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Effects and Prevention of Chronic NSAID Use on the Stomach

1 August 2008


Purpose: As our population continues to age, the prevalence of nonspecific nonsteroidal anti-inflammatory drugs (nsNSAID) and cyclooxygenase-2 (COX-2) inhibitor use increases. Each year approximately 3,200 to >16,500 deaths are attributed to gastrointestinal (GI) toxicity secondary to NSAID use. With the growing concern of the damage these medications can do to the gastric mucosa, the prevention of GI injury is an important clinical issue. The purpose of this review was to determine the current recommendations for prescribing nsNSAID and COX-2 inhibitor drugs in relation to minimizing GI injury.

Methods: An extensive literature review in English was performed searching for articles over the past 10 years using terms related to NSAIDS and GI complications Articles were rejected if the study was not a randomized controlled trial or retrospective cohort trial; included exclusively children; lasted less than 21 days; or did not measure review outcomes.

Results: NSAID vs COX-2 – Three randomized controlled trials demonstrated the same result: COX-2 selective inhibitors were associated with less significant GI effects than nsNSAIDs alone. However, two out of the three tests came under scrutiny and the results were thought to be biased and not completely reported. COX-2 vs. NSAID plus PPI - Studies found that a COX-2 inhibitor was as effective as an NSAID plus a PPI with respect to the prevention of recurrent bleeding. However, the studies agreed that even though the two methods were as effective, the risk of recurrent bleeding with either treatment was high, suggesting that neither regimen could completely protect patients at high risk from recurrent ulcer complications. COX-2 vs. COX-2 plus PPI – Studies determined that combination treatment was more effective then COX-2 inhibitors alone, for the prevention of ulcer bleeding in patients at high risk. The study defined high risk as patients with a previous history of ulcer bleeding. A limitation noted in a study was the inability to assess the best possible management for patients with high cardiovascular risk and therefore the role of concomitant aspirin in relation to the efficacy of COX-2 inhibitors. NSADI plus PPI vs. COX-s plus PPI – The VENUS and PLUTO studies were conducted at the same time and both concluded that significant reductions in ulcer development were observed for users of both nsNSAIDs and COX-2 inhibitors in combination with a PPI. However, the trial sizes were of significant difference and the percentage of patients in the VENUS study that had a history of ulcer as their sole risk factor was significantly lower than in the PLUTO group.

Conclusion: Many of early studies on COX-2 inhibitors were done by the drug companies themselves, and therefore contained biased information. In the recent years, viable data has emerged to help us make decisions about the proper care for our chronic NSAID-use patients. Upper GI injury while taking aspirin or NSAID’s is typically related to risk factors, dosages and duration spent taking the drug. Therefore, the smaller the dose and the less time spent on the drug will help decrease the risk of developing some sort of GI injury. In the instance where a patient will need to take chronic NSAID therapy, it is recommended a patient with no cardiovascular risks (not taking aspirin) and with no or low risk of GI factors should take an nsNSAID. If a patient with no cardiovascular risks has GI risks then it is recommended they take either a COX2 or an nsNSAID with a PPI. Patients with cardiovascular risks and no GI risk should take nsNSAIDs with a PPI only if GI risks warrant it. A patient with both cardiovascular and GI risks should take a nsNSAID with a PPI.


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