Long-term Use Of Proton Pump Inhibitors Research Articles

Association between proton pump inhibitors and the risk of hepatocellular carcinoma.

Proton pump inhibitor (PPI) use has been reported to be associated with liver damage and might possibly be carcinogenic. We examined whether long-term PPI use increases the risk of hepatocellular carcinoma (HCC) in patients without viral hepatitis B or C. We conducted a nested case-control study in a cohort of patients without viral hepatitis in Taiwan from 2000 to 2013. In total, 29473 HCC cases and 294508 matched controls were included. Moreover, we identified prescriptions for PPI and durations between the PPI index date and cancer diagnosis date (or the corresponding date in controls). The adjusted odds ratio (AOR) for HCC associated with PPI use was 2.86 (95% confidence interval [CI], 2.69-3.04). Considering the use of PPIs determined according to cumulative defined daily dose (cDDD) subgroups, a dose-response effect was observed in patients exposed to 29-180, 181-240, 241-300, and 300+ cDDDs of PPIs. The AORs were 2.74 (95% CI, 2.57-2.93), 2.98 (95% CI, 2.50-3.56), 3.23 (95% CI, 2.59-4.02), and 3.43 (95% CI, 2.94-4.00) in the 29-180, 181-240, 241-300, and 300+ cDDD groups, respectively, compared with the 0-28 cDDD group. A sensitivity analysis revealed a consistent association between PPI use and the risk of HCC in subpopulations stratified by risk factors associated with HCC. This observational study demonstrated that PPIs might increase the risk of HCC.

Long-term proton pump inhibitor use does not raise hip fracture risk

Proton pump inhibitors (PPIs) reduce the production of stomach acid and are effective drugs for gastro-oesophageal reflux disease that are commonly prescribed to older people.

In silico design of novel proton-pump inhibitors with reduced adverse effects.

The development of new proton-pump inhibitors (PPIs) with less adverse effects by lowering the pKa values of nitrogen atoms in pyrimidine rings has been previously suggested by our group. In this work, we proposed that new PPIs should have the following features: (1) number of ring II = number of ring I + 1; (2) preferably five, six, or seven-membered heteroatomic ring for stability; and (3) 1 < pKa1 < 4. Six molecular scaffolds based on the aforementioned criteria were constructed, and R groups were extracted from compounds in extensive data sources. A virtual molecule dataset was established, and the pKa values of specific atoms on the molecules in the dataset were calculated to select the molecules with required pKa values. Drug-likeness screening was further conducted to obtain the candidates that significantly reduced the adverse effects of long-term PPI use. This study provided insights and tools for designing targeted molecules in silico that are suitable for practical applications.

Transoral incisional fundoplication for reflux after peroral endoscopic myotomy: a crucial addition to our arsenal.

Introduction Increased esophageal acid exposure is seen in a large percentage of patients with achalasia who undergo peroral endoscopic myotomy (POEM). Endoscopic transoral fundoplication (TIF) is a novel endoscopic technique for the management of patients with chronic gastroesophageal reflux (GERD). We present the first case series evaluating the role of TIF post-POEM. Methods Consecutive patients 18 years or older from our academic institution who underwent a POEM procedure and subsequently underwent TIF for symptomatic reflux or regurgitation between December 2014 and June 2017 were included. The primary outcome was discontinuation of proton-pump inhibitor (PPI) use and healing of esophagitis (when initially present) on post-procedure esophagogastroduodenoscopy (EGD). Technical success was defined as successful completion of the endoscopic fundoplication. Adverse events (AEs) were recorded for all patients. Results Five patients were included (60 % male, average age 55 ± 14 years). Technical success was achieved in 100 % of patients. Discontinuation of PPI use was achieved in 5/5 patients (100 %). Three patients had esophagitis pre-procedure and all were noted to have resolution of inflammation on post-procedure EGD. No adverse events were noted. Mean follow-up time was 27 months (range 5 – 34 months). Conclusion TIF post-POEM appears feasible, safe, and efficacious in improving symptoms and esophagitis, decreasing long-term risks of acid exposure, and decreasing risks of long-term PPI use in patients post-POEM in this small cohort of patients. Larger studies are needed to confirm these initial findings.

