The U.S. Food and Drug Administration (FDA) announced that it was halting the use of cox-2 inhibitor, Celebrex, in a clinical trial on colorectal cancer patients after a study found an apparent increase in the risk of heart attack among those taking the painkiller. Another government agency, the National Institutes of Health (NIH), said it would take a close look at all cox-2 inhibitors in an immediate review.

The swift action came hours after the drug giant Pfizer Inc. said it, too, was suspending new research on Celebrex, its popular drug.

Pfizer's announcement said a second, separate cancer trial found no increased risk of heart problems tied to the drug, urged that all patients "being treated with Celebrex should discuss appropriate treatment options with their health-care professionals."

Celebrex is similar to Vioxx, a cox-2 inhibitor made by Merck & Co. that was pulled from the market in September because of increased cardiovascular risks found in patients who were taking it for pain for more than 18 months.

The medical profession reaction was one of no surprise. "We knew this was coming," said Dr. Mark Fendrick, a professor of medicine at the University of Michigan School of Medicine. "Even if these drugs do remain on the market, given the availability of other therapies that provide equivalent pain relief and, if needed, equal levels of stomach protection, it would be extremely prudent to avoid these drugs until we know for sure-- and I emphasize for sure -- about their cardiovascular safety."

Pfizer said it was reviewing the data and warned against jumping to conclusions about the use of Celebrex for all patients. They reminded everyone that those patients enrolled in the two cancer trials were taking twice the dose recommended for people struggling with pain due to osteoarthritis.

The National Cancer Institute conducted both cancer trials. The APC trial, named Adenoma Prevention with Celecoxib (the generic name for Celebrex), uncovered the cardiovascular problems, while no problems have yet been determined by the trial named Prevention of Spontaneous Adenomatopus Polyps (PreSAP) trial.

"In placing this new information in context, it is important to understand that the APC trial results differ from both the PreSAP cardiovascular results as well as the large body of data that we and others have accumulated over time, in which an increased risk of serious cardiovascular events in arthritis patients, even at higher-than-recommended doses, had not been seen," said Dr. Joseph Feczko, president of worldwide development for Pfizer.

"These clinical trial results are new," added Hank McKinnell, Pfizer's chairman and chief executive officer. "The cardiovascular findings in one of the studies (APC) are unexpected and not consistent with the reported findings in the second study (PreSAP). Pfizer is taking immediate steps to fully understand the results and rapidly communicate new information to regulators, physicians and patients around the world."

Celebrex is approved in the United States for the treatment of arthritis and pain at recommended doses of 100 milligrams to 400 milligrams per day. It is also approved for a rare genetic condition known as familial adenomatous polyposis at doses up to 800 milligrams per day. The two cancer trials both used doses above the levels recommended for arthritis and pain: 400 milligrams to 800 milligrams in the APC trial, and 400 milligrams per day in the PreSAP trial. The two studies combined have enrolled about 3,600 participants, some of whom have been involved in the research for more than four years. Pfizer estimated that about 2,400 participants evaluated in the cardiovascular analysis had completed two years of treatment.

Patients in the APC trial were found to have about a 2.5 times higher risk of experiencing major fatal or non-fatal cardiovascular events compared to those patients taking a placebo, according to Pfizer.

The Data Safety and Monitoring Boards of both trials had conducted a preliminary review of data in September and October and decided to continue with the trials. The safety review boards then convened a panel of cardiovascular experts to conduct additional analysis. Pfizer received preliminary information from those reviews.

There is a third long-term study under way looking at Celebrex in patients at high risk for Alzheimer's disease. The study has about 2,000 patients, 750 of whom are on 400 milligrams of Celebrex daily. A review by a board of independent safety experts on Dec. 10, 2004 did not result in any recommendations to change the study.

Ever since Vioxx was pulled from the market in September 2004, health experts have been wondering whether the heart problems were unique to that drug or all cox-2 inhibitors. In November 2004, Pfizer's other cox-2 inhibitor drug, Bextra, had the strongest possible warning added to its label, highlighting the possibility of serious skin reactions and saying the drug should not be used in people who have had bypass surgery. Now, with the findings of the recent studies dealing with Celebrex, the class-wide effect seems to be likely. "In light of this discouraging news, individuals who are taking Celebrex or Bextra should immediately contact their physician."

Pfizer said it would continue working with the U.S. Food and Drug Administration on the company's plans to conduct a clinical trial to further assess Celebrex in individuals with osteoarthritis who are at high risk for cardiovascular disease.