The COX-2 inhibitors Vioxx, Celebrex and Bextra were specifically developed to minimize the risk of stomach bleeding and ulcers associated with traditional drugs in the same NSAID family (e.g., aspirin, ibuprofen, naproxen).

Now it seems there’s a cardiovascular price to pay for this extra measure of stomach safety.

It should be said the negative news on Celebrex is based on research using higher doses (400 to 800 mg daily). Bextra, made by the Celebrex manufacturer, also appears to carry a cardiovascular price tag.

It’s important to realize the increased cardiovascular risk for any individual (absolute risk) taking a COX-2 inhibitor is small, and is likely to go away after the drug is stopped.

What exactly is it about these drugs that might increase the risk of heart attack and stroke? A simplified pharmacology lesson offers clues.

COX is an enzyme produced by the body in two forms, COX-1 and COX-2. Both affect blood platelets, cells that enable the blood to clot.

Traditional NSAIDs block both COX forms. COX-2 inhibitors specifically target COX-2 over COX-1.

Blocking COX-1 suppresses the formation of blood clots, while blocking COX-2 supports the formation of blood clots. Traditional NSAIDs, which block both COX forms, would tend to have a neutral effect on cardiovascular risk.

COX-2 inhibitors could tip the balance in favor of blood clot formation and thus promote heart attack or stroke.

Increased cardiovascular risk might be related both to degree of COX-2 blockade and to dose. Vioxx and Bextra are stronger blockers of COX-2 than Celebrex. But higher doses of Celebrex could increase its effect on COX-2.

Additionally, both traditional NSAIDs and COX-2 inhibitors tend to cause fluid retention and increased blood pressure. This could also factor into the increased cardiovascular risk observed with COX-2 agents.

What are alternatives to COX-2 inhibitors?

Doctors are once again embracing traditional NSAIDs, but prescribing those that appear to be less harsh on the stomach (e.g., Mobic, Relafen, Lodine, Motrin).

For those at high risk for stomach ulcers, a stomach-protective agent can be used with the NSAID.

Aspirin-related agents such as salsalate and magnesium salicylate may also be stomach-friendlier.

And don’t forget the old standby acetaminophen (e.g., Tylenol).

A natural option for osteoarthritis is glucosamine alone or combined with chondroitin.

Ask your doctor or pharmacist for help in choosing the best option.