Functional hypoparathyroidism secondary to magnesium deficiency in long-term users of proton pump inhibitor

Gastroesophageal reflux disease (GERD) is a gastrointestinal motility disorder that results from the reflux of stomach contents into the esophagus resulting in symptoms or complications. GERD is now widely prevalent around the world, with clear evidence of increasing prevalence in many developing countries. Treatment for most people with GERD includes lifestyle changes and medication. Proton pump inhibitors (PPIs) are a mainstay therapy for all gastric acid-related diseases. Long-term use of PPIs is associated with hypomagnesaemia, hypokalemia, hypocalcaemia, osteoporosis and bone fractures, chronic renal disease, acute renal disease, and other. Clinical concerns arise from a small but growing number of case reports presenting PPI-induced hypomagnesaemia. In 2011 the U.S. Food and Drug Administration is informing the public that prescription PPI may cause low serum magnesium levels if taken for prolonged periods of time.&#x0D; In this article, we present the case of a 56-year-old patient with muscle cramps, violation of cardiac rhythm, lethargy and other caused by hypomagnesaemia, hypocalcaemia and hypokalemia with a low parathyroid hormone level while using a PPI. After magnesium repletion abnormalities resolved. A causal relation with PPI use was supported by the recurrence of hypomagnesaemia after re-challenge.

Treatment of patients with erosive esophagitis. A modern view on the problem

Gastroesophageal reflux disease is one of the most common diseases of the gastroenterological profile. There are several forms of illness, including non-erosive forms, erosive esophagitis, Barrett esophagus. The article provides an overview of the drugs used to treat the erosive form of GERD and long-term supportive therapy from the perspective of evidence-based medicine. The main objectives of the treatment of erosive esophagitis are to heal esophagus mucosa lesions, achieve long-term remissions, and normalize the patients’ life quality. The proton pump inhibitors (PPIs) have steadily become the mainstay in treatment of erosive esophagitis. These drugs are used at all stages of treatment, both for the relief of symptoms and healing of oesophagus mucosa lesions, and as the long-term supportive therapy. Due to the need for long-term use of IPI, their safety are open to question. The recent publications reported an increased risk of chronic kidney disease, myocardial infarction, pneumonia, calcium, magnesium, iron, vitamin B12 deficiency. At the same time, the analysis of studies underlying the risks of long-term PPI use detected some significant disadvantages that reduce their evidence-based value. This paper provides data on the most frequently discussed risks and critical assessment of them.

Proton pump inhibitors not associated with hypomagnesemia, regardless of dose or concomitant diuretic use.

Proton pump inhibitors (PPIs) are among the most commonly prescribed medications worldwide, with dramatic efficacy for upper gastrointestinal acid-related disorders. In recent years, however, the safety of long-term PPI use has been questioned. One issue based on scant and conflicting literature is the possibility of PPI-related hypomagnesemia. Our purpose was to assess for any clinically significant alteration in serum magnesium levels in large groups of patients taking different PPIs in varying doses, with or without diuretics. This was a retrospective review of patient records at time of hospitalization, from February 2012 to December 2014. Two thousand four hundred patients were randomly selected from a pool of 12058 magnesium levels performed at or within 24h of hospital admission. Patients were categorized in six groups based on outpatient PPI and/or diuretic use. The main outcome studied was hypomagnesemia, defined as serum magnesium level<1.6mg/dL. Mean magnesium levels were normal in PPI users (1.84±0.29mg/dL [normal 1.6 to 2.5mg/dL]) and PPI nonusers (1.85±0.30mg/dL), P=0.40, and there was no statistical difference in the prevalence of hypomagnesemia (14.7% vs 15.1%, P=0.77). In separate groups, there were also no significant differences in serum magnesium levels between those taking PPIs of varying doses, with or without concomitant diuretics, and those not taking PPIs or diuretics. Regardless of PPI dosage or concomitant diuretics prescribed, magnesium levels were unaffected. Routine screening of serum magnesium in PPI patients appears unnecessary.

