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Content Update

July 7, 2019

Updated Recommendation on the Long-Term Safety of Proton Pump Inhibitors (PPIs): In 2017, the American Gastroenterological Association (AGA) released best practice recommendations evaluating the risks and benefits of long-term proton pump inhibitor (PPI) therapy based on observational studies, including chronic kidney disease, dementia, bone fracture, myocardial infarction, Clostridioides difficile infection, other enteric infections, pneumonia, micronutrient deficiencies, and gastrointestinal cancer. This report stated that the risk of C. difficile infection was “modest” compared with traditional risk factors such as antibiotics. In the first and largest prospective, randomized trial examining the long-term safety of PPIs (specifically pantoprazole) published in 2019, after a median of three years of use, PPIs did not increase the risk of any of these adverse effects except for non-Clostridioides difficile enteric infections. The authors concluded that PPI therapy is safe for up to 3 years and that limiting prescription of PPI therapy because of concerns of long-term harm is not warranted.



Upon completion of the chapter, the reader will be able to:

  1. Recognize differences between ulcers induced by Helicobacter pylori, nonsteroidal anti-inflammatory drugs (NSAIDs), and stress-related mucosal damage (SRMD) in terms of risk factors, pathogenesis, signs and symptoms, clinical course, and prognosis.

  2. Identify desired therapeutic outcomes for patients with H. pylori–associated ulcers and NSAID-induced ulcers.

  3. Identify factors that guide selection of an H. pylori eradication regimen and improve adherence with these regimens.

  4. Determine the appropriate management for a patient taking a nonselective NSAID who is at high risk for ulcer-related gastrointestinal (GI) complications (eg, GI bleed) or who develops an ulcer.

  5. Employ an algorithm for evaluation and treatment of a patient with signs and symptoms suggestive of an H. pylori–associated or NSAID-induced ulcer.

  6. Given patient-specific information and the prescribed treatment regimen, formulate a monitoring plan for drug therapy either to eradicate H. pylori or to treat an active NSAID-induced ulcer or GI complication.


Peptic ulcer disease (PUD) refers to a defect in the gastric or duodenal mucosal wall that extends through the muscularis mucosa into the deeper layers of the submucosa.1 PUD is a significant cause of morbidity and is associated with substantial health care costs.2,3 Although there are many etiologies of PUD, the three most common are (a) H. pylori infection, (b) use of nonsteroidal anti-inflammatory drugs (NSAIDs), and (c) stress-related mucosal damage (SRMD).

Complications of PUD include gastrointestinal (GI) bleeding, perforation, and obstruction. Complications of untreated or undiagnosed H. pylori infection include gastric cancer and PUD. This chapter focuses mainly on pharmacotherapy of PUD related to H. pylori infection or NSAID use. Prophylaxis of SRMD in hospitalized patients is also discussed briefly.


PUD affects approximately 10% of ...

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