Ranking NSAIDs According To GI Risk

Throughout my career, I have had various clinicians develop trends in the NSAID that they prefer to use. Why do we choose ibuprofen versus diclofenac versus piroxicam? In this post, I will be ranking NSAIDs according to their GI risk based upon the literature we have. This may help explain why we choose one NSAID versus another in high GI risk patients.

Let’s first start with the elephant in the room. Why not celecoxib? This is absolutely a consideration and is low GI risk compared to traditional NSAIDs. Some clinicians do get worried with celecoxib over the cardiovascular risks and thus will avoid it in select patients. I won’t get into the cardiovascular side of things in this post, but medications and ALL of their adverse effect profiles need to be assessed in each individual patient.

Let’s create a scenario where you have a provider that approaches you and is asking for a recommendation about which NSAID to use. They want to avoid celecoxib. Acetaminophen, opioids, and other analgesics are not an option. This patient has a GI bleed history and the provider is going to put them on GI protection.

One of my most important, and easy recommendations is to ensure that we use the minimum effective dose. The clinician will likely weigh this with the severity of the pain they are trying to treat. If at all possible, I would encourage trying to start at a low dose because it has been well proven that GI risks increase as the dose increases.

Ranking NSAIDs According to GI Risk

Alright, you’ve waited long enough. Let’s continue to think about that situation where an NSAID is going to be chosen. Which one should we pick? One of the most famous NSAID risk studies was by Richy et. al. You can find the abstract link here. Essentially, here’s what they found from lowest GI risk to highest GI risk:

  1. Ibuprofen
  2. Meloxicam
  3. Tenoxicam (I’ve never seen in practice)
  4. Piroxicam
  5. Diclofenac
  6. Naproxen
  7. Indomethacin

In another study (meta-analysis) by Bhala et al, that included diclofenac, ibuprofen, and naproxen, it was determined that diclofenac was the lowest risk, followed by ibuprofen and naproxen.

Based on this evidence I’m typically going to recommend ibuprofen or meloxicam. Diclofenac has some mixed evidence that is hard to decipher but may be considered. Patient preferences such as desired frequency of dosing and previous experience will of course play a role in guiding therapy. If they have tried ibuprofen and not had success, we would likely avoid it. If they haven’t tried it, the accessibility of having it over the counter is a nice advantage compared to diclofenac or meloxicam.

I would 100% avoid indomethacin which most clinicians do in my experience due to GI risk. Ketorolac was not included in either study above but is considered a high GI risk NSAID. It actually carries a boxed warning for GI risk when used for greater than 5 days. I would avoid ketorolac as well.

What do you think and what have you seen in your experience when it comes to ranking NSAIDs according to GI risk?

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Written By Eric Christianson

April 20, 2022

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