Long-Term Acid Inhibition: Benefits and Harms

Abstract

Proton pump inhibitors (PPIs) are the drugs of choice in the therapy of acid-related disorders. PPIs are as a class remarkably safe. Serious adverse events such as acute interstitial nephritis are extremely rare. Some reports in recent years have placed some concern on the long-term use of PPIs. Long-term therapy with PPIs can cause hypochlorhydria, hypergastrinemia and has interactions on hepatic cytochrome P450 enzymes which might increase the risk of infectious complications, nutritional deficiencies and drug-drug interactions. The vast majority of data came from retrospective case-control or cohort studies which are prone to confounders. At the moment we cannot conclude that long-term PPI use causes anemia, osteoporosis and bone fractures, increases the risk for pulmonary or enteric infections, has an effect on GUT mucosa, polyp or tumor formation, or that PPI use increases the risk of cardiovascular events in patients on PPIs and clopidogrel. We need prospective randomized trials to be able to definitely answer the questions raised in epidemiologic studies. Maintenance therapy with PPIs should be started only if strict indications for that therapy are fulfilled.

Potent acid inhibition by vonoprazan in comparison with esomeprazole, with reference to CYP2C19 genotype

“…In rats, hypergastrinaemia on long‐term administration of a PPI was associated with the hyperplasia of ECL cells and carcinoid . These findings raised concerns about the possibility of the same association with PPI‐induced hypergastrinaemia and gastric carcinoid in humans, but this association has not been proved in humans . Although a few case reports on gastric carcinoid and gastric neuroendocrine carcinoma with long‐term PPI treatment have appeared, these reports did not provide evidence for a causal relationship between long‐term PPI treatment and neuroendocrine tumours.…”

“…[50][51][52][53][54] These findings raised concerns about the possibility of the same association with PPIinduced hypergastrinaemia and gastric carcinoid in humans, but this association has not been proved in humans. [55][56][57][58][59] Although a few case reports on gastric carcinoid and gastric neuroendocrine carcinoma with long-term PPI treatment have appeared, 60-62 these reports did not provide evidence for a causal relationship between long-term PPI treatment and neuroendocrine tumours. Rodents treated with vonoprazan in pre-clinical toxicity testing for 2 years at a dosage equivalent to 20 mg daily in humans developed hyperplasia of ECL cells and gastric carcinoid.…”

Systematic review: the effects of long‐term proton pump inhibitor use on serum gastrin levels and gastric histology

“…These findings raised the possibility of a relationship between PPI-induced hypergastrinaemia and the development of proliferative ECL cell lesions and NETs in humans. [29][30][31][32] These concerns were reiterated in recent case reports that presented evidence on the potential risks of NET development during long-term PPI therapy. [33][34][35][36] A key modulatory factor in the development of hypergastrinaemia is infection with Helicobacter pylori.…”

“…In female rats, hypergastrinaemia resulting from lifelong administration of high doses of PPIs or H 2 receptor antagonists, or from partial gastric corpectomy was associated with the development of ECL cell hyperplasia and neuroendocrine tumours (NETs). These findings raised the possibility of a relationship between PPI‐induced hypergastrinaemia and the development of proliferative ECL cell lesions and NETs in humans . These concerns were reiterated in recent case reports that presented evidence on the potential risks of NET development during long‐term PPI therapy …”

Esomeprazole use is independently associated with significant reduction of BMD: 1-year prospective comparative safety study of four proton pump inhibitors

“…According to a recently published analysis of drug consumption in Kosovo for three referring years (2011)(2012)(2013), there was a trend of increased PPI expense in each subsequent year, reaching a total of € 3,723,287.56 [12]. For most indications, PPIs are used only in the short term (4-8 weeks), with the exception of severe GERD and as concomitant therapy for prevention of NSAID-induced gastrointestinal damage, where they can be used as maintenance therapy for extended periods of time [13]. PPI are recognized as superior to histamine H 2 receptor antagonists in preventing the occurrence of NSAID-induced gastrointestinal lesions, and their use is generally an agreed option to enable patients to continue to use NSAIDs [14][15][16][17].…”