Advantages and Disadvantages of Long-term Proton Pump Inhibitor Use.

Proton pump inhibitors (PPIs) potently inhibit gastric acid secretion and are widely used for treatment of acid-related diseases including gastroesophageal reflux disease and secondary prevention of aspirin/NSAID-induced ulcers. Although clinically important adverse effects of PPIs can occur, just as with other drugs, those are not frequently observed during or after administration. Thus, PPIs are regarded as relatively safe and considered to be clinically beneficial. Recently, PPIs have become frequently administered to patients with functional gastrointestinal diseases or primary prevention of drug-related gastroduodenal damage, even though their beneficial effects for those conditions have not been fully confirmed. PPIs tend to be given for conditions in which the necessity of the drug has not been clarified, thus otherwise rare adverse effects are presented as clinically relevant. Although several PPI-related adverse effects have been reported, their clinical relevance is not yet clear, since the evidence reported in those studies is not at a high enough level, as the majority are based on retrospective observational studies and the reported hazard ratios are low. It is important to administer PPIs only for patients who will gain a substantial clinical benefit and to continue to investigate their adverse effects with high quality prospective studies.

Long-term proton pump inhibitor therapy leads to small bowel bacterial overgrowth as determined by breath hydrogen and methane excretion

Objectives: Prolonged suppression of gastric acid secretion by proton pump inhibitors (PPIs) may alter the bacterial microbiota of the upper gastrointestinal tract and lead to small bowel bacterial overgrowth (SBBO). Published reports have shown conflicting results on the association between PPI therapy and risk of SBBO development. We evaluated whether long-term PPI treatment is associated with presence of SBBO as determined by breath hydrogen (H2) and methane (CH4) excretion. We also assessed the differences in H2/CH4 excretion patterns in patients taking PPI compared with those not taking the medication and searched for the potential predictors of a positive breath test result. Material and methods: This was a prospective cohort study that included 67 PPI-treated patients (PPIT) and 62 not-receiving PPI (C, comparison). PPIT and C underwent a glucose H2/CH4 breath test (HMBT) to determine the presence of SBBO. Results: The prevalence of SBBO was significantly higher in PPIT compared to C (44.8% versus 21%, p = 0.005, OR = 3.06, 95% CI 1.40–6.66) as determined by H2 and CH4 excretion. We found that PPIT had all H2 test parameters (baseline H2 levels, maximum peak of H2 as well as mean H2 through the whole test) significantly higher than C. Even those PPIT who did not meet the criteria of breath test positivity had statistically higher breath H2 levels compared to C. Although we did not observe significant differences in CH4 excretion between groups, 19.4% of PPIT and 12.9% of C would have had a false-negative HMBT results had CH4 not been taken into account. Conclusions: Long-term PPI use was found to be significantly associated with SBBO development as determined by breath H2 and CH4 excretion. CH4 determination reduces the number of falsely negative test results.

Proton pump inhibitor use and risk of hip fractures among community-dwelling persons with Alzheimer's disease-a nested case-control study.

