PPI Wars Part 2
by Kenneth R. DeVault, MD, FACG
One of my first duties as a member of the College was writing the initial ACG gastroesophageal reflux disease (GERD) guidelines in 1995 (1). This document was produced during the early years of omeprazole’s availability. The early safety concerns with proton pump inhibitors (PPI) were dismissed and several other proton pump inhibitors were subsequently introduced with various claims of superiority setting off the first of the PPI Wars (company versus company).
The biggest admitted downside of PPI therapy at that time was cost. With the advent of over-the-counter and generic PPI, cost took a back seat and many more patients were managed on chronic, long-term PPI with no real attempt to stop or decrease that therapy.
Over the past several years, a number of potential adverse effects of PPI therapy have been suggested by large, observational studies.
- Decreased calcium absorption and increased risk of fracture
- Increased risk of Clostridium difficile infection
- Increased risk of community and hospital acquired pneumonia and other infections
- Drug interactions, most importantly to clopidogrel (Plavix)
- Decline in vitamin B12 stores
- Decline in serum magnesium
- Increased risk of chronic kidney disease (CKD)
- Increased risk of dementia
The first four of these were addressed in the most recent 2013 update of ACG’s GERD guidelines (2). The authors felt that hip fractures and osteoporosis should only be a concern in those with other risk factors, admitted that PPI might increase the risk of C. diff, and agreed that there was a very small increased risk of pneumonia on PPI. They did not feel the interaction with clopidogrel to be clinically significant.
In addition to the interactions addressed in the GERD guidelines, B12 and Mg are easy to deal with as long as you know of the interaction, but the two most recent associations (CKD and dementia) are more difficult. Both associations were found in large observational studies that cannot assign causality. While the authors used everything in their power to avoid conflicting factors, I cannot know with certainty that the PPI patients were not “sicker” than the controls independent of the PPI use. If the CKD association is real, we do not know if it is reversible or permanent. Dementia is even more difficult since we have no test, are not sure of the relationship, and have no real idea of why this might be the case.
I would suggest the following:
- Face up to the possibility that some of the associations may be true, both in your own thinking and interactions with patients.
- Know why the patient is on the medication. If they have Barrett’s, strictures or perhaps a history of LA-C or D esophagitis, they likely will need to stay on long-term PPI, regardless of symptoms. On the other hand, if they have symptoms and no mucosal damage, less aggressive acid blockade may be effective.
- Emphasize life-style changes, particularly diet and weight loss. GERD is a lifestyle illness for many patients.
- Practice step down therapy. Many (perhaps half) of patients on BID can be stepped down to one daily and many of those on once daily can have adequate symptom control on H2 blockers
- Make sure patients understand that fear of these rare complications is not a reason to choose reflux surgery. There may be other reasons, but the complications of surgery certainly are more common that these theoretical PPI complications.
- Watch the literature. There will most certainly be additional studies forthcoming, but I would not expect definitive answers to many of these questions in the near future.
I am sure there are many different thoughts and opinions on this issue. I would invite you to the GI Circle where we can have ongoing dialog and perhaps even debate.
- DeVault KR, Castell DO. Guidelines for the diagnosis and treatment of gastroesophageal reflux disease. Practice Parameters Committee of the American College of Gastroenterology Arch Intern Med. 1995 Nov 13; 155(20):2165-73
- Katz PO, Gerson LB, Vela MF. Diagnosis and Management of Gastroesophageal Reflux Disease Am J Gastroenterol 2013; 108:308–328