Response to "Comment on 'Proton pump inhibitors and dementia: A nationwide population-based study'".
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SUBMITTER: Pourhadi N
PROVIDER: S-EPMC10984444 | biostudies-literature | 2024 Mar
REPOSITORIES: biostudies-literature
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Response to "Comment on 'Proton pump inhibitors and dementia: A nationwide population-based study'".
Pourhadi Nelsan N Janbek Janet J Jensen-Dahm Christina C Gasse Christiane C Laursen Thomas Munk TM Waldemar Gunhild G
Alzheimer's & dementia : the journal of the Alzheimer's Association 20240106 3
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Project description: Not available
| S-EPMC10984490 | biostudies-literature
Project description:ObjectivesTo determine whether higher cumulative proton pump inhibitor (PPI) exposure is associated with greater dementia risk.DesignProspective population-based cohort study.SettingKaiser Permanente Washington, an integrated healthcare delivery system in Seattle, Washington.ParticipantsIndividuals aged 65 and older without dementia at study entry (N = 3,484).MeasurementsParticipants 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).ResultsOver 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.ConclusionProton 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.
| S-EPMC5809315 | biostudies-literature
Project description:BackgroundTo examine the association between regular use of proton pump inhibitors and the risk of incident dementia, including dementia subtypes, and whether the association differs between APOE genotypes.MethodsBased on a prospective analysis of data from the UK Biobank, 501,002 individuals (female, 54.4%) aged between 40 and 70 years, who had no prevalent dementia at baseline, were enrolled between 2006 and 2010 and followed up to 2018. We compared all-cause dementia, Alzheimer's disease (AD), and vascular dementia (VaD) incidence rates between proton pump inhibitor users and non-users by the Cox proportional hazard model.ResultsDuring 4,438,839 person-years of follow-up (median length of follow-up, 9.0 years), there were 2505 incident cases of all-cause dementia, including 932 cases of AD and 524 cases of VaD. The incident rate of all-cause dementia among proton pump inhibitor users was 1.06 events per 1000 person-years, compared with 0.51 events per 1000 person-years among non-users. After adjustment for multiple confounders and indications, the hazard ratios (HRs) of the proton pump inhibitor users were 1.20 (95% CI, 1.07-1.35) for incident all-cause dementia, 1.23 (95% CI, 1.02-1.49) for incident AD, and 1.32 (95% CI, 1.05-1.67) for incident VaD. In addition, the association between proton pump inhibitor use and all-cause dementia differed by APOE genotype (P for interaction = 0.048). Among APOE ε4 heterozygotes, the fully adjusted HR of proton pump inhibitor use was 1.46 (95% CI, 1.22-1.75) and 1.68 (95% CI, 1.36-2.07), especially for individuals aged 65 years and older.ConclusionsThe finding of this large population-based cohort study indicates that the use of proton pump inhibitors is associated with an increased risk of incident dementia, particularly among APOE ε4 heterozygotes.
| S-EPMC9434890 | biostudies-literature
Project description:BackgroundThe use of proton-pump inhibitors (PPIs) has grown worldwide, and there are concerns about increased unsubstantiated long-term use. The aim of the study was to describe the real-world use of PPIs over the past decade in an entire national population.MethodsThis was a nationwide population-based drug-utilization study. Patterns of outpatient PPI use among adults in Iceland between 2003 and 2015 were investigated, including annual incidence and prevalence, duration of use, and dose of tablet used (lower versus higher), as well as the proportion of PPI use attributable to gastroprotection.ResultsWe observed 1,372,790 prescription fills over the entire study period, of which 95% were for higher-dose PPIs. Annual incidence remained stable across time (3.3-4.1 per 100 persons per year), while the annual prevalence increased from 8.5 per 100 persons to 15.5 per 100 persons. Prevalence increased with patient age and was higher among women than men. Duration of treatment increased with patients' age (36% of users over 80 years remained on treatment after 1 year compared with 13% of users aged 19-39 years), and was longer among those initiating on a higher dose compared with a lower dose. The proportion of PPI users concurrently using nonsteroidal anti-inflammatory drugs decreased over the study period, while the proportion concurrently using acetylsalicylic acid, oral anticoagulants, or platelet inhibitors increased.ConclusionsIn this nationwide study, a considerable increase in overall outpatient use of PPIs over a 13-year period was observed, particularly among older adults. Patients were increasingly treated for longer durations than recommended by clinical guidelines and mainly with higher doses.
