Ppi medicine
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Proton Pump Inhibitors (PPIs): Usage, Risks, and De-Prescribing Strategies
Introduction to Proton Pump Inhibitors (PPIs)
Proton pump inhibitors (PPIs) are among the most commonly prescribed medications globally, primarily used to treat acid-mediated upper gastrointestinal conditions such as gastroesophageal reflux disease (GERD) and peptic ulcers1 2. Despite their effectiveness, the widespread use of PPIs has raised concerns about overprescription and associated adverse effects1 2 3.
Overprescription and Economic Impact
The overprescription of PPIs is a significant issue, contributing to increased healthcare costs and polypharmacy1 4. Studies have shown that a substantial proportion of PPI prescriptions are not aligned with appropriate clinical indications, leading to unnecessary medication use4 10. This overuse is often driven by the prevention of gastro-duodenal ulcers in low-risk patients, stress ulcer prophylaxis in non-intensive care units, and the overtreatment of functional dyspepsia10.
Adverse Effects of Long-Term PPI Use
While PPIs are generally safe for short-term use, long-term use has been linked to several adverse health outcomes. Observational studies have associated PPI use with an increased risk of chronic kidney disease, fractures, vitamin B12 deficiency, and gastric pre-malignant lesions2 6 8. Additionally, there is evidence suggesting that long-term PPI use may lead to enterochromaffin-like (ECL) cell hyperplasia, although the clinical significance of this finding remains uncertain6.
De-Prescribing Strategies for PPIs
Given the potential risks associated with long-term PPI use, de-prescribing strategies are essential to minimize unnecessary medication use and reduce adverse effects. The American Gastroenterological Association (AGA) has provided Best Practice Advice (BPA) for de-prescribing PPIs in ambulatory patients1. Key recommendations include:
- Regular Review of PPI Indications: Primary care providers should regularly review the ongoing indications for PPI use and document these indications1.
- Trial of De-Prescribing: Patients without a definitive indication for chronic PPI use should be considered for a trial of de-prescribing1.
- Step-Down Therapy: For patients with an indication for chronic PPI use, step-down therapy from twice-daily to once-daily dosing should be considered1.
- Assessment of Gastrointestinal Bleeding Risk: Before de-prescribing, patients should be assessed for upper gastrointestinal bleeding risk using an evidence-based strategy1.
- Management of Rebound Symptoms: Patients discontinuing long-term PPI therapy should be advised about the possibility of transient upper gastrointestinal symptoms due to rebound acid hypersecretion1.
Pharmacogenetics and Precision Medicine
The variability in patient response to PPI therapy can be partly attributed to genetic differences, particularly in the CYP2C19 gene, which affects PPI metabolism7. Understanding these genetic differences can help tailor PPI therapy to individual patients, potentially improving clinical outcomes and minimizing adverse effects7.
Conclusion
PPIs are highly effective for treating acid-related disorders, but their overuse and associated risks necessitate careful consideration of their indications and the implementation of de-prescribing strategies. Regular review of PPI use, appropriate patient selection for de-prescribing, and consideration of genetic factors can help optimize PPI therapy and reduce unnecessary medication use.
Sources and full results
Most relevant research papers on this topic
AGA Clinical Practice Update on De-Prescribing of Proton Pump Inhibitors: Expert Review.
De-prescribing PPIs is a cost-effective strategy to lower pill burden and reduce risks, but should be considered for patients with uncertain benefits and those with known complications.
Systematic Review
Highly CitedAdverse Effects Associated With Proton Pump Inhibitors.
Proton pump inhibitors (PPIs) are associated with a number of adverse effects and are overprescribed, including chronic kidney disease.
Systematic Review
Rigorous JournalHighly CitedDiscontinuing Long-Term PPI Therapy: Why, With Whom, and How?
Long-term PPI use may be linked to adverse health outcomes, and strategies for reducing or stopping therapy can help maintain symptom control and reduce the risk of upper GI disease recurrence.
Literature ReviewAppropriateness of Proton Pump Inhibitor (PPI) prescription in patients admitted to hospital: Attitudes of general practitioners and hospital physicians in Italy.
Hospital clinicians rarely reconsider GP's choice to prescribe PPI, and assessing gastrointestinal risk and short-term re-evaluation of PPI prescriptions after discharge could improve PPI appropriateness.
Observational StudySmall molecules, big targets: drug discovery faces the protein–protein interaction challenge
Protein-protein interactions can be targeted for drug discovery, with successful inhibitors reaching clinical development for certain classes.
Highly CitedLong-term proton pump inhibitor (PPI) use and the development of gastric pre-malignant lesions.
Long-term PPI use may not significantly increase the risk of developing gastric pre-malignant lesions, but long-term use may not be recommended for certain diseases.
Meta-Analysis
Very Rigorous JournalHighly CitedProton pump inhibitors: from CYP2C19 pharmacogenetics to precision medicine
CYP2C19 genotype-guided dosing of proton pump inhibitors may improve clinical outcomes and minimize side effects, but its widespread implementation requires more data and research.
Highly CitedThe Indications, Applications, and Risks of Proton Pump Inhibitors.
Proton pump inhibitors are effective for treating gastric acid-related diseases, but their cost and potential adverse effects require only valid prescriptions for scientifically validated indications.
Systematic ReviewHighly CitedAbstract PD13-10: PD13-10 Impact of Proton Pump Inhibitors (PPI) on Palbociclib (PAL) Outcomes in Hormone Receptor-Positive, HER2-Negative Advanced Breast Cancer (HR+/HER2- ABC): Exploratory Analysis of the PARSIFAL Trial
PPI use during PAL-based regimens in HR+/HER2- advanced breast cancer patients may shorten progression-free survival, but overall survival and safety remain unchanged.
RCTThe appropriate use of proton pump inhibitors (PPIs): Need for a reappraisal.
The inappropriate use of proton pump inhibitors (PPIs) has increased costs and risks, necessitating educational initiatives to guide physicians and specialists to their correct use in clinical practice.
Highly Cited