Hip fractures are a major health concern among older persons with Alzheimer's disease, who usually use many concomitant drugs for several diseases. Evidence of the association between proton pump inhibitor use and risk of hip fracture is contradictory. To investigate whether the long-term use of proton pump inhibitor is associated with risk of hip fractures among community-dwelling persons with Alzheimer's disease. In this nested case-control study, the nationwide MEDALZ data were utilised. Community-dwelling persons with Alzheimer's disease who encountered incident hip fracture (N=4818; mean age 84.1) were included as cases. Four controls were matched for each case at the date of hip fracture (N=19235; mean age 84.0). The association between hip fracture and duration of current PPI use (ongoing use during 0-30days before the index date), and cumulative duration of use during 10years before was investigated with conditional logistic regression. Long-term or cumulative proton pump inhibitor use was not associated with an increased risk of hip fracture. Current proton pump inhibitor use was associated with an increased risk of hip fracture (adjusted OR 1.12, 95% CI 1.03-1.22). The risk was increased in short-term current use (<1year) (adjusted OR 1.23, 95% CI 1.10-1.37). The increased risk of hip fracture was evident only in short-term proton pump inhibitor use, but no association was found for long-term or cumulative use. Thus, our findings do not support previous assumptions that long-term proton pump inhibitor use would be associated with an increased risk of hip fractures.

Fall-Risk-Increasing Drugs: A Systematic Review and Meta-analysis: III. Others

Background and objectiveThe use of psychotropic medication and cardiovascular medication has been associated with an increased risk of falling. However, other frequently prescribed medication classes are still under debate as potential risk factors for falls in the older population. The aim of this systematic review and meta-analysis is to evaluate the associations between fall risk and nonpsychotropic and noncardiovascular medications. Methods and designA systematic review and meta-analysis. A search was conducted in Medline, PsycINFO, and Embase. Key search concepts were “falls,” “aged,” “medication,” and “causality.” Studies were included that investigated nonpsychotropic and noncardiovascular medications as risk factors for falls in participants ≥60 years or participants with a mean age ≥70 years. A meta-analysis was performed using the generic inverse variance method, pooling unadjusted and adjusted odds ratio (OR) estimates separately. ResultsIn a qualitative synthesis, 281 studies were included. The results of meta-analysis using adjusted data were as follows (a pooled OR [95% confidence interval]): analgesics, 1.42 (0.91-2.23); nonsteroidal anti-inflammatory drugs (NSAIDs), 1.09 (0.96-1.23); opioids, 1.60 (1.35-1.91); anti-Parkinson drugs, 1.54 (0.99-2.39); antiepileptics, 1.55 (1.25-1.92); and polypharmacy, 1.75 (1.27-2.41). Most of the meta-analyses resulted in substantial heterogeneity that did not disappear after stratification for population and setting in most cases. In a descriptive synthesis, consistent associations with falls were observed for long-term proton pump inhibitor use and opioid initiation. Laxatives showed inconsistent associations with falls (7/20 studies showing a positive association). ConclusionOpioid and antiepileptic use and polypharmacy were significantly associated with increased risk of falling in the meta-analyses. Long-term use of proton pump inhibitors and opioid initiation might increase the fall risk. Future research is necessary because the causal role of some medication classes as fall-risk-increasing drugs remains unclear, and the existing literature contains significant limitations.

Maintenance proton pump inhibition therapy and risk of oesophageal cancer

BackgroundThe association of long-term use of proton pump inhibitors (PPIs) with oesophageal adenocarcinoma has been poorly defined. Our aim was to assess the risk of oesophageal cancer assessing confounding by indication. MethodsThis population-based cohort study included all 796,492 adults exposed to maintenance therapy with PPIs in Sweden in 2005–2012. Standardised incidence ratios (SIRs) and 95% confidence intervals (CIs) were calculated to assess the risk of oesophageal adenocarcinoma (and squamous cell carcinoma as a comparison) among long-term PPI users relative to the corresponding background population. The different indications for maintenance PPI therapy were analysed separately. ResultsAmong all individuals using maintenance PPI therapy, the overall SIR of oesophageal adenocarcinoma was 3.93 (95% CI 3.63–4.24). The SIRs of adenocarcinoma were increased also among individuals without gastro-oesophageal reflux disease who used PPIs for indications not associated with any increased risk of oesophageal adenocarcinoma. For example, the SIRs among participants using maintenance PPI therapy because of maintenance treatment with non-steroidal anti-inflammatory drugs and aspirin were 2.74 (95% CI 1.96–3.71) and 2.06 (95% CI 1.60–2.60), respectively. The SIRs of oesophageal squamous cell carcinoma were increased for most investigated indications, but to a lesser degree than for oesophageal adenocarcinoma. ConclusionIn conclusion, the long term use of PPIs is associated with increased risk of oesophageal adenocarcinoma in the absence of other risk factors. Long term use of PPIs should be addressed with caution.

