Primary Care Corner with Geoffrey Modest MD: PPI Harms and Benefits

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By Dr. Geoffrey Modest

There was a useful editorial detailing the indications for long-term proton-pump inhibitor use (see Laine L. Am J Gastroenterol 2016; 111:913). As many of you know from prior blogs, I have been very concerned that many patients are on long-term PPIs because: they work; when patients are doing better on them, we can move on to address other issues; changing them involves somewhat detailed/time-consuming discussions with patients (detracting from focusing on the other issues); changing them may not work, so we might be back to square-one; when patients see GI specialists, they are uniformly put on PPIs (at least in my experience); and, despite GI specialty recommendations to step-down therapy from PPIs to H2-blockers or antacids, studies show that this rarely happens. This review focuses on the indications for long-term PPIs, with little attention to the harms, but my guess is that most patients on long-term PPIs do not qualify for them even by these recommended indications: there are some studies finding that 70-80% of hospitalized patients put on PPIs do not have an appropriate indication. Details of the editorial:

  • The caveat: most of the studies were intervention studies with retrospective observational analysis (i.e., they were not set up as large studies comparing different therapies, and following the patients for many years to assess long-term effectiveness or adverse events)
  • GERD: for GERD symptoms, most patients do well with on-demand therapy.  In general, advice is given for long-term PPIs if erosive esophagitis, and there are studies suggesting that there is a higher risk of recurrent erosion when patients are put on placebo, H2-blockers, or intermittent PPIs. BUT, there are no data that show that recurrent esophageal erosions are harmful or that not using daily PPIs leads to Barrrett’s, and the risk of strictures is really low. Of note, many patients do use PPIs intermittently for symptoms, no matter what clinicians suggest, and most do fine, and there are observational data finding benefit of intermittent 2-4 week courses of daily therapy if twice-weekly heartburn recurs. But, I certainly do have patients who continue with their daily PPIs even if not necessary… the FDA guidelines suggest 4-8 weeks of PPIs for GERD. The editorialists in this review suggest that patients taking PPIs for GERD stop therapy 2 weeks after symptom resolution, and use H2-blockers or antacids as needed for infrequent symptoms, and if necessary, intermittent PPI courses of 2-4 weeks when symptoms recur >= 2x/week. [Given that it is often hard to do step-down therapy for GERD symptoms, I usually start with H2-blockers, step up to PPIs if necessary, and then try to step-down. In patients with mild symptoms, antacids often work just fine]
  • Barrett’s: basically, observational studies suggest PPIs may decrease neoplastic progression of Barrett’s, but the Am College of Gastroenterology and Am Gastroenterological Assn guidelines are more cautious: stating that long-term PPIs should be “considered” or discussed carefully with patients. And absolute risk of Barrett’s progression to adenocarcinoma is low (0.1%/yr). No FDA approval for this indication. The editorialists prefer using daily PPIs only if necessary to control GERD symptoms.
  • NSAIDs (my other nemesis, in terms of overuse and a plethora of adverse effects: GI, cardiovasc, renal, etc): PPIs (or misoprostol) do seem to decrease GI bleeding in those at high risk of bleeding (>65yo, high-dose NSAIDs, prior ulcers, or concurrent steroids/anti-thrombotics), and is supported in RCTs. These editorialists feel this is a clear indication for PPIs, though FDA approval is for durations up to 3-6 months. [My approach overall is to avoid long-term or high-dose NSAIDs, preferring topical treatments such as local injections, capsaicin, lidocaine gel, diclofenac gel, or oral acetaminophen. And I do have very few patients who take NSAIDs other than very intermittently]
  • Aspirin/anti-platelet agents: guidelines recommend PPIs in those at increased risk of bleeding (history of ulcers, concomitant anti-thrombotics, age>60 plus steroid therapy). Endoscopic ulcerations and recurrent ulcer bleeding have been documented in RCTs. No FDA recommendation [I do have lots of patients on low dose aspirin for cardiovascular and colorectal cancer prevention. There are some studies suggesting that low dose enteric-coated aspirin is erratically absorbed, and that the non-enteric coated aspirin has no greater incidence of gastric ulcers, so that is the one I use routinely. And with really minimal GI distress. So I do not prescribe any gastric protection routinely]
  • Dyspepsia: PPI therapy if <55yo with uninvestigated dyspepsia who are H pylori negative, or if H pylori prevalence is <10%. RCTs suggest PPIs are more effective than H2-blockers or antacids, with NNT=5. No clear guidelines on this. I did look up the Am Gastro Assn guidelines and there were no clear therapies suggested (see http://gi.org/guideline/management-of-dyspepsia/ ). The editorialists suggest intermittent PPIs if effective to control symptoms [again, I have had considerable luck with H2-blockers or antacids, so I do try them first]

Commentary:

  • This editorial reviews the accepted recommendations for using PPIs, along with some of the available data. I think it is useful because so many of the patients we see in the community are on long-term PPIs for non-recommended indications.
  • And, there are substantial data in the literature on the potential adverse effects of PPIs, including the potential for gastric atrophy (a potentially premalignant lesion) especially in those with concurrent H Pylori infections, decreased mineral absorption (iron, calcium, magnesium), decreased vitamin B12, decreased bone mineral density and increased fractures, hypomagnesemia, increased enteric infections (C. difficile, C jejuni), increased pneumonia, and increased cardiovascular events. There have been more recent associations with chronic kidney disease and dementia (see blogs below).
  • And, in case you are interested, not so surprisinglyPPIs adversely affect the microbiome (after all, the acidity of the stomach probably does have some evolutionary protective effect on preventing enteric infections (and maybe much much more). see doi:10.1136/gutjnl-2015-310376 .
  • Of course, there are some patients who really do need PPIs for symptom relief/quality-of-life, but these can often be used intermittently.
  • So, I initially prescribe PPIs only in patients who have really severe presenting symptoms of GI distress (though I will often get a stool for H Pylori antigen prior to starting the PPIs). And in those already on PPIs I personally have had good success in switching people to H2-blockers, or even just intermittent antacids, though some do seem to need an occasional PPI, rarely daily long-term PPIs.

Prior blog on Barrett’s:

Relevant prior blogs on adverse effects of PPIs:

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