Proton pump inhibitors (PPIs) are recommended as a first-line treatment for gastroesophageal reflux disease (GERD) and other acid related disorders. In recent years, concerns have been raised about the increasing prevalence of patients on long-term PPI therapy and inappropriate PPI use. It is well known that short-term PPI therapy is generally well tolerated and safe; however, their extensive long-term use is a major global issue. One of these long-standing concerns is PPI-induced gastrin elevation secondary to hypoacidity. Hypergastrinemia is believed to play a role in rebound hyperacidity when PPIs are discontinued resulting in induced dyspeptic symptoms that might result in the reinstitution of therapy. Gastrin exerts tropic effects in the stomach, especially on enterochromaffin-like (ECL) cells, and concerns have also been raised regarding the potential progression to dysplasia or tumor formation following long-term therapy. It is well known that a substantial number of patients on long-term PPI therapy can discontinue PPIs without recurrence of symptoms in deprescribing trials. What is unknown is how sustainable deprescribing should be undertaken in practice and how effective it is in terms of reducing long-term outcomes like adverse drug events, morbidity and mortality. Moreover, there is no clear consensus on when and how deprescribing strategies should be attempted in practice. This review sought to summarize the harms and benefits of long-term PPI therapy with special focus on gastrin elevation and its relation to deprescribing studies and future interventions that may improve PPI use.
Goals: The goal of this study was to elucidate the most important predictors for elevation of gastrin in patients on long-term PPI therapy through analysis of data from 2 published studies in Icelandic patients with erosive GERD. Background: Gastrin elevation is a known but variable consequence of proton pump inhibitor (PPI) therapy. Concerns have been raised about the clinical importance of chronic PPI induced gastrin elevation. Study: This cross-sectional analysis included patients with endoscopically verified erosive esophagitis receiving long-term PPI therapy. PPI exposure in dosage over weight (mg/kg) and dosage over body surface area (mg/m2) was compared with fasting gastrin levels in two separate multiple linear regression models. Data was collected on age, gender, weight, H. pylori infection, smoking, PPI duration and type. Results: Overall data from 157 patients (78 females) were analyzed. Median serum gastrin levels were higher in females than males (92 vs. 60 pg/mL; P=0.001). Simple linear regression showed a correlation between serum gastrin levels and gender (P=0.0008) as well as PPI exposure in mg/kg (P=0.0001) and mg/m2 (P=0.0001). Multiple linear regression analysis showed that PPI exposure, both in mg/kg (β=0.95 [CI=0.4-1.5]; P=0.001) and mg/m2 (β=0.02 [CI=0.0-0.0]; P=0.0015) along with female gender (β=0.2 [CI=0.0-0.4]; P=0.02) predicted higher gastrin values. Conclusions: Dosage and female gender seem to play an important role in the development of gastrin elevation on PPI therapy. A significant correlation was found between fasting serum gastrin and dosage of PPIs over weight and body surface area.
Female patients on long-term PPI therapy were 3 times more likely to tolerate half of their prior dose. Female gender had higher probability for successful step-down. These results indicate that women with gastroesophageal reflux disease might manage with lower doses of PPIs as compared with men.European Clinical Trial Database (https://eudract.ema.europa.eu/), number 2013-002067-26.
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