COMMENTARY from Article on Medscape Gastroenterology

When It Comes to PPIs, Why All the 'Mayhem'?
David A. Johnson, MD
Disclosures at end

May 26, 2017

Hello. I am Dr David Johnson, professor of medicine and chief of gastroenterology at Eastern Virginia Medical School in Norfolk, Virginia.

It would be an understatement to say that proton pump inhibitor (PPI) noise has created mayhem for patients and healthcare providers. Two papers have just come out that will help us put some sanity around these concerns. The first paper is an evidence-based Delphi international consensus[1] that addressed over-the-counter (OTC) use of PPIs, and the second is the most recent expert consensus from the American Gastroenterological Association (AGA)[2] for prescription use of PPIs. These papers give very strong re-edification that evidence of harm is very weak.

Let's go through the different concerns and talk about best practice recommendations.
Dementia Risk

The AGA[2] recognizes that the science on the [association of dementia with PPI use] is lacking. For the two studies that alleged harm, the odds ratios (ORs) were extremely low, [and the studies were] very subject to stratification bias. There was no recommendation for concern.
Bone Fracture Risk

The very insidious concern about bone fracture [risk associated with PPIs] goes back to a University of Pennsylvania study published in JAMA.[3] Long-term, evidence-based studies, such as that from Laura Targownik[4] in Canada, have shown us that there is not a concern for bone density loss. For both the Delphi consensus[1] and the AGA[2] documents, there is no specific recommendation that people on OTC or long-term PPIs should be monitored any differently for bone density. Patients do not need baseline or serial sequential studies, and they do not need supplemental calcium.
Vitamin and Mineral Changes

Along those same lines, [possible changes] in iron and magnesium [levels associated with PPI use] are recognized in the literature. These changes may be idiosyncratic and rare. Both the Delphi consensus[1] and the AGA expert guidance[2] do not recommend routine monitoring of any element, including calcium, magnesium, and iron. In addition, vitamins, such as B12, do not need to be monitored in people on long-term or short-term PPIs.
Renal Insufficiency

How about renal insufficiency?

The renal issue has made a lot of noise, and people are fearful about acute or chronic renal insufficiency. Both the Delphi and the AGA documents recognize that there is a risk for renal insufficiency due to acute interstitial nephritis. We think that this is idiopathic. Both documents recommend that people do not need to be monitored or screened routinely for renal toxicity [associated with PPI use]. Only symptom-directed testing, if applicable, is recommended.
Infection Risk

How about infection?
There are randomized controlled trial (RCT) data finding that pneumonia is not increased with PPIs and actually may be a little bit decreased.

The bigger concern has been for infection with Clostridium difficile. The ORs are very low, in the 1.5 to 1.6 range, and there are stratification biases across the C difficile study populations. [For patients on PPIs,] we are talking about relatively nominal acid suppression rather than true achlorhydria, which you would see in a vagotomy patient or gastric surgery patient. The consensus in the Delphi document[1] does not recommend that PPIs be stopped in concern for C difficile. The researchers also recommend that there is no rationale for probiotic use in patients on PPIs. Other types of infection have been of concern.

One that is a bit contrarian is spontaneous bacterial peritonitis (SBP). There are nominal ORs in the population of patients with cirrhosis with ascites [for this infection risk]. Whether or not this is going to bear out, the recommendation is that if you need a PPI, you should take it; and if you do not, you should not. Routine monitoring or avoidance of a PPI in a patient with cirrhosis specifically because of SBP concern is not recommended at this point. These patients have lots of other complexities that may put them at risk for SBP.
Interaction With Clopidogrel

Another area of concern is the interaction with Plavix