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.