Taking low-dose aspirin and NSAIDs can be a challenge (Part 2)

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Taking low-dose aspirin and NSAIDs can be a challenge (Part 2)

In a previous blog, “Taking low-dose aspirin and NSAIDs can be a challenge – (Part 1),” I wrote:

  • I have many patients who are taking low-dose (81 mg) aspirin (ASA) daily and who wonder if they can take a Non-Steroidal Ant-Iinflammatory Drug (NSAID) such as ibuprofen (Advil, Motrin) or naproxen (Aleve) for pain or fever. I warn them that adding an NSAID increases their gastrointestinal (GI) risk … and can possibly increase their cardiovascular (CV) risk.

I added:

  • NSAIDs with COX-1 activity (naproxen, ibuprofen, etc) seem to have a lower cardiovascular risk than those with more COX-2 activity (celecoxib, diclofenac, etc).

A representative from Pfizer, the manufacturer of Celebrex (celecoxib) wrote:

  • Please check the information on your article on NSAIDs and ASA. Updated information shows that Celebrex is LESS likely to cause CV events than traditional NSAIDs and does NOT intefere with the synthesis of ASA. Some studies in Europe show astronomically higher (2.8 FOLD) greater chance of a CV event with traditional NSAIDs vs Celexicob. Consider me an enthusiastic reader of your Webpage.

My initial response was this:

  • Thanks for the note. Since the information in this particular blog came from the PharmDs at the Prescriber’s Letter, let me run your feedback by them. Will let you know what I learn. Deeply appreciate your feedback and support.

I sent this inquiry to the experts at Prescriber’s Letter who investigated and have just written me this:

  • I went back and checked my references. The 2 key ones were dated 2009 and 2010, so I checked a new meta-analysis I knew had been published since our article. Based on available data, Celebrex is NOT proven to have less cardiovascular risk than naproxen or ibuprofen.
  • Based on numerous meta-analyses of RCTs and observational studies, naproxen is the least CV risky in the NSAID/COX-2 group, but ibuprofen is not too far behind.
  • In the most recent meta-analysis, ibuprofen and Celebrex were pretty close in their overall risk (ie, Celebrex was NOT clearly less risky). One limitation is that available meta-analyses are pooling results from trials that weren’t always primarily designed to assess CV risk as an outcome, but multiple meta-analyses have shown pretty consistent results.
  • There is a large (N=21,000) patient outcomes study that is prospectively comparing CV risk with Celebrex, naproxen, and ibuprofen underway, so perhaps in the future we’ll have an even more definitive information.
  • I do agree with the statement about Celebrex not interfering with aspirin, but that’s about it. I also checked with my top consultant in this area and he says the statement from the Pfizer rep (above) is simply incorrect.

So, until more data are available, I’ll need to stick to my recommendation to you, dear reader:
NSAIDs with COX-1 activity (naproxen, ibuprofen, etc) seem to have a lower cardiovascular risk than those with more COX-2 activity (celecoxib, diclofenac, etc).



  1. Annette says:

    So, Walt, does this mean that any amount of ibuprofen is some risk for CV event? Even one or two gelcaps a week?

    • waltlarimore says:

      These warnings apply to folks taking CHRONIC NSAIDs.
      Nevertheless, many are concerned. Since the withdrawal of Vioxx (rofecoxib) and Bextra (valdecoxib) from the market due to cardiovascular risks, there has been a great interest in the cardiovascular safety of traditional NSAIDs.
      As I mention in the blog posts, contrary to previous belief, naproxen (Alleve, Naprosyn, etc) was found to have neutral effect on the cardiovascular system in both large meta-analyses published to date.
      For those who require an NSAID for chronic pain relief, naproxen appears to be the safest from a cardiovascular perspective. If adverse gastrointestinal effects are of concern, naproxen plus a proton pump inhibitor may be considered.
      Folks should take the lowest effective NSAID or COX-2 inhibitor dose to minimize cardiovascular or gastrointestinal adverse events.
      In those who take aspirin for cardioprotection AND require chronic pain management, consider using a non-NSAID product (e.g., acetaminophen). If ibuprofen as a single dose is used concomitantly with aspirin, then experts say to take ibuprofen either eight hours before or 30 minutes after the immediate-release aspirin dose. It is best to avoid multiple ibuprofen dosing with aspirin use.
      Hope this helps.

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