The Perils of PPIs How can they harm us? What should they be used for?

Quiz: Which of the following is a result of chronic PPI use? –Increase in fractures –Increase in CAP –Increase in risk of C. difficile –All of the above

If you put all brands of PPIs together, they account for $13.9 billion in sales per year.

PPIs and Fracture PPIs decrease calcium absorption JAMA, 2006: nested case control study in a large (1.8 million) general practice data base in Great Britan. RR of hip fracture was 1.6 in those taking PPIs for more than 12 months. The risk increased with duration and dose. Women’s Health Initiative: PPI use conferred a modestly increased risk of spine, forearm, and wrist fractures. Other studies have confirmed these findings. H2 blockers may or may not increase risk of fracture.

PPIs and CAP Acid reduction may allow pathogens to colonize the upper GI tract JAMA, 2004: Case control study done in the Netherlands of adults on acid suppressive therapy. RR for CAP was 1.89 for patients on PPIs. Archives of Internal Medicine, 2007: Similar results in a Danish cohort. PPIs also significantly increase the risk of hospital acquired pneumonia. H2 blockers may have the same effect.

PPIs and C. difficile Gastric acid lowers the risk of infection. Studies looking at both in-patients and people living in the community have demonstrated increased rates of C. difficile in patients taking PPIs. (Also H2 blockers, though less so.) RR ranges from 2.1 to 3.5. Again, the higher the dose the higher the risk. The use of PPIs during treatment for C. difficile almost doubles the risk of recurrence.

How should PPIs be used? For indicated therapies only: Peptic ulcer disease, eradication of H. pylori, NSAID induced ulcers, Zollinger-Ellison syndrome, severe GERD. Avoid long term use. Avoid supra-therapeutic doses.

How to deal with withdrawal.

Treat underlying disorders Taper Replace with H2 blockers Use non-pharmacologic therapies Modify behavior