People in a study who took the arthritis drug rofecoxib (Vioxx) were 2.7 times as likely to have a heart attack as people who took a similar drug, celecoxib (Celebrex), according to research published online December 7 by the Annals of Internal Medicine. People who took nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen and naproxen had a lower heart-attack risk than those who took Vioxx. But Vioxx and Celebrex users had no greater risk than people who did not take NSAIDs.

People in a study who took the arthritis drug rofecoxib (Vioxx) were 2.7 times as likely to have a heart attack as people who took a similar drug, celecoxib (Celebrex), according to research published online December 7 by the Annals of Internal Medicine. People who took nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen and naproxen had a lower heart-attack risk than those who took Vioxx. But Vioxx and Celebrex users had no greater risk than people who did not take NSAIDs.

What Is The Doctor’s Reaction?

Since rofecoxib (Vioxx) was withdrawn from the market earlier this year, patients taking this medicine and their doctors have been in a state of limbo about what to do next. Should people who used to take Vioxx switch to the closely related celecoxib (Celebrex) or valdecoxib (Bextra)? Or, do these alternatives come with a similar increase in the risk of cardiovascular disease as Vioxx? No one knows for sure.

Now comes word that Celebrex may be much safer for the heart than Vioxx. By asking people who were hospitalized with a heart attack about their medication use and comparing their answers to those without a heart attack, researchers from the University of Pennsylvania School of Medicine made these observations:

 
• People taking Vioxx had a nearly threefold increase in the risk of heart attack compared with those taking Celebrex.  
• There was no significant increase in heart attack risk with either Vioxx or Celebrex compared with people who took no anti-inflammatory medicines. In fact, Celebrex appeared to decrease the risk.  
• Vioxx use was associated with an increase in heart attack risk when compared with older anti-inflammatory medicines (including aspirin, naproxen and ibuprofen) - not because Vioxx increased risk, but because these older agents were protective.

While news stories about this research have concentrated on the difference in risk between Vioxx and Celebrex, these findings may be more confusing than enlightening.

The increased cardiac risk associated with Vioxx in an earlier study and announced in September - findings that led to its withdrawal from the market - was not confirmed in this latest study. The only reason Vioxx had a higher risk than Celebrex was that Celebrex appeared to reduce risk.

These findings should provide some measure of reassurance for people taking Celebrex, but this will not resolve the debate about its safety. This study relied on the memory of patients after hospital admission, and patient memory is not always reliable.

In addition, only half of the eligible study patients completed interviews and the number of patients actually taking Celecoxib or Vioxx was relatively small.

Although we’ve been hearing a lot about the potential risks of the newer anti-inflammatory medications that are still available (Bextra and Celebrex), it’s worth considering their potential benefits.

They block inflammation and provide pain relief just as well as - though no better than - older agents. Their advantage over older medicines, such as ibuprofen and naproxen, however, is fewer ulcers and potentially fatal complications such as intestinal perforation, obstruction or hemorrhage. In recent months, these benefits have been largely overlooked as the debate about their safety has taken center stage.

It’s worth noting that even though the number of people taking anti-inflammatory medicines has increased in the last few years, the percentage of those people developing ulcers has decreased. This may be due, at least in part, to the decreased ulcer risk of the newer anti-inflammatory medicines, including Bextra and Celebrex.

For people with arthritis and a higher than average risk of ulcer disease (including those over 64, with previous ulcer disease, or use of corticosteroids), these medications have made a big difference. On the other hand, there’s no good reason for people at average or low risk of ulcer disease to be taking Celebrex or Bextra. It’s likely that they would do just as well with an older (and much cheaper) anti-inflammatory medicine.

What Changes Can I Make Now?

If you are still taking Vioxx, it’s probably best to discontinue the medication. I continue to see patients who had a large supply of the medicine when the recall was announced and continue to take it. That’s a particularly risky thing to do if you have heart disease or risk factors such as a history of smoking, diabetes, High cholesterol or a family history of heart disease.