| S-EPMC5977421 | biostudies-literature
Project description:OBJECTIVE:Proton pump inhibitors (PPIs) are among the most commonly prescribed drugs. Concerns have been raised about a potentially increased risk of gastric cancer following long-term use. Our aim is to assess the risk of gastric cancer associated with PPI use, taking into account underlying indications. DESIGN:This is a population-based cohort study. Standardised incidence ratios (SIRs) and 95% CIs were calculated to compare the risk of gastric cancer among long-term PPI users with the corresponding background population, while taking confounding by indication into account. SETTING:Population-based study in Sweden (2005-2012). PARTICIPANTS:This study included virtually all adults residing in Sweden exposed to maintenance therapy with PPIs. EXPOSURE/INTERVENTION:Maintenance use of PPIs, defined as at least 180 days during the study period. Maintenance use of histamine 2 receptor antagonist was evaluated for comparison reasons. OUTCOME MEASURES:Gastric cancer (cardia and non-cardia), and subgroup analysis for gastric adenocarcinoma, as defined by the Swedish Cancer Registry. RESULTS:Among 797 067 individuals on maintenance PPI therapy, the SIR of gastric cancer was over threefold increased (SIR=3.38, 95% CI 3.23 to 3.53). Increased SIRs were found in both sexes and all age groups, but were especially increased among PPI users younger than 40 years (SIR=22.76, 95% CI 15.94 to 31.52). Increased SIRs were found for each indication studied, including those without an association with gastric cancer, for example, gastro-oesophageal reflux (SIR=3.04, 95% CI 2.80 to 3.31), and those with a supposedly decreased risk, for example, aspirin users (SIR=1.93, 95% CI 1.70 to 2.18). The association was similar for cardia and non-cardia gastric cancer. Analyses restricted to adenocarcinoma showed similar results to those for all gastric cancers. Long-term users of histamine 2 receptor antagonists, which have the same indications as PPIs, were not at any increased risk. CONCLUSIONS:Long-term PPI use might be an independent risk factor for gastric cancer. This challenges broad maintenance PPI therapy, particularly if the indication is weak.
| S-EPMC5665226 | biostudies-literature
Project description:IntroductionConcerns have been raised regarding the potential association between proton pump inhibitor (PPI) use and dementia.ObjectiveThis study aimed to examine this association in an Asian population.MethodsPatients initiating PPI therapy between January 1, 2000 and December 31, 2003 without a prior history of dementia were identified from Taiwan's National Health Insurance Research Database. The outcome of interest was all-cause dementia. Cox regression models were applied to estimate the hazard ratio (HR) of dementia. The cumulative PPI dosage stratified by quartiles of defined daily doses and adjusted for baseline disease risk score served as the primary variables compared against no PPI use.ResultsWe analyzed the data of 15726 participants aged 40 years or older and free of dementia at baseline. PPI users (n = 7863; average follow-up 8.44 years) had a significantly increased risk of dementia over non-PPI users (n = 7863; average follow-up 9.55 years) (adjusted HR [aHR] 1.22; 95% confidence interval: 1.05-1.42). A significant association was observed between cumulative PPI use and risk of dementia (P for trend = .013). Subgroup analysis showed excess frequency of dementia in PPI users diagnosed with depression (aHR 2.73 [1.91-3.89]), hyperlipidemia (aHR 1.81 [1.38-2.38]), ischemic heart disease (aHR 1.55 [1.12-2.14]), and hypertension (aHR 1.54 [1.21-1.95]).ConclusionsAn increased risk for dementia was identified among the Asian PPI users. Cumulative PPI use was significantly associated with dementia. Further investigation into the possible biological mechanisms underlying the relationship between dementia and PPI use is warranted.
