Celecoxib (CELEBREX) May Double the Risk for Heart Attacks Compared to Older Arthritis Drugs

New research published in the March 2006 edition of the Journal of the Royal Society of Medicine indicates that the popular arthritis and painkilling drug celecoxib (CELEBREX) may double the risk for heart attacks compared to older arthritis medications. The research was conducted by New Zealand’s Medical Research Institute.

Celecoxib is produced by a division of Pfizer, Inc. and was approved by the Food and Drug Administration (FDA) in December 1998. In 2005, there were almost 11 million prescriptions dispensed for the drug in U.S. pharmacies, accounting for more than $1.2 billion in sales. Thankfully, the number of prescriptions and retail sales are off about 40 percent compared to 2004.

Celecoxib’s image as a better and safer drug for arthritis was fashioned around the theory that it is a specific inhibitor of cyclooxygenase-2 or COX-2 for short. All nonsteroidal anti-inflamammtory drugs (NSAIDs) work by inhibiting the COX enzymes. Two forms of this enzyme are known to exist, COX-1 and COX-2. In theory, both COX-1 and COX-2 reduce the symptoms of arthritis but also lead to the adverse effects associated with NSAIDs. If COX-2 were selectively blocked, the reasoning goes, arthritis pain would be relieved without the serious GI and other adverse effects seen with the use of NSAIDs. Unfortunately, this theory has never been proven in well done clinical trials looking at serious gastrointestinal toxicity. Examples of NSAIDs that do not selectively block the COX-2 enzyme include ibuprofen (MOTRIN) and meloxicam (MOBIC).

The possibility that celecoxib could increase the risk of cardiovascular toxicity was raised in an editorial published in the Sept. 13, 2000 issue of the Journal of American Medical Association. The editorial’s authors wrote that: “In theory, COX-2-selective inhibitors might increase the risk for thromboembolic cardiovascular events [blood clots in the heart that cause heart attacks] ....”

In January 2005, the Health Research Group petitioned the FDA to immediately remove celecoxib and its close chemical cousin valdecoxib (BEXTRA) from the market.

Valdecoxib was finally removed from the market in April 2005 (see Worst Pills, Best Pills NewsJune 2005 ).  Rofecoxib (VIOXX), another drug related to celecoxib and valdecoxib, was removed from the market earlier in September 2004 (see Worst Pills, Best Pills News November 2004 ).

The New Zealand research was not based on just one  “gold standard” randomized controlled clinical trial. Rather, it was a statistical summary of a number of clinical trials called a meta-analysis. The research mathematically combined the results of six clinical trials that reported cardiovascular adverse reactions with celecoxib.

The four randomized controlled clinical trials included in the meta-analysis involved 4,422 patients. The meta-analysis found a 2.26-fold greater risk for heart attack with celecoxib compared to a placebo.  

The researchers also reported that in all six studies in the meta-analysis, there was an almost two-fold increase in the risk of heart attacks in patients given celecoxib. The studies analyzed included 12,780 patients and compared the number of heart attacks in patients using celecoxib, placebo, diclofenac (VOLTAREN), ibuprofen (MOTRIN), and acetaminophen (TYLENOL).  

The New Zealand authors concluded that:

This finding would suggest that the preferential risk/benefit assessment afforded celecoxib over other COX-2 inhibitors [rofecoxib and valdecoxib] by the FDA may not be supported by the currently available evidence.

In other words, the researchers are saying that celecoxib should be considered as dangerous as rofecoxib and valdecoxib, which were removed from the market. This is a position that we clearly support.

The FDA black box warning now in the professional product label for celecoxib appears at the beginning of this article.  A similar black box warning is in the professional product label of each NSAID sold in the U.S., with the exception of aspirin.  

The FDA has also required that information written specifically for consumers be distributed with all new and refill prescriptions for celecoxib and the other NSAIDs now on the market. This FDA-approved drug information for the public is called a Medication Guide. The NSAID Medication Guide can be found online. 

At this time, this is the best evidence available about the risks of celecoxib compared to other older arthritis drugs. A large randomized controlled trial looking at cardiovascular safety of celecoxib will be undertaken in the near future by the Cleveland Clinic. The results of this trial will provide “gold standard” evidence about the safety of celecoxib. Until the results of this study are published, you should avoid the use of this drug.

What You Can Do

You should not use celecoxib. The best evidence at this time indicates that the older drugs such as naproxen, ibuprofen, and acetaminophen are safer for the heart.