Traditional Nsaid With Proton Pump Inhibitor is Better Than Even Newer Cox-2 Inhibitors for Patients With Risk of Heart Attack and Stroke

Traditional Nsaid With Proton Pump Inhibitor is Better Than Even Newer Cox-2 Inh

Although individual reactions to particular NSAIDs vary, in general the efficacy of COX-2 inhibitors has proved similar to that of other NSAIDs, as expected since both classes of drug inhibit the desired target, the action of COX-2 prostaglandins. The drugs's effectiveness is similar to that of traditional NSAIDs such as ibuprofen, diclofenac, or naproxen.


NSAIDs prevent the body from producing prostaglandins, which have been identified as a cause of pain and inflammation. They do this by inhibiting the COX (cyclo-oxygenase) enzymes that are important in the formation of prostaglandins by cells. By reducing the level of prostaglandins in your body, NSAIDs help relieve pain from conditions like arthritis. They also help reduce inflammation (swelling), lower fevers and prevent blood from clotting.

You have 2 types of COX enzymes in your body: COX-1 and COX-2. Researchers believe that one of the jobs of COX-1 enzymes is to help protect your stomach lining. The COX-2 enzyme doesn't play a role in protecting your stomach.

Traditional NSAIDs stop both COX-1 and COX- 2 enzymes from doing their jobs. When COX-1 enzymes are blocked, pain and inflammation is reduced, but the protective lining of your stomach is also reduced. This can cause problems such as upset stomach, ulcers and bleeding in your stomach and intestines.

COX-2 inhibitors only stop COX-2 enzymes from working. Since the COX-2 enzyme doesn't help to protect your stomach, COX-2 inhibitors may be less likely to irritate your stomach or intestines.

According to the Food and Drug Administration (FDA), Bextra (COX-2 inhibitors) was taken off the market because of:

*Insufficient data on the cardiovascular safety of long-term use of Bextra, along with the increased risk of adverse cardiovascular events in short-term coronary artery bypass surgery trials. These cardiovascular events may be associated with chronic use of Bextra.
*Reports of serious and potentially life-threatening skin reactions — Stevens-Johnson syndrome and toxic epidermal necrolysis with sloughing of the skin — in people using Bextra.
*Lack of any demonstrated advantages in using Bextra when compared with other NSAIDs.

Celebrex, like Vioxx and Bextra, is a COX-2 inhibitor. COX-2 inhibitors don't cause the stomach bleeding and ulcers that traditional nonsteroidal anti-inflammatory drugs (NSAIDs) might. If you're susceptible to gastrointestinal bleeding or ulcers, Celebrex may be a safe and appropriate treatment for you. Celebrex also might be an appropriate choice if you take drugs that contain prednisone. Those drugs, like NSAIDs, can cause stomach bleeding. To take traditional NSAIDs on top of those drugs would further increase your risk of bleeding.

A search for COX-2-specific inhibitors resulted in promising candidates such as valdecoxib, celecoxib, and rofecoxib, marketed under the brand names Bextra, Celebrex, and Vioxx respectively. Bextra and Vioxx are about 300 times more potent at inhibiting COX-2, than COX-1, suggesting the possibility of relief from pain and inflammation, without gastrointestinal irritation, and promising to be a boon for those who had experienced such adverse effects previously or had comorbidities that could lead to such complications. Celebrex is approximately 30 times more potent at inhbiting COX-2 than COX-1.

A new cox-2 painkiller called etoricoxib causes fewer upper gastrointestinal problems than the traditional pain medicine diclofenac, researchers report.

"In the trial, there was a difference in the overall events between the two drugs," said lead researcher Dr. Loren Laine, a professor of medicine at the University of Southern California Keck School of Medicine. "There was not a significant difference seen in the more serious and less common events, like major bleeding. The difference was largely seen in the uncomplicated ulcers, which are symptomatic but not generally life-threatening."

Etoricoxib (brand name Arcoxia) is a cox-2 inhibitor that has not been approved for use in the United States yet, although it is being used in Europe. Cox-2 drugs, such as Celebrex, Vioxx and Bextra, were developed to be less damaging to the stomach and intestinal tract. But, several of the cox-2 drugs have been linked to an increased risk of heart attack and stroke. As a result, Vioxx and Bextra were pulled from the market in 2004 and 2005, respectively. Celebrex is the only cox-2 inhibitor available to consumers. Etoricoxib is made by Merck & Co., the maker of Vioxx.

Diclofenac is a nonsteroidal anti-inflammatory (NSAID). NSAIDs such as diclofenac and aspirin are associated with gastrointestinal side effects, such as bleeding ulcers, when taken for an extended period.

In the new study, Laine and his colleagues analyzed data from three clinical trials, in which 34,701 arthritis patients were treated with etoricoxib or diclofenac. The patients were allowed to take additional medications called proton pump inhibitors, like Prilosec, to protect against gastrointestinal problems. In addition, patients with risk factors for heart attacks were allowed to take aspirin, which protects the heart.

The researchers found that upper gastrointestinal problems were significantly less common with etoricoxib than with diclofenac. But, more serious gastrointestinal events, such as major bleeding, were the same in both groups. The effects of etoricoxib or diclofenac did not differ significantly in people using proton pump inhibitors or aspirin.

Laine said all cox-2 inhibitors carry a risk of heart attack and stroke. "One wouldn't expect this one (etoricoxib) to be different," he said. "But it could provide another option for patients."

The new trial was done as part of the U.S. Food and Drug Administration's approval process, Laine noted.

Dr. Joost Drenth, of Radboud University Nijmegen Medical Center, the Netherlands, and author of an accompanying editorial in the journal, said there wasn't enough difference between the drugs in terms of gastrointestinal toxicity to show that etoricoxib was better.

"My advice would be to fall back to the good, old, classic NSAIDs with the addition of a proton pump inhibitor. Because we know adding a proton pump inhibitor to NSAIDs will decrease the incidence of dyspepsia," he said.

Another expert thinks etoricoxib and diclofenac are really two similar drugs, because diclofenac acts very much like a cox-2 inhibitor.

"It's not surprising that you don't see much of a difference when you compare Coke and Pepsi," said Dr. James M. Scheiman, a professor of medicine at the University of Michigan Medical Center.

Scheiman thinks the main concern with cox-2 inhibitors is weighing the cardiac risks with the gastrointestinal risks. "Which drug a patient should take is entirely driven by their underlying cardiac and gastrointestinal risk," he said. "Cox-2 inhibitors have a clear advantage on the gastrointestinal side when compared to drugs that aren't cox-2 inhibitors."

Dr. Mark Fendrick, a professor of internal medicine at the University of Michigan School of Medicine, agreed. "If you have cardiovascular concerns and no gastrointestinal risk, I would avoid the cox-2 inhibitors like the plague," he said.

"If you had a prior ulcer and can't tolerate Tylenol, and are lucky enough not to have any cardiovascular risk, then I would lean toward a cox-2 inhibitor or a traditional NSAID and a proton pump inhibitor," Fendrick said. "If you have both risks, then I would use acetaminophen or low-dose narcotics or a more cardiac safe NSAID, like Naproxen, and a proton pump inhibitor."

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