| S-EPMC5310771 | biostudies-literature
Project description:BackgroundKidney transplant recipients are commonly prescribed proton-pump inhibitors (PPIs), but due to concern for polypharmacy, chronic use should be limited.ObjectiveThe objective was to describe PPI use in kidney transplant recipients beyond their first year of transplant to better inform and support deprescribing initiatives.DesignWe conducted a retrospective, population-based cohort study using linked health care databases.SettingThis study was conducted in Alberta, Canada.PatientsWe included all prevalent adult, kidney-only transplant recipients between April 2008 and December 2017 who received their transplant between May 2002 and December 2017.MeasurementsThe primary outcome was ongoing or new PPI use and patterns of use, including frequency and duration of therapy, and assessment of indication for PPI use.MethodsWe ascertained baseline characteristics, covariate information, and outcome data from the Alberta Kidney Disease Network (AKDN). We compared recipients with evidence of a PPI prescription in the 3 months prior to study entry to those with a histamine-2-receptor antagonist (H2Ra) fill and those with neither.ResultsWe identified 1823 kidney transplant recipients, of whom 868 (48%) were on a PPI, 215 (12%) were on an H2Ra, and 740 (41%) were on neither at baseline. Over a median follow-up of 5.4 years (interquartile range [IQR] = 2.6-9.3), there were almost 45 000 unique PPI prescriptions dispensed, the majority (80%) of which were filled by initial PPI users. Recipients who were on a PPI at baseline would spend 91% (IQR = 70-98) of their graft survival time on a PPI in follow-up, and nephrologists were the main prescribers. We identified an indication for ongoing PPI use in 54% of recipients with the most common indication being concurrent antiplatelet use (26%).LimitationsOur kidney transplant recipients have access to universal health care coverage which may limit generalizability. We identified common gastrointestinal indications for PPI use but did not include rare conditions due to concerns about the validity of diagnostic codes. In addition, symptoms suggestive of reflux may not be well coded as the focus of follow-up visits is more likely to focus on kidney transplant.ConclusionsMany kidney transplant recipients are prescribed a PPI at, or beyond, the 1-year post-transplant date and are likely to stay on a PPI in follow-up. Almost half of the recipients in our study did not have an identifiable indication for ongoing PPI use. Nephrologists frequently prescribe PPIs to kidney transplant recipients and should be involved in deprescribing initiatives to reduce polypharmacy.
| S-EPMC10865938 | biostudies-literature
Project description:BackgroundAlthough Proton pump inhibitors (PPIs) were mostly prescribed for gastrointestinal (GI) disease widely, there were numerous studies about PPIs and adverse renal outcome. Most evidence was to evaluate the risk of PPIs in patients with normal renal function and in the absence of the moderate to advanced chronic kidney disease (CKD). This study focuses on the accelerated progression of renal function following proton pump inhibitors (PPIs) use, and the increased risks of acute kidney injury (AKI) among moderate to advanced CKD (pre-ESRD) patients.Patients and methodsA retrospective cohort study was conducted by including adult patients with chronic kidney disease (CKD) stages 3b to 5 who initiated PPI or H2 blocker (H2B) therapy between 2011 and 2018. The risk of renal events was assessed using the Cox proportional hazard model to estimate the adjusted hazard ratio (HR) and 95% confidence interval (CI). Sensitivity analyses were performed, including propensity score matching, as-treated analysis, and subgroup analysis.ResultsThe cohort comprised 83,432 pre-ESRD patients, with 5,138 treated with H2B and 1,051 with PPIs. The progression to ESRD was significantly more likely in patients using PPIs compared to those using H2B (adjusted HR, 1.495; 95% CI: 1.198-1.867). Specifically, omeprazole (adjusted HR, 1.784; 95% CI: 1.079-2.951) and esomeprazole (adjusted HR, 1.847; 95% CI: 1.332-2.561) were associated with a notably higher risk of ESRD and AKI.ConclusionsThe study highlights the significance of the accelerated renal risk, especially for moderate to advanced CKD patients, when prescribing PPIs and to implicate the clinicians prescribed PPIs and H2B in pre-ESRD patients.