A Concise Review on Extensive use of Proton Pump Inhibitors

Proton Pump inhibitors have been a landmark since their inception through their safe and efficacious use in inhibition of acid secretion. They superseded another class of drugs that serve the same purpose but with a different mode of action termed “H2 receptor antagonists”. PPI’s (Proton pump inhibitors) prescribing has been dramatically increased over the years owing to their role in treating acid related disorders like GERD (Gastro Esophageal Reflux Disease), Gastric and Duodenal Ulcers, NSAID (Non-Steroidal Anti Inflammatory Drugs) induced ulcers etc. They are available as over the counter medications in many countries. But, the long-term use of PPi’s (Proton pump inhibitors) have certain limitations that has been extensively studied. Deprescribing has been suggested to reduce polypharmacy where the PPi (Proton pump inhibitors) use may be inappropriate or without indication. The present article emphasizes the need for PPi ((Proton pump inhibitors) use with possible indications along with various de-prescribing methods along with possible safety and acceptable efficacy profile of PPi’s (Proton pump inhibitors) in long term use. Recent novel studies are being aimed at reducing nocturnal acid secretion4 that conventional PPi’s (Proton pump inhibitors) couldn’t address where Potassium Competitive acid blockers (PCAB) come into play.

The relationship between proton pump inhibitors and renal disease.

ABSTRACTProton pump inhibitors (PPIs) bind to enzyme H+/K+-ATPase and inhibit its activity in the stomach, thus decreasing the secretion of gastric acid. PPIs may trigger acute interstitial nephritis, a potentially severe adverse event commonly associated with acute kidney injury. Studies have found that prolonged use of PPIs may increase the risk of chronic kidney disease (CKD). The increase in prescription and inadequate use of this class of medication calls for studies on the effects of prolonged PPI therapy on renal function. Therefore, this review aimed to analyze recent studies on the matter and discuss the possible consequences of the long-term use of PPIs on renal function.

Long-Term Proton Pump Inhibitor Administration Caused Physiological and Microbiota Changes in Rats

Background: Proton pump inhibitors (PPIs) are used for the long-term treatment of gastroesophageal disorders and the non-prescription medicines for acid reflux. However, there is growing concerns about PPI misuse, overuse and abuse. This study aimed to develop an animal model to examine the effects of long-term use of PPI in vivo. Methods: Twenty-one Wistar rats were given omeprazole orally for 30 days. After euthanization, the serum and stool were collected to perform MS-based quantitative analysis of metabolites. We carried out 16S rRNA gene profiling of fecal microbiota, assessed the expression of bile acid metabolism regulators and examined the immunopathological characteristics of bile ducts. Findings: After long-term PPI exposure, the fecal microbial and metabolites profile was altered and showed similarity to those observed in high-fat diet studies. Surprisingly, morphological changes were observed in the bile duct, including ductal epithelial proliferation, micropapillary growth of biliary epithelium, focal bile duct stricture formation and bile duct obstruction. These are characteristics of precancerous lesions of bile duct. FXR and RXRα expressions were significantly reduced, which were similar to that observed in cholangiocarcinoma in TCGA and Oncomine databases. Interpretation: We established a novel animal model to examine the effects of long-term use of omeprazole. The gut microbes, metabolic change and biliary epithelial hyperplasia are consequences of long-term PPI exposure. And the results showed the environment in vivo tends to a high-fat diet. Funding Statement: This work was financially supported in part by a grant from Taipei Medical University, Taiwan (TMU105-AE1-B41), a grant from Ministry of Science and Technology, Taiwan (MOST106-2320-B-038-005) and the “TMU Research Center of Cancer Translational Medicine” from The Featured Areas Research Center Program within the framework of the Higher Education Sprout Project by the Ministry of Education (MOE) in Taiwan. Declaration of Interests: The authors declare that they have no competing interests. Ethics Approval Statement: All animals were maintained and handled in an accredited facility in accordance with IACUC (Institutional Animal Care and Use Committee) guidelines and institutional ethics review board approval.