If you are currently taking Celebrex or Bextra, talk with your doctor about your risk of heart and ulcer disease. Unless you have an increased risk of ulcer disease, there is no compelling reason to take either of these medications. It also makes sense to avoid these medicines if you have had cardiovascular disease in the past or have significant cardiovascular risk factors (as mentioned above), at least until more definitive evidence of safety is available.

For people taking these drugs, there are many other options to treat pain or arthritis, including:

 
• Non-medication approaches - Massage, heat, exercises and physical therapy are just a few of the ways to treat arthritis or other causes of pain without medicines.  
• Acetaminophen (Tylenol and others) - For the most common type of arthritis, osteoarthritis (degenerative joint disease), acetaminophen is recommended as the initial medication choice. For many people, it can provide significant pain relief and is generally considered safer than anti-inflammatory medicines.  
• An older anti-inflammatory medication taken with a medicine to protect the stomach - For people with risk factors for cardiovascular and ulcer disease, ibuprofen and omeprazole (Prilosec and others), or similar combinations, may be reasonable.  
• A trial of no treatment - One recent study found no long-term benefit from an anti-inflammatory medication among people with osteoarthritis. It may be worth reducing or stopping whichever anti-inflammatory medicine you take to see if there’s any difference without it. For minor aches and pains, many people choose to tolerate the symptoms without taking a medication. Talk to your doctor before stopping any medication he or she has recommended.  
• An entirely different class of medicine - Medicines other than anti-inflammatory medications may be helpful, depending on the type and cause of pain. Examples include muscle relaxants for muscle spasm, anti-seizure drugs for nerve disease, and medicines that modify the immune system for rheumatoid arthritis.

It may be time to change how you view medications. For many conditions, a pill may be somewhat helpful but will not provide complete relief nor cure the disease, especially for chronic illnesses including many types of arthritis.

All medicines have risk, and approval by the U.S. Food and Drug Administration (FDA)l is no guarantee of safety. One reason for this is that studies of several hundred, carefully selected research subjects cannot always predict a drug’s effect on millions of people taking them after FDA approval. People in “real life” inevitably differ from research subjects. And rare side effects will not be routinely detected in a study of several hundred subjects.

What Can I Expect Looking To The Future?

Though this new research is good news for Celebrex users, it will not end the debate about the drug’s safety. As for Bextra, there are still no conclusive studies about cardiovascular risk. You can expect to hear more about research that evaluates the risks and benefits of these drugs in the near future.

Important questions need to be answered.

 
• Is Celebrex use associated with a different risk of heart attacks (including fatal ones) as compared with Vioxx? What about the overall cardiovascular risk (including stroke) of Vioxx and Celebrex compared with other anti-inflammatory drugs?  
• If better studies find that the newer anti-inflammatory drugs (including Celebrex and Bextra) are associated with an increased risk of heart attack or stroke compared with older drugs, is it because the newer drugs promote these problems or because they lack the protective effect of the older drugs?  
• Is a person who has an above average risk of ulcer disease but an average risk of heart disease better off taking Celebrex (or Bextra) than ibuprofen? That is, are there people for whom the gastrointestinal benefits clearly outweigh the cardiovascular risks? Similarly, how does the use of Celebrex (or Bextra) compare with the combination of ibuprofen and omeprazole (or other, similar combinations)?  
• Is Celebrex actually protective against heart attack, as suggested in this latest research? If so, is it more protective than naproxen or other, older agents?

When additional studies provide answers to these questions, it is likely that experts will develop clearer guidelines about the use of the newer anti-inflammatory agents, Celebrex and Bextra.

My guess is that in the future, these drugs will be used more selectively, limited to those who have the most to gain (people with a risk of ulcer disease) and avoided in those most likely to have problems (those with excess cardiovascular risk).

But that’s only if additional research finds that these medicines are acceptably safe for the cardiovascular system. If it turns out that the risk of heart attack or stroke is raised by these medicines, they could get withdrawn from the market just as Vioxx was. Only time - and additional study - will tell.