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Risk of GI Bleeding Varies by NSAID Type, Dosage

Slow-release formulations and COX-1 plus COX-2 inhibition linked to increased risk of bleeding

WEDNESDAY, June 2 (HealthDay News) -- The risk of gastrointestinal (GI) complications due to nonsteroidal anti-inflammatory drug (NSAID) use varies by the specific drug used and by dosage, and those with a slow-release formulation or long half-life are associated with a greater risk, according to research published in the June issue of Arthritis & Rheumatism.

Elvira L. Massó González, of the Spanish Centre for Pharmacoepidemiological Research in Madrid, Spain, and colleagues conducted a systematic review of observational studies from 2000 to 2008 on NSAIDs and upper GI bleeding or perforation.

The relative risk of upper GI bleeding/perforation was 4.50 for traditional NSAIDs and 1.88 for coxibs. Relative risks varied widely for specific drugs: ibuprofen, 2.69; rofecoxib, 2.12; aceclofenac, 1.44; celecoxib, 1.42; ketorolac, 14.54; piroxicam, 9.94; naproxen, 5.63; ketoprofen, 5.57; indomethacin, 5.40; meloxicam, 4.15; and diclofenac, 3.98. NSAIDs with a longer plasma half-life or extended-release formulations and those that inhibited both COX-1 and COX-2 were associated with a higher risk of upper GI bleeding/perforation.

"We showed that persistent exposure to the drug is an important independent determinant; in fact, drugs with a long half-life or slow-release formulation were associated overall with a greater risk than NSAIDs with a short half-life," the authors write. "We observed the lowest GI toxicity with coxibs, i.e., celecoxib and rofecoxib, which supports the notion that sparing of COX-1 in the GI tract and possibly in platelets translates clinically to a lower risk of upper GI bleeding/perforation."

One of the authors disclosed financial relationships with the pharmaceutical industry.

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