Emerging hazard effects of proton pump inhibitor on the risk of colorectal cancer in low-risk populations: A Korean nationwide prospective cohort study.

PurposeDespite plausible mechanisms, the clinical significance of long-term proton pump inhibitor (PPI) use to colorectal cancer (CRC) remains unknown. The purpose of this study was to investigate the association between PPI use and CRC development.MethodsWe conducted a population-based prospective cohort study using the Korean nationwide claims database merged with national health examination data. The study cohort included a total of 451,284 participants who were tracked to identify cases of CRC since 2007. We assessed and standardized PPI use before the index date using the Defined Daily Dose system. We calculated the hazard ratios and their 95% confidence intervals to assess the association between PPI use and CRC occurrence using Cox proportional hazard regression models with adjustment for potential confounders. We performed subgroup analyses of the effect of PPI exposure on CRC development stratified by the CRC risk.ResultsThere were 5,304 cases of CRC during the study period of 2,908,152 person-years. PPI use was not associated with CRC risk overall. The incidence of CRC was higher among individuals who were elderly, male, more obese, and drank alcohol more frequently and among those who had more comorbidities. Further subgroup analyses revealed that the hazard effect of PPI use increased linearly in a dose-dependent manner with the number of CRC risk factors for which the risk level was considered low.ConclusionWithin the low-risk population, PPI use was associated with an increased risk of CRC, although the association did not weigh the effects of conventional risk factors.

Proton Pump Inhibitors and Dementia: Deciphering the Data.

Proton pump inhibitors (PPIs) are effective and suppressing acid, and therefore have efficacy against gastric acid-related disorders. The long-term safety of PPIs is less clear and there have been a number of studies raising concerns regarding risk of pneumonia, fracture, Clostridium difficile, chronic renal failure, and dementia. This latter concern is addressed by a study in this issue of AJG using health care registry data and found there was no association between PPI use and Alzheimer's dementia. Furthermore, there was no increased risk of dementia with long-term use of PPIs or higher doses of PPIs. Discrepancies between studies probably relate to multiple testing and residual confounding and currently there is insufficient evidence to suggest that the association between PPIs and dementia is causal.

What is the long term acid inhibitor treatment in gastroesophageal reflux disease? What are the potential problems related to long term acid inhibitor treatment in gastroesophageal reflux disease? How should these cases be followed?

The meta-analyses of observational studies (OBS) showed the risk of any fracture and hip fracture slightly increased with proton pump inhibitor (PPI) treatment depending on the dose and regardless of time. This was not observed with histamine-2 receptor antagonists (H2RA). The risk of bacterial overgrowth and spontaneous bacterial peritonitis were increased with PPI therapy, but not with H2RA. In meta-analyses of OBS, a slight increase was observed in the risk of community-acquired pneumonia (CAP) in the early stages (<1 month) of PPI use and particularly at high doses. In a five-year LOTUS study, no difference was found in vitamin B12, folic acid, vitamin D, and calcium values in terms of the initial and end of follow-up levels. No increase in the risk of premalignant gastric lesions was observed in the meta-analysis of RCTs in which PPI treatment (≥6 months) was given to Helicobacter pylori negative patients. The risk of hypomagnesemia with PPI use was increased in patients having GFR<60, using diuretics, and over 65 years of age. Quasi-experimental studies showed a reduced zinc absorption with PPI use. In the meta-analysis of OBS, long-term (>1 year) PPI use increased the risk of fundic polyps, but no risk was found in shorter use. The meta-analyses of RCTS showed no difference between PPI and surgery or placebo arms and between the arms of H2RA and placebo in terms of all side effects. No difference was found between the PPI and H2RA arms both in all and serious adverse effects.

