Sunday, May 1, 2011

Are Plavix and PPI Medicines Safe Together? The Surrogate Marker Strikes Again!

When the medical press seizes a story, it can become an obsession. Any physician who is reading any journal is aware of the reported interaction between clopidrogel (Plavix) and proton pump inhibitor (PPI) drugs, including Prilosec and her cousins. PPI medicines are not exotic elixirs known only to medical professionals. They are known to any person with a working TV set or who still reads a newspaper, since ads for these drugs are omnipresent. Just google ‘purple pill’ and begin your entrance into the PPI Chamber of Advertising.
PPI medicines are highly effective for peptic ulcers and gastroesophageal reflux, although I suspect that most patients on these medications do not have any true indication for them. (Disclosure: I’ve pulled the PPI trigger too quickly on many patients who do clearly require acid blocking medicines.) PPI medicines are prescribed to hospitalized patients almost by reflex, and are often administered by the intravenous route, even when patients can swallow pills adequately.

Medical studies in 2009 reported that PPI medications appeared to make Plavix less effective. Since thousands of patients are on both of these medicines, this drug interaction could affect a large cohort of patients. Plavix serves to keep coronary stents open and to prevent heart attacks and strokes. Clearly, any force that could diminish Plavix’s potency could have serious ramifications for patients. But, is it really true?

Various studies gave conflicting results, as is typical in medical science. Some showed that PPI medicines had no effect on Plavix efficacy and others suggested that a true interaction might be present. Of course, some data that supported that PPIs weaken Plavix were from ‘test tube’ experiments, and not in studies with real patients. Beware the danger of the surrogate endpoint!

At first, this was causing consternation for PPI-loving gastroenterologists and Plavix-pushing cardiologists. Who would prevail in this conflict?

  • The endoscopers?
  • The cardiac catheterizers?
  • The plaintiffs’ lawyers?
It was nearly impossible to peruse a medical journal that was not reprocessing this issue. Search this subject on the internet, and then take a month off so you can read through all the hits. Of course, after reading the first half dozen, you will then be reading reruns.

While I now offer speculation, which is not data, I doubt that combining these drugs, as is done thousands of times every day, will harm patients. I expect in the next year or so to read medical studies that will argue that the PPI-Plavix combo meal will not lead to doomsday, and that the initial reports were hyped. The FDA, despite the weak evidence, has issued a warning regarding prescribing Plavix and Prilosec (omeprazole) together. These government caveats are like tattoos; they are easier to affix than they are to remove.

We have read about other PPI risks over past years. They are associated with pneumonia, C. difficile colitis, vitamin B12 deficiency and hip fractures. Once again, the FDA issued a warning regarding PPI and associated bone fractures, despite the absence of persuasive medical evidence that these drugs can actually break bones.

As journalists know, ‘if it bleeds it leads’. Well, we gastroenterologists know that Plavix causes plenty of bleeding. I guess that’s why it became front page news.


  1. I wish I would have wrote this piece.
    Great insight.
    Thank you.

  2. Ed, considering your comment, I hope you will visit the blog often! Thanks for the kind words.

  3. This post raises a lot of interesting questions which I hope you will address in future posts.

    I'm seeing increasing numbers of new referrals of patients who tell me right up front that they will not take PPIs under any circumstances, and that it is my responibility to be well-versed in all the homeopathic and folk remedies.

    I usually mutter that if they want more information along those lines they can google it themselves. I have been known to pass along, to patients who have mild GERD symptoms and normal endoscopies, the old folk remedy of dilute apple cidar vinegar. People swear by it. Perhaps it has some sort of counterirritant effect. Who knows.

    I predict that we will see a rise in heretofore obsolete gastric resections and ulcer-related deaths.

    I'd be interested in your take on the matter.

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  5. @A. Bailey, vinegar? Interesting concept. Need more specifics. Balsamic? White? Cider?

    Yeah, I have lots of patients who consult with Dr. Google before seeing me. Haven't you consulted this same doctor at times for a second opinion?

  6. I'm closely following you, Informations which you shared very enlightening.I hope you will continue in this way. I'll continue to follow you.


  7. Thanks! The combination of Plavix and PPi medicines is a burning matter, which is being treated very light headed by most organizations. it's about time we put this in our top priorities. Thanks again.

  8. Plavix has done wonders for me. I've tried other anti-clotting medicines; Plavix has provided a better quality of life for me.

  9. Thank you for this post. I think you are correct about this. Fear is a much more potent motivator for many a patient (and the media) than is scientific analysis.

    I have recently published a review article about this very issue in the January 2011 issue of the Cleveland Clinic Journal of Medicine ( In the article I propose an algorithm that could help physicians rationally decide on the appropriateness of PPI therapy in a patient who requires Plavix. I hope that ACP members find the algorithm useful for their patients.