celebrex -- said that the results indicated the medication also increased risk for cardiovascular events and that researchers will not reach conclusions about whether the treatment could help prevent colorectal polyps for at least three months.
The third study, conducted at the Texas Heart Institute, examined heart surgery patients who took the COX-2 inhibitor Bextra, also manufactured by Pfizer. The study found that 7.4% of the participants experienced heart attacks, kidney damage, ulcers or problems with wound healing.
In an editorial that accompanied the studies, NEJM editor Jeffrey Drazen wrote that FDA should "ask whether the use of the drugs can now be justified." Researchers Bruce Psaty and Curt Furberg wrote in a second editorial that based on the results of the studies, "physicians are dismayed, pharmaceutical companies are embarrassed and financially threatened, and patients are injured."
According to Bresalier, "We just have to sit back now and when the smoke clears try to assess the risk versus benefit with these agents for a whole spectrum of diseases." Psaty added, "I think we'll have to see what the totality of the evidence looks like at the FDA hearing -- whether they should remain on the market" (Long Island Newsday, 2/16).
The Vioxx, Celebrex and Bextra studies, as well as the editorials written by Drazen and Psaty and Furberg, are available online. Note: You must have Adobe Acrobat Reader to view the studies and editorials.
Philadelphia Inquirer: The Inquirer on Wednesday examined the recent pharmaceutical industry "slump -- rather, the hugely profitable industry's version of a slump" -- that has resulted from the Vioxx withdrawal and could prompt some companies to revise the "'blockbuster business model' that underpins Big Pharma." As a result of the Vioxx withdrawal and other prescription drug safety concerns, the pharmaceutical industry could face new FDA regulations, which has prompted some companies to reduce costs through layoffs and increase expenditures on research. Some Wall Street analysts predict a decrease in the growth rate of the pharmaceutical industry over the next few years, but whether the "glory days are gone for good, or just detoured, is unknown," the Inquirer reports (Ginsberg, Philadelphia Inquirer, 2/16).
- Wall Street Journal: The Journal on Wednesday examined the "challenges that regulators, drug companies and doctors alike face as they confront troubling evidence of potentially serious risks of medicines that have provided benefits to millions of patients." According to the Journal, "At the heart of the conundrum is how people perceive medical risk" and how "aggressive" marketing campaigns might affect patient perceptions of the risks and benefits of medications. Although the COX-2 inhibitor "controversy is fraught with conflicting and hard-to-interpret data," some physicians hope the FDA meetings this week will "provoke more conversations between doctors and patients that would blunt the impact of marketing campaigns and instead lead to a better match of benefit and risk," the Journal reports (Winslow, Wall Street Journal, 2/16).
- CBS' "Evening News": The program includes comments from Dr. David Graham, associate director of the FDA Office of Drug Safety (Attkisson, "Evening News," CBS, 2/15). The complete segment is available online in RealPlayer.
- CBS' "Evening News": The program includes comments from Dr. Joseph Markenson, a professor of clinical medicine at Weill Medical College at Cornell University and a physician at the Hospital for Special Surgery, and Wayne Ray, a professor of preventive medicine and director of the Division of Pharmacoepidemiology at Vanderbilt University (Kaledin, "Evening News," CBS, 2/15).
- NPR's "All Things Considered": The program includes comments from Daniel Solomon, an assistant professor and rheumatologist at Harvard Medical School and clinical practitioner at Brigham and Women's Hospital; Jerry Avorn, a professor at Harvard Medical School, Elizabeth Tindall, president of the American College of Rheumatology; and arthritis patients (Knox, "All Things Considered," NPR, 2/15). The complete segment is available online in RealPlayer.