|Minnesota Pharmacist Journal - Winter 2018|
Proton Pump Inhibitors: Know When Short or Long Term Use Is Appropriate
By Brittany Thelemann, PharmD, New Ulm Medical Center
Background: Proton Pump Inhibitors (PPIs) are a common class of medications used to treat gastrointestinal (GI) conditions associated with acid production. In recent months, there has been a focus on inappropriate uses and durations of PPIs. In one U.S. study, only 39% of inpatients’ prescriptions were compliant to guidelines. Not only are PPIs being overused, but they also carry risks for potential adverse effects. Clinical guidelines suggest PPIs may be associated with chronic kidney disease, fractures, C. diff, pneumonia, micronutrient deficiencies and dementia. These risks may result from not only long-term use of PPIs, but short-term use as well.
Evidence: Expert guidance is now available for duration of PPI therapy. Based on the results of Khan et al., guidelines recommend a treatment duration of eight weeks with standard (once daily) dose PPIs for gastroesophageal reflux disease (GERD). The study found that 80% of patients experienced healing of reflux esophagitis and symptom relief during the eight-week duration. Appropriate lifestyle modifications for patients experiencing GERD symptoms is also an important consideration during therapy. Other appropriate indications requiring short term treatment include duodenal ulcers, gastric ulcers, and H. pylori. Lastly, patients in the ICU with risk factors should be given a PPI during their hospital stay for stress ulcer prophylaxis but discontinued upon discharge. Three large meta-analyses found that the risk of bleeding in the ICU is reduced by about 60% in patients receiving stress ulcer prophylaxis compared with those treated with placebo or no prophylaxis.
“Recent headlines related to proton pump inhibitors (PPIs) have included inappropriate usage and potential adverse effects. Some conditions require long term PPI therapy, but in most cases a short duration is more appropriate.”
While short-term therapy is preferred, there are a few instances that require longer treatment durations. Long-term PPI therapy is appropriate for prevention of NSAID-induced ulcers in high risk patients. The available evidence is strong, with consistent ulcer reductions of 50% in large RCTs, meta-analyses of RCTs and large observational studies in clinical practice. Patients on chronic anticoagulation at increased risk of a GI bleed (age>65, concomitant use of corticosteroids and/or previous history of GI bleed) may also benefit from long-term PPI therapy. While gastroprotection is generally not advised unless a concomitant antiplatelet or NSAID therapy is prescribed, a very recent retrospective cohort study by Ray et al. found that PPI co-therapy is associated with reduced risk of warfarin-related upper GI bleeding. Other indications requiring long-term therapy include Barrett’s esophagus, Zollinger-Ellison Syndrome, eosinophilic esophagitis and complicated/refractory GERD.
Discussion: Proton Pump Inhibitors hold strong evidence for efficacy which has led to their unfortunate overuse. It is important that providers balance risks and benefits of long-term PPIs. Despite the long list of potential adverse effects associated with PPI therapy, the quality of evidence for most of those risks has been consistently low because of studies’ conflicting results. While PPIs are effective, there are other therapies available to manage GI conditions. Inadomi et al. found that 33% of patients with uncomplicated GERD on PPI therapy were able to successfully transition to an H2 antagonist while another 16% were transitioned off acid suppression completely. In patients who fail or cannot be transitioned, providers should periodically reevaluate patients on long-term PPIs to ensure patients are on the lowest dose sufficient to manage symptoms.
Clinical Impact: When PPIs are appropriately prescribed, their benefits are likely to outweigh their risks. However, combating inappropriate long-term use of PPIs is crucial. For example, PPIs used in the hospital to prevent stress ulcers should be stopped upon discharge. Additionally, H2RAs or antacids may be suggested to manage acid reflux symptoms instead of jumping to a PPI. If long-term treatment is necessary, consider benefits of continuous, intermittent or on-demand therapy. Lastly, if the decision is made to stop PPI therapy, suggest a taper over a few weeks to prevent acid rebound. First, reduce the dose (if not at the minimum dose per day). Then, extend the dosing interval to every other day and possibly every third day.
Freedberg DE, Kim LS, Yang YX. The risks and benefits of long-term use of proton pump inhibitors: expert review and best practice advice from the American Gastroenterological Association. Gastroenterology. 2017;152(4):706-715. doi: 10.1053/j.gastro.2017.01.031.
Scarpignato C, Gatta L, Zullo A, et al. Effective and safe proton pump inhibitor therapy in acid-related diseases - a position paper addressing benefits and potential harms of acid suppression. BMC Med 2016;14:179. doi: 10.1186/s12916-016-0718-z.
Khan M, Santana J, Donnellan C, Preston C, Moayyedi P. Medical treatments in the short term management of reflux oesophagitis. Cochrane Database Syst Rev. 2007;2. doi: 10.1002/14651858.CD003244.pub2.
Ray WA, Chung CP, Murray KT, et al. Association of proton pump inhibitors with reduced risk of warfarin-related serious upper gastrointestinal bleeding. Gastroenterology. 2016;151(6):1105-1112.e10. doi: 10.1053/j.gastro.2016.08.054.
Inadomi JM, Jamal R, Murata GH, et al. Step-down management of gastroesophageal reflux disease. Gastroenterology. 2001;121:1095–1100. doi: 10.1053/gast.2001.28649.