Safety and Complications of Long-Term Proton Pump Inhibitor Therapy: Getting Closer to the Truth

Corley, Douglas A.

doi:10.1053/j.gastro.2019.07.039

Cited by 33 publications

(25 citation statements)

References 16 publications

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“…Collectively, results of this meta-analysis support that PPI is associated with increased mortality in cirrhotic patients. Considering the potential overutilization of PPIs in patients with cirrhosis [5], as well as the potential safety consideration related to the long-term use of PPIs [3], decision for the prescription of PPIs in cirrhotic patients should only be made after carefully evaluating the appropriate indications and balancing the benefits and potential risk of adverse outcomes in these patients.…”

Section: Discussionmentioning

confidence: 99%

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Proton pump inhibitor use and mortality in patients with cirrhosis: a meta-analysis of cohort studies

Wu¹,

Zhang

Yu³

et al. 2020

Bioscience Reports

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Background: Proton pump inhibitor (PPI) is commonly used in patients with cirrhosis. However, some studies demonstrated that PPI use was associated with adverse outcome in patients with cirrhosis. We aimed to perform a meta-analysis of cohort studies to evaluate the association between PPI use and mortality in cirrhotic patients. Methods: Relevant studies were obtained via search of PubMed and Embase databases. A randomized-effect model was used to pool the results. Subgroup analyses were performed to evaluate the source of heterogeneity. Results: Overall, 21 cohort studies with 20,899 patients and 7457 death events were included. The pooled results with a randomized-effect model showed that PPI use was associated with significantly increased risk of mortality in patients with cirrhosis (adjusted relative risk [RR] = RR: 1.39, P<0.001) with considerable heterogeneity (I2=73%). Subgroup analyses showed that characteristics such as patient ethnicity, sample size, definition of PPI use, and complications of patients did not affect the association. However, the association between PPI use and mortality was independent of study characteristics including patient ethnicity, sample size, complications, definition of PPI use, and follow-up duration. However, the association between PPI use and mortality in cirrhotic patients was significant in retrospective studies (RR: 1.40, P<0.001), but not in prospective studies (RR: 1.34, P=0.33). Conclusions: PPI use may be associated with moderately increased mortality in cirrhotic patients. Although prospective cohort studies are needed to validate our findings, PPI should only prescribed to cirrhotic patients with indications for the treatment.

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Section: Discussionmentioning

confidence: 99%

“…Proton pump inhibitors (PPIs) are the first-line medications for the treatment of acid-related diseases, such as gastroesophageal reflux disease, peptic ulcer, and Zollinger-Ellison syndrome et al [1][2][3]. For patients with cirrhosis, PPIs are also commonly used.…”

Section: Introductionmentioning

confidence: 99%

Proton pump inhibitor use and mortality in patients with cirrhosis: a meta-analysis of cohort studies

Wu¹,

Zhang

Yu³

et al. 2020

Bioscience Reports

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“…In addition to the question of the long-term possibility of chronic hypergastrinemia-induced gastric carcinoids, in a number of other recent specific studies, as well as observational and epidemiological studies, other possible PPI-induced side-effects with potential long-term safety considerations are being reported, which are attributed to the PPI-induced chronic hypergastrinemia, hypoachlorhydria, to other mechanisms, or due to unknown mechanisms [2,3,7,8,9,11,13,14,15,16,38,44].…”

Section: Why Is Prolonged Ppi Use Receiving Increased Attention Anmentioning

confidence: 99%

“…This study [8] reported that the only possible PPI-induced safety difference detected [8] was an increased incidence of enteric infections in the PPI-treated patients. In an accompanying editorial [9], it was concluded from a review of this study that PPI treatment for appropriate indications can be safely continued for a few years with no increased risk for several reported potential side-effects except for a risk of gastrointestinal infections.…”

Section: Why Is Prolonged Ppi Use Receiving Increased Attention Anmentioning

confidence: 99%

“…PPIs are not only very widely used both for approved indications (peptic ulcer disease, gastroesophageal reflux disease (GERD), Helicobacter pylori eradication regimens, stress ulcer prevention), but are also one of the most frequently off-label used drugs (25–70% of total) [3], with the result that their use over the last decade has increased by >3 times in many countries and they are in the top 10 drugs prescribed [4,5,6]. PPIs have been increasingly used for >30 years, have proven effective, and in most reviews are considered safe [1,2,7,8,9]. However, there are currently a number of contentious issues related to their safety [2,3,7,10,11,12,13,14,15,16,17], primarily based on recent observational/epidemiological studies.…”

Section: Introductionmentioning

confidence: 99%

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Insights into Effects/Risks of Chronic Hypergastrinemia and Lifelong PPI Treatment in Man Based on Studies of Patients with Zollinger–Ellison Syndrome

Lee

Ramos-Álvarez

Ito

et al. 2019

IJMS

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The use of proton pump inhibitors (PPIs) over the last 30 years has rapidly increased both in the United States and worldwide. PPIs are not only very widely used both for approved indications (peptic ulcer disease, gastroesophageal reflux disease (GERD), Helicobacter pylori eradication regimens, stress ulcer prevention), but are also one of the most frequently off-label used drugs (25–70% of total). An increasing number of patients with moderate to advanced gastroesophageal reflux disease are remaining on PPI indefinitely. Whereas numerous studies show PPIs remain effective and safe, most of these studies are <5 years of duration and little data exist for >10 years of treatment. Recently, based primarily on observational/epidemiological studies, there have been an increasing number of reports raising issues about safety and side-effects with very long-term chronic treatment. Some of these safety issues are related to the possible long-term effects of chronic hypergastrinemia, which occurs in all patients taking chronic PPIs, others are related to the hypo-/achlorhydria that frequently occurs with chronic PPI treatment, and in others the mechanisms are unclear. These issues have raised considerable controversy in large part because of lack of long-term PPI treatment data (>10–20 years). Zollinger–Ellison syndrome (ZES) is caused by ectopic secretion of gastrin from a neuroendocrine tumor resulting in severe acid hypersecretion requiring life-long antisecretory treatment with PPIs, which are the drugs of choice. Because in <30% of patients with ZES, a long-term cure is not possible, these patients have life-long hypergastrinemia and require life-long treatment with PPIs. Therefore, ZES patients have been proposed as a good model of the long-term effects of hypergastrinemia in man as well as the effects/side-effects of very long-term PPI treatment. In this article, the insights from studies on ZES into these controversial issues with pertinence to chronic PPI use in non-ZES patients is reviewed, primarily concentrating on data from the prospective long-term studies of ZES patients at NIH.

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Proton pump inhibitors for the prevention of non-steroidal anti-inflammatory drug-induced ulcers and dyspepsia

Garegnani

Liquitay

Puga-Tejada

et al. 2022

Cochrane Database of Systematic Reviews

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Safety and Complications of Long-Term Proton Pump Inhibitor Therapy: Getting Closer to the Truth

Cited by 33 publications

References 16 publications

Proton pump inhibitor use and mortality in patients with cirrhosis: a meta-analysis of cohort studies

Proton pump inhibitor use and mortality in patients with cirrhosis: a meta-analysis of cohort studies

Insights into Effects/Risks of Chronic Hypergastrinemia and Lifelong PPI Treatment in Man Based on Studies of Patients with Zollinger–Ellison Syndrome

Proton pump inhibitors for the prevention of non-steroidal anti-inflammatory drug-induced ulcers and dyspepsia

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