Estimates of all cause mortality and cause specific mortality associated with proton pump inhibitors among US veterans: cohort study

Xie, Yan; Bowe, Benjamin; Yan, Yan; Xian, Hong; Li, Tingting; Al‐Aly, Ziyad

doi:10.1136/bmj.l1580

Cited by 172 publications

(189 citation statements)

References 63 publications

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“…Recent studies suggested that prolonged PPI exposure was potentially associated with serious adverse effects, including chronic kidney diseases, cardiovascular diseases, or gastrointestinal malignancies, and with a small excess of causespecific mortality [33,34]. PPI therapy should be avoided if not necessary, and deprescribing should be considered whenever possible through regular reevaluation.…”

Section: Discussionmentioning

confidence: 99%

Use of proton pump inhibitors in adults in France: a nationwide drug utilization study

Lassalle

Tri

Bardou

et al. 2019

Eur J Clin Pharmacol

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Purpose Proton pump inhibitor (PPI) drugs are approved for the management of gastric acid-related diseases, mainly treatment of gastroesophageal reflux disease, treatment of nonsteroidal anti-inflammatory drugs (NSAID)-related gastrointestinal complications and prevention in at-risk patients, Helicobacter pylori eradication, and treatment of ulcers. PPIs are one of the most commonly prescribed drug class worldwide, and off-label use is widespread. The aim of this study was to describe outpatient PPI use of the whole adult population in France, based on the French National Health Data System (SNDS). Methods All individuals aged 18 years or older, with at least one dispensing for PPI between January 1, 2015 and December 31, 2015, were identified as PPI users. PPI users were considered as new users if they received no dispensing for PPI in the prior year. New users were followed until treatment discontinuation or up to 1 year, whichever occurred first. Characteristics of new users and of their PPI treatment were described, overall and separately by treatment indication. Results In total, 15,388,419 PPI users were identified in 2015 (57.0% women; mean age 57.0 years), accounting for 29.8% of the French adult population. Of them, 7,399,303 were new PPI users; mean treatment duration was 40.9 days, and 4.1% received a continuous PPI therapy lasting more than 6 months (10.2% among new users > 65 years versus 2.4% among those 18-65 years). For 53.5% of new users, indication for PPI therapy was a co-prescription with NSAID; in this indication, the large majority of patients (79.7%) had no measurable risk factor supporting a systematic prophylactic co-prescription of PPI. A proportion of 32.4% of new users did not have any identified comedication or inpatient diagnosis supporting an indication for PPI therapy; among them, only a small proportion (7.3% overall, and 8.4% of patients aged > 65 years) underwent a procedure investigating the digestive tract at the time of PPI initiation. Conclusion The results of this study suggest PPI overuse in France, not always in line with the French guidelines. In particular, inappropriate co-prescription with NSAID was frequent. Efforts should be made to limit PPI treatment to appropriate indications and durations.

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Section: Discussionmentioning

confidence: 99%

Use of proton pump inhibitors in adults in France: a nationwide drug utilization study

Lassalle

Tri

Bardou

et al. 2019

Eur J Clin Pharmacol

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“…Nevertheless, the list of potential side-effects related to long-term PPI use is increasing, including among others, chronic kidney disease, osteoporosis and fractures, Clostridium difficile infections, community acquired pneumonia, cardiac diseases, and even increased mortality [8][9][10][11][12][13][14][15][16][17][18][19]. An increasing number of studies have also investigated the risk of cancer with most evidence existing for gastric, colorectal and pancreatic cancer.…”

Section: Introductionmentioning

confidence: 99%

Long-term proton pump inhibitor usage and the association with pancreatic cancer in Sweden

2019

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Background The long-term safety of proton pump inhibitors (PPIs) is increasingly questioned. The aim of our study was to assess the risk of pancreatic cancer among longterm PPI users in Sweden. Methods This population-based nationwide Swedish cohort study including 796,492 adult long-term PPI users has been used to calculate the standardized incidence rate ratios (SIRs) and 95% confidence intervals (CI) for pancreatic cancer, stratifying by indications of use, age, sex, and duration of use. The risk among all 20,210 long-term H2-receptor antagonist users was assessed as comparison.Results Pancreatic cancer was found in 1733 long-term PPI users, and 25 H2-receptor antagonist users. For PPI users, the risk of pancreatic cancer was increased overall (SIRs = 2.22; 95% CI 2.12-2.32) and in all subgroup analyses, with the highest risk among PPI-users younger than 40 years (SIR = 8.90,, and among individuals with a history of Helicobacter pylori (SIR = 2.99, 95% CI 2.54-3.49). After the first year after enrolment (during which PPI use may be because of early symptoms of pancreatic cancer), the risk remained increased over time, with SIR = 1.57 (95% CI 1.38-1.76) after 5 years. No associations were found for H2-receptor antagonists (SIR = 1.02, 95% CI 0.66-1.51). Conclusions This large study showed an increased risk of pancreatic cancer in long-term users of PPIs in Sweden, in particular among the youngest users.

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“…Some of these adverse effects are associated with an increased risk of death 9 . Recently, some studies have shown an excessive risk of long‐term all‐cause mortality and cause‐specific mortality among patients using PPIs 9,10 . The potential mechanism may be that the decreased gastric acid secretion and alteration in gut bacterial flora could lead to an increased risk of infection and less absorption of nutrients 11 .…”

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confidence: 99%

Proton Pump Inhibitor Use Before ICU Admission Is Not Associated With Mortality of Critically Ill Patients

Shi

Zhang

2020

The Journal of Clinical Pharma

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Some studies have shown that the long‐term use of proton pump inhibitors (PPIs) is associated with many adverse events that may increase mortality; however, the relationship between premorbid PPI use and in‐hospital mortality has yet to be validated in critically ill patients. Therefore, we performed this study to determine whether the preadmission use of PPIs is associated with mortality in patients admitted to the intensive care unit. This was a retrospective study with a large and freely accessible database in critical‐care medicine (the Multiparameter Intelligent Monitoring in Intensive Care III project). The clinical data and outcomes of 17 473 patients, consisting of 1895 in the PPI group, 514 in the H2‐receptor antagonist group, and 15 064 control subjects, were collected during their hospital stay. The study outcome was in‐hospital mortality. A total of 17 473 patients were included in our study. PPI use was associated with significantly increased in‐hospital mortality in the original model without adjustment for any parameters (odds ratio 1.19; 95%CI 1.03‐1.38; P = .02). However, after adjustments had been made for age, sex, Elixhauser score, Simplified Acute Physiology Score, laboratory results, vasopressor use, ventilator use, and other parameters, PPIs were not associated with significantly increased in‐hospital mortality (odds ratio 1.04; 95%CI 0.87‐1.26; P = .614). In the subgroup analysis among patients with renal or liver disease, we still found that PPIs were not associated with a significant increase in in‐hospital mortality. We found no association between PPI use before ICU admission and increased in‐hospital mortality in critically ill patients compared with control subjects.

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Estimates of all cause mortality and cause specific mortality associated with proton pump inhibitors among US veterans: cohort study

Cited by 172 publications

References 63 publications

Use of proton pump inhibitors in adults in France: a nationwide drug utilization study

Use of proton pump inhibitors in adults in France: a nationwide drug utilization study

Long-term proton pump inhibitor usage and the association with pancreatic cancer in Sweden

Proton Pump Inhibitor Use Before ICU Admission Is Not Associated With Mortality of Critically Ill Patients

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