Drug combo prevents NSAID-related GI disturbance

Although all of the common strategies protect the upper gastrointestinal tract from the complications of nonsteroidal anti-inflammatory drugs (NSAIDs), popular over-the-counter analgesics such as Motrin (ibuprofen) or Aleve (naproxen), the combination of a COX-2 inhibitor and a proton pump inhibitor is associated with the largest reduction in gastrointestinal complications, according to a Canadian study published in the medical journal Gastroenterology.

COX-2 inhibitors treat pain and inflammation by selectively blocking the COX-2 enzyme, which prevents the production of chemical messengers that cause pain and swelling. They include drugs such as Celebrex (celecoxib). Two other COX-2 inhibitors (Vioxx and Bextra) were taken off the market in the U.S. because of safety concerns.

NSAIDs are non-specific inhibitors and also block chemical messengers that protect the stomach and play a role in blood clotting. Therefore, these drugs can cause bleeding and stomach irritation.

Proton pump inhibitors, such as Nexium (esomeprazole) and Prilosec (omeprazole), are a class of drugs that lower gastric acid levels. They are used to treat gastric disturbances and ulcers caused by the production of excessive gastric acid.

Using Manitoba’s province-wide health database, the researchers, led by Dr. Laura Targownik of the University of Manitoba, Winnipeg, identified 1,382 users of either NSAIDs or COX-2-specific NSAIDs who had been hospitalized for an upper gastrointestinal condition from October 1995 through March 2004. Each subject was then matched for age and gender with as many comparison subjects or “controls” as possible from the database.

Compared with using a NSAID alone, the strategy of using a COX-2 inhibitor plus a proton pump inhibitor produced the greatest risk reduction in upper gastrointestinal complications - by 64 percent. This was followed by COX-2 inhibitor alone (49 percent), then non-selective NSAID plus proton pump inhibitor plus any dose of misoprostol (42 percent), non-selective NSAID plus proton pump inhibitor (33 percent), and lastly non-selective NSAID plus low-dose misoprostol (26 percent) also know by the trade name Cytotec.

The combination of proton pump inhibitors and COX-2 inhibitors is the most effective approach, Targownik told Reuters Health. “Celecoxib seems especially protective, and given the relatively weak evidence (compared with other COX-2 inhibitors) of its being associated with cardiovascular complications, its use should be more strongly considered.”

In an accompanying editorial, Dr. David Y. Graham of the Baylor College of Medicine, Houston, and Dr. Francis K.L. Chan of the Chinese University of Hong Kong emphasize the importance of assessing a patient’s risk of gastrointestinal and other complications. They noted, for example, that the Canadian results “are consistent with the notion that no form of NSAID therapy should be used in patients with high gastrointestinal and high cardiovascular risk.”

SOURCE: Gastroenterology, April 2008.