The new generation of pain drugs is supposed to be easier on the stomach. But new data suggest that older pain drugs plus stomach-protecting drugs work better.
Newer pain drugs are called Cox-2 inhibitors. The family includes Vioxx, Bextra, and Celebrex. The drugs became widely popular because they were supposed to be safer than older pain drugs -- traditional non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen and naproxen. Ironically, Vioxx and Bextra were pulled from the market due to rare but potentially deadly heart side effects.
Yet clinical trials have shown that the Cox-2 inhibitors caused less stomach bleeding than the traditional NSAIDs. Now a new study -- which focused mainly on Vioxx -- shows that patients taking Cox-2 inhibitors had no fewer stomach bleeds or ulcers than those taking traditional NSAIDs.
The study appears in the Dec. 3 issue of BMJ.
The news isn't all bad, however. The researchers found that patients taking any kind of NSAID were able to avoid stomach bleeding and ulcers simply by combining them with stomach-protecting drugs.
Julia Hippisley-Cox, MD, and colleagues gathered information on 9,407 U.K. patients who suffered stomach bleeding or ulcers. They matched these patients to nearly 89,000 patients who didn't have stomach problems.
Patients were about one-and-a-half to two times more likely to have stomach problems if they were taking naproxen, aspirin, Vioxx, or ibuprofen. They did not find any stomach problems with Celebrex. But the study researchers downplay this finding because so few of the patients -- all treated between July 2000 and August 2004 -- took Celebrex.
Role of Cox-2 Drugs
But Cox-2 expert A. Mark Fendrick, MD, suggests that the patients who were given Cox-2 drugs had a higher risk of stomach problems to start with. Fendrick is professor of internal medicine and of health management and policy at the University of Michigan.
Patients with previous stomach problems are often given Cox-2 inhibitors instead of traditional NSAIDs. This could have skewed the findings, says Fendrick. "You could argue that the Cox-2 drugs were slightly better," he tells WebMD.
And a recent study found that doctors tend to prescribe Cox-2 drugs to patients who have a higher risk of stomach bleeds, says Harvard rheumatologist Lee Stuart Simon, MD. Simon recently finished a four-year stint as director of the branch of the FDA that monitors both the Cox-2 drugs and traditional NSAIDs.
"The question is, if a patient has pain and has a gastrointestinal risk -- beginning with age over 60, and then past history of ulcer, other drugs that cause bleeding risk, or being very frail and sick -- taking an NSAID adds up to a significant risk," Simon tells WebMD. "So if I saw a patient like that I would choose a [Cox-2 inhibitor] over a traditional NSAID."
Simon notes that stomach trouble isn't the only gastrointestinal problem caused by NSAIDs. The drugs also can cause bleeding in the intestines. And this, he says, has not yet been seen with Celebrex -- the only Cox-2 inhibitor still on the market.
Back-to-the-Future Pain Control
Significantly, Hippisley-Cox's team found that the risk of stomach problems went away if the patients took stomach-protecting drugs. That, Fendrick says, is the study's most significant result.
"If you really want to decrease the risk of NSAIDs, take stomach protection," Fendrick tells WebMD. "It is the back-to-the-future combination. Instead of a new drug that's supposed to have fewer stomach side effects, use a traditional NSAID with something that protects the stomach."
For stomach protection, Fendrick recommends the class of drugs called proton-pump inhibitors or PPIs. They are sold in over-the-counter versions, such as Prilosec, and in prescription versions, such as Aciphex, Nexium, and Prevacid.
Here's Fendrick's advice. If you have pain, are under age 60, have never had ulcers or gastrointestinal bleeding, and aren't taking a blood thinner or an oral steroid:
--If your heart risk is low and you don't need to take regular aspirin, consider a traditional NSAID such as ibuprofen (Advil, Motrin) or naproxen (Aleve, Nuprin). You might also get relief from acetaminophen (Tylenol), which is not an NSAID.
--If you have risk factors for heart disease -- a history of heart attack, stroke, or chest pain, high blood pressure, high cholesterol, or a family history of heart disease -- consider a non-NSAID such as acetaminophen, or an NSAID such as ibuprofen or naproxen. If you take aspirin, try a PPI. If you don't take aspirin, ask your doctor whether you should.
If you have pain, Fendrick says, are over 60, have ever had ulcers or gastrointestinal bleeding, or take a blood thinner or oral steroid:
--If your heart risk is low and you don't need regular aspirin, consider a non-NSAID such as acetaminophen. If needed, you could take a traditional NSAID plus a PPI to protect your stomach.
--If you have risk factors for heart disease, ask your doctor whether you should take acetaminophen or a different type of painkiller. If you take an NSAID, you must take a PPI for stomach protection. And if you're not on aspirin, ask your doctor whether you should be.
By Daniel J. DeNoon, Michael W. Smith, MD
SOURCES: Hippisley-Cox, J. BMJ, Dec. 3, 2005; vol 331: pp 1310-1312. Moride, Y. Arthritis Research & Therapy, 2005; vol 7: pp R333-R342. A. Mark Fendrick, MD, professor of internal medicine, School of Medicine, University of Michigan, Ann Arbor; professor of health management and policy, School of Public Health, University of Michigan, Ann Arbor. Lee Stuart Simon, MD, associate clinical professor of medicine, Harvard Medical School, Boston.