Some painkillers have more bleeding risk than others

NEW YORK (Reuters Health) - When it comes to gastrointestinal side effects, particularly bleeding into the stomach, not all painkillers known as non-steroidal anti-inflammatory drugs (NSAIDs) are created equal, new research shows.

“Balancing the safest NSAID with the most effective is always a trade off,” Dr. Luis A. Garcia Rodriguez of the Spanish Center for Pharmacoepidemiological Research in Madrid, one of the study’s authors, told Reuters Health via email.

For that reason, he added, people who need to use these drugs should choose those with the lowest gastrointestinal risks and use them for the shortest possible time at the lowest effective daily dose.

Stomach bleeding is a well-known risk factor of all NSAIDs, Garcia Rodriguez and his colleagues note in the journal Arthritis and Rheumatism. But the comparable risks of individual NSAIDs (such as ibuprofen), as well as those of newer NSAIDs called COX-2 inhibitors (like celecoxib, sold as Celebrex) are “still debated,” they add.

The newer drugs are designed to reduce gastrointestinal side effects. But the drugs have other problems: One, Vioxx (rofecoxib), was pulled from the market in 2004 after being linked to heart-related problems.

To investigate the relative gastrointestinal risks of traditional NSAIDs and newer ones, Garcia Rodriguez and his team reviewed the medical literature from 2000 to 2008, coming up with nine studies. All involved patients who had been hospitalized or sought a specialist’s care for gastrointestinal bleeding or torn gastrointestinal lining.

Past research has shown that the risk of developing these complications in people who are not taking prescription NSAIDs at all is low; there would be one such case for every 1,000 people every year in the general population, or about a tenth of a percent annual risk for an individual. But risk climbs as people age, and is also elevated for people with ulcers. For example, a man in his 70s with an ulcer would have a 4 percent risk of bleeding or tearing in a given year.

The researchers found that traditional NSAIDs upped the risk of gastrointestinal bleeding or torn stomach four-fold -- translating to a 16 percent annual risk for the hypothetical male ulcer patient in his 70s. Risk nearly doubled with COX-2 inhibitors, which would up the man’s annual risk of the complication to 8 percent.

Traditional NSAIDs were less risky at lower doses, for example up to 1,200 milligrams daily of ibuprofen, which is considered the maximum daily dose for over-the-counter use of the drug. People taking this much of the drug, or a comparable amount of other similar drugs, would more than double their risk of complications.

But higher doses -- such as 1,200 to 2,400 milligrams of ibuprofen daily -- meant a five-fold increased risk of bleeding or torn stomach lining. The risks went up immediately after patients began taking the drugs.

The lowest-risk individual drugs were ibuprofen (risk almost tripled), rofecoxib (risk doubled), aceclofenac (sold as Hifenac or Acetal, and carrying a 44 percent increased risk) and celecoxib (42 percent).

The highest risks were seen with ketorolac (a prescription NSAID sold as Toradol and Acular, with a more than 14-fold increased bleeding or perforation risk) and piroxicam (another prescription NSAID, sold as Feldene, with a nearly 10-fold greater risk).

Drugs that were active in the body for longer, either because they were slow-release formulations or took a longer time to be broken down, were riskier, the researchers found.

Drugs that are broken down quickly in the body and can be used at low doses, such as ibuprofen, as well as newer drugs such as celecoxib are the safest in terms of gastrointestinal bleeding, Garcia Rodriguez said. He added that older people and people who have had stomach ulcers are at particularly high risk of these side effects.

SOURCE: Arthritis and Rheumatism, online February 22, 2010.