In Search of Safer NSAIDs: Which Cause the Least Risk of Upper GI Bleeding?
In Search of Safer NSAIDs: Which Cause the Least Risk of Upper GI Bleeding?
Abstract & Commentary
By Joseph E. Scherger, MD, MPH, Clinical Professor, University of California, San Diego. Dr. Scherger reports no financial relationship to this field of study.
Synopsis: A systematic review of 9 studies showed that the COX-2 inhibitor celecoxib and ibuprofen cause less upper GI bleeding than other NSAIDs. Diclofenac, meloxicam, ketoprofen, indomethacin, and naproxen have intermediate risk. Piroxicam and ketorolac have the highest risk. In general, drugs that have a long half-life or slow-release formulation have the greatest risk of GI bleeding.
Source: Masso Gonzalez EL, et al. Variability among nonsteroidal antiinflammatory drugs in risk of upper gastrointestinal bleeding. Arthritis Rheum 2010;62:1568-1570.
A study group from Madrid, Spain, conducted a systematic review of cohort and case-control studies to look at the relative risk of upper GI bleeding or perforation among available nonsteroidal anti-inflammatory drugs (NSAIDs). Nine studies between 2000 and 2008 with more than 50,000 patients were used in the analysis.
The relative risk (RR) overall for NSAIDs causing upper GI bleeding or perforation was 4.50 for traditional NSAIDs and 1.88 for COX-2 inhibitors. Looking at specific drugs in increasing risk order, the relative risk with celecoxib (Celebrex®) was 1.42, ibuprofen (Motrin® and others) 2.69, diclofenac (Voltaren®) 3.36, indomethacin (Indocin®) 4.15, ketoprofen (Orudis® or Oruvail®) 5.40, naproxen (Aleve® or Naprosyn®) 5.57, piroxicam (Feldene®) 9.94, and ketorolac (Toradol®) 14.54.
Among the traditional NSAIDs, the longer-acting formulations cause the greater risk overall. The risk is highest during the first 30 days of use (RR, 5.22) and lower after more than 1 year of treatment (RR, 2.90).
Commentary
Not all NSAIDs are the same with respect to the risk for upper GI bleeding. This study, the largest to date, confirms the relative safety of the COX-2 inhibitors, with celecoxib being the only one available in the United States. There is still risk of bleeding, but much less than with traditional NSAIDs. I did not appreciate the greater than usual danger associated with the use of the IM medication ketorolac. I will be more mindful of this risk, especially with seniors.
Piroxicam probably should not be used unless a patient is doing well on it. I use a lot of naproxen and will reconsider that. Although in the intermediate risk category, it is riskier than most other NSAIDs. For short-term pain relief, ibuprofen remains a good choice. For long-term needs, the cost of celecoxib may well be worth it, especially in seniors who are more vulnerable to GI bleeding. Diclofenac looks like a good choice for chronic use of a traditional NSAID. A surprise for me in this study was the relative safety of indomethacin. I had always thought that this was a harsher medication on the stomach than other NSAIDs.
We want to always act in the best interest of our patients, and avoiding GI bleeding is of paramount importance when prescribing NSAIDs. I will keep these study results in mind and share them with patients when making treatment decisions for osteoarthritis and other conditions where NSAIDs are commonly used.
A systematic review of 9 studies showed that the COX-2 inhibitor celecoxib and ibuprofen cause less upper GI bleeding than other NSAIDs. Diclofenac, meloxicam, ketoprofen, indomethacin, and naproxen have intermediate risk. Piroxicam and ketorolac have the highest risk. In general, drugs that have a long half-life or slow-release formulation have the greatest risk of GI bleeding.Subscribe Now for Access
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