Proton Pump Inhibitor Use and Dementia Risk: Prospective Population-Based Study.

To determine whether higher cumulative proton pump inhibitor (PPI) exposure is associated with greater dementia risk. Prospective population-based cohort study. Kaiser Permanente Washington, an integrated healthcare delivery system in Seattle, Washington. Individuals aged 65 and older without dementia at study entry (N = 3,484). Participants were screened for dementia every 2 years, and those who screened positive underwent extensive evaluation. Dementia outcomes were determined using standard diagnostic criteria. Time-varying PPI exposure was determined from computerized pharmacy data and consisted of total standardized daily doses (TSDDs) dispensed to an individual in the prior 10 years. We also assessed duration of use. Multivariable Cox regression was used to estimate the association between PPI exposure and time to dementia or Alzheimer's disease (AD). Over a mean follow-up of 7.5 years, 827 participants (23.7%) developed dementia (670 with possible or probable AD). PPI exposure was not associated with risk of dementia (P = .66) or AD (P = .77). For dementia, the risk for specific levels of cumulative exposure compared to no use was: 365 TSDDs (HR 0.87, 95% CI 0.65-1.18), 1,095 TSDDs (HR 0.99, CI 0.75-1.30) and 1,825 TSDDs (HR 1.13, CI 0.82-1.56). These TSDD levels represent approximately 1, 3 and 5 years of daily use respectively. Duration of PPI use was not associated with dementia outcomes either. Proton pump inhibitor use was not associated with dementia risk, even for people with high cumulative exposure. Although there are other safety concerns with long-term PPI use, results from our study do not support that these medications should be avoided out of concern about dementia risk.

Proton Pump Inhibitor Usage and the Risk of Mortality in Hemodialysis Patients

IntroductionLong-term inappropriate proton pump inhibitors use (PPIs) is a matter of concern because of the risks associated with their long-term use in older patients with chronic conditions. The risk of PPI treatment in hemodialysis patients remains unexplored.MethodsWe assessed the relationship between the use of PPIs and the risk of death in hemodialysis patients throughout a retrospective multicenter propensity score–matched study. Information about demographic, hemodialysis treatment, laboratory data, and concomitant medication was obtained from the EuCliD database (Fresenius Medical Care). We studied 1776 hemodialysis patients on PPI therapy compared to 466 patients not receiving PPIs. The resulting population comprising 2 groups of 410 matched patients was studied.ResultsPPI use was associated with hypomagnesemia (Mg <1.8 mg/dl (0.75 mmol/l); odds ratio [OR] = 2.70, 95% confidence interval [CI] = 1.38−5.27, P < 0.01). The exposure to PPIs in the full patient cohort was identified as an independent predictor for all-cause mortality in both univariate (HR = 3.16, 95% CI = 1.69–5.90, P < 0.01) and multivariate (HR = 2.70, 95% CI = 1.38–5.27, P < 0.01) Cox regression models. Moreover PPI use was identified as a predictor of CV mortality (HR = 1.51, 95% CI = 1.05−2.20, P = 0.03) Of the 820 patients matched throughout the propensity score analysis, the hazard ratios for all-cause mortality (HR = 1.412, 95% CI = 1.04–1.93, P = 0.03) and CV mortality (HR = 1.67, 95% CI = 1.03−2.71, P = 0.04) were higher among patients on PPIs versus those not on PPIs.ConclusionThe study data suggest that the PPI treatment should be regularly monitored and prescribed only when indicated.