Renewed Scrutiny for Vioxx, Other COX-2 Inhibitors
Feb. 16–Heart bypass patients and people at risk for colon cancer were at increased danger of heart attacks or strokes when treated with Vioxx, Celebrex and Bextra, according to three new studies published Tuesday, offering further evidence of problems posed by drugs known as COX-2 inhibitors.
The studies — two from Houston and one from Harvard — were released early by the New England Journal of Medicine for public health reasons and to coincide with a three-day Food and Drug Administration meeting.
At the meeting, which starts today, physicians and scientists will try to find a balance between benefits and risks of COX-2 drugs, which are taken by millions of people.
“I think we are at risk of losing the class of drugs,” said Dr. Robert Bresalier, a University of Texas M.D. Anderson Cancer Center researcher who led a study on the use of Vioxx in preventing cancer. “That’s why it’s important to put it in perspective of absolute risk.”
The U.S. Department of Health and Human Services announced Tuesday that the FDA will establish a new independent Drug Safety Oversight Board to monitor FDA-approved medicines once they’re on the market, and update physicians and patients with emerging information on risks and benefits.
Drug side effects often become evident after a drug reaches the market and is taken by millions of people. Initial studies designed to show safety and effectiveness of a drug to gain FDA approval may involve too few patients to uncover a relatively rare side effect.
Health officials have been scrutinizing COX-2 inhibitors — originally approved as painkillers for arthritis and acute pain in patients whose stomachs can’t tolerate Tylenol or aspirin — since last September. At that time, manufacturer Merck withdrew Vioxx from stores after studies revealed that it nearly tripled heart attack risk. They are even re-examining the nonprescription naproxen, another COX-2 sold as Aleve.
Although the expensive, heavily advertised prescription drugs are generally no more effective than over-the-counter painkillers for some ailments, the medications are important for certain patient groups.
For example, COX-2 inhibitors may be preferable to morphine in patients who have undergone noncardiac-related surgery, said Dr. Nancy Nussmeier, an anesthesiologist with the Texas Heart Institute at St. Luke’s Episcopal Hospital who led one study. Morphine can cause respiratory suppression and excessive sedation.
“Physicians will have to weigh the risk-benefit ratio of all these agents in a given patient and make a choice,” said Nussmeier, who is attending this week’s FDA meeting as a consultant to Pfizer, the maker of Bextra and Celebrex.
In addition, the drug class shows promise as a way to prevent some cancers, said Bresalier.
The Texas Heart Institute study looked at 1,671 coronary artery bypass patients randomly assigned to receive an intravenous COX-2 inhibitor followed by Bextra after surgery; or an intravenous placebo followed by Bextra; or a placebo alone.
All of the patients had access to standard opioid painkillers.
Cardiovascular events, including heart attack, cardiac arrest, stroke and pulmonary embolism, were frequent enough to raise “serious concern about the use of these drugs in such circumstances,” the researchers wrote.
Eighty patients in the COX-2 group suffered a cardiovascular problem, compared with 22 patients in the placebo group.
The study suggested that heart bypass patients might be at risk of adverse reactions to the drugs because all have clogged arteries.
Nussmeier said she will present at the meeting unpublished data from another study that showed patients given COX-2 drugs after orthopedic, gynecologic and other noncardiac-related surgeries did not seem to be at the same risk of cardiovascular events as the heart bypass group.
“There was no (danger) signal at all in that group,” Nussmeier said.
The study led by Bresalier was the largest designed to look at Vioxx as a way to prevent the regrowth of precancerous colon polyps in people who had already had polyps removed. The study compared 2,586 patients during three years; roughly half of the patients took Vioxx daily, and the others took a placebo.
“There was a significant reduction in patients who had recurrent polyps,” Bresalier said. “It was a positive study from that point of view.” However, Bresalier’s team halted the experiment nearly two months early when Merck pulled Vioxx on Sept. 30.
Analysis showed the risk of a heart attack or stroke was almost double in patients who received the drug, compared with those who took a placebo. Problems began appearing at the 18-month mark, Bresalier said.
Forty-six of the 1,287 patients who took Vioxx daily had a cardiovascular event during the three-year period. In the 1,299 patients given a placebo, there were 26 events. Each group had the same number of deaths and not all were related to heart attacks or strokes.
The Harvard study, which reviewed serious cardiovascular events among 2,035 patients taking Celebrex as part of a colon cancer prevention study, found elevated cardiovascular risk related to higher dosage.
Seven of 679 patients in the placebo group died from heart attacks, stroke or heart failure, compared with 16 of the 685 patients taking 200 milligrams of Celebrex twice daily and 23 of 671 patients taking 400 milligrams of Celebrex twice daily.
Source: The Associated Press contributed to this story.
MEDICATIONS
COX-2 inhibitors have been associated with increased risk of heart attacks and strokes.
–COX-2 inhibitors: Vioxx, Celebrex, Bextra and naproxen (sold over the counter as Aleve).
–www.fda.gov: For information about the FDA’s meeting on the risks and benefits of COX-2 inhibitors.
—–
To see more of the Houston Chronicle, or to subscribe to the newspaper, go to http://www.HoustonChronicle.com
(c) 2005, Houston Chronicle. Distributed by Knight Ridder/Tribune Business News. For information on republishing this content, contact us at (800) 661-2511 (U.S.), (213) 237-4914 (worldwide), fax (213) 237-6515, or e-mail reprints@krtinfo.com.