| S-EPMC11667990 | biostudies-literature
Project description:BackgroundSome evidence suggests that proton pump inhibitors (PPIs) are an under-appreciated risk factor for hypomagnesemia. Whether hospitalization with hypomagnesemia is associated with use of PPIs is unknown.Methods and findingsWe conducted a population-based case-control study of multiple health care databases in Ontario, Canada, from April 2002 to March 2012. Patients who were enrolled as cases were Ontarians aged 66 years or older hospitalized with hypomagnesemia. For each individual enrolled as a case, we identified up to four individuals as controls matched on age, sex, kidney disease, and use of various diuretic classes. Exposure to PPIs was categorized according to the most proximate prescription prior to the index date as current (within 90 days), recent (within 91 to 180 days), or remote (within 181 to 365 days). We used conditional logistic regression to estimate the odds ratio for the association of outpatient PPI use and hospitalization with hypomagnesemia. To test the specificity of our findings we examined use of histamine H2 receptor antagonists, drugs with no causal link to hypomagnesemia. We studied 366 patients hospitalized with hypomagnesemia and 1,464 matched controls. Current PPI use was associated with a 43% increased risk of hypomagnesemia (adjusted odds ratio, 1.43; 95% CI 1.06-1.93). In a stratified analysis, the risk was particularly increased among patients receiving diuretics, (adjusted odds ratio, 1.73; 95% CI 1.11-2.70) and not significant among patients not receiving diuretics (adjusted odds ratio, 1.25; 95% CI 0.81-1.91). We estimate that one excess hospitalization with hypomagnesemia will occur among 76,591 outpatients treated with a PPI for 90 days. Hospitalization with hypomagnesemia was not associated with the use of histamine H2 receptor antagonists (adjusted odds ratio 1.06; 95% CI 0.54-2.06). Limitations of this study include a lack of access to serum magnesium levels, uncertainty regarding diagnostic coding of hypomagnesemia, and generalizability of our findings to younger patients.ConclusionsPPIs are associated with a small increased risk of hospitalization with hypomagnesemia among patients also receiving diuretics. Physicians should be aware of this association, particularly for patients with hypomagnesemia. Please see later in the article for the Editors' Summary.
| S-EPMC4181956 | biostudies-literature
Project description:Numerous observational studies suggest associations between proton pump inhibitors (PPIs) and dementia, but causal relationships remain uncertain. Using large-scale genome-wide association study (GWAS) data, we performed univariable Mendelian randomization (UVMR) analysis to assess the causality between five PPI types, and all-cause dementia and its five subtypes. Confounders were controlled through multivariable MR (MVMR) analysis to isolate PPIs' direct effects on dementia. Heterogeneity and pleiotropy assessments, and leave-one-out analysis, were conducted to validate the robustness of our results. Initial UVMR estimates suggested that lansoprazole (odds ratio [OR] 1.291; 95%confidence interval [CI] 1.001-1.665; p = 0.049) and pantoprazole (OR 1.118; 95% CI 1.014-1.233; p = 0.025) potentially increased VD risk, with their respective direct associations also discovered in MVMR. Additionally, FTD was found to reversely increase rabeprazole use (OR 1.086; 95% CI 1.011-1.167; p = 0.023). However, after adjustment for the false discovery rate (FDR), none of these associations remained statistically significant (pFDR> 0.05). The robustness of our results is supported by consistent estimates across complementary MR methods and the absence of pleiotropy. Our study indicates no robust causality between PPI use and increased dementia risk. Thus, it is inappropriate to restrict clinically justified PPI prescriptions merely due to potential cognitive risks.
| S-EPMC11576989 | biostudies-literature