Association of proton pump inhibitor use with renal outcomes in patients with coronary artery disease.
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ABSTRACT:
SUBMITTER: Cho NJ
PROVIDER: S-EPMC5875577 | biostudies-literature | 2018 Mar
REPOSITORIES: biostudies-literature
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Association of proton pump inhibitor use with renal outcomes in patients with coronary artery disease.
Cho Nam-Jun NJ Choi Chi-Young CY Park Samel S Park Sang-Ho SH Lee Eun Young EY Gil Hyo-Wook HW
Kidney research and clinical practice 20180331 1
<h4>Background</h4>Several studies have suggested that proton pump inhibitor (PPI) use is associated with adverse renal outcomes, but obvious evidence for this association is lacking. We investigated the association between PPI use and adverse renal outcomes in patients who had undergone percutaneous coronary intervention.<h4>Methods</h4>Of the 1,284 patients hospitalized for percutaneous coronary intervention between January 2007 and May 2012, 934 patients with baseline estimated glomerular fil ...[more]
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Project description:ObjectivesProton-pump inhibitors (PPIs) seem to increase the incidence of cardiovascular events in patients with coronary artery disease (CAD), mainly in those using clopidogrel. We analysed the impact of PPIs on the prognosis of patients with stable CAD.MethodsWe followed 706 patients with CAD. Primary outcome was the combination of secondary outcomes. Secondary outcomes were 1) acute ischaemic events (any acute coronary syndrome, stroke, or transient ischaemic attack) and 2) heart failure (HF) or death.ResultsPatients on PPIs were older [62.0 (53.0-73.0) vs. 58.0 (50.0-70.0) years; p = 0.003] and had a more frequent history of stroke (4.9% vs. 1.1%; p = 0.004) than those from the non-PPI group, and presented no differences in any other clinical variable, including cardiovascular risk factors, ejection fraction, and therapy with aspirin and clopidogrel. Follow-up was 2.2±0.99 years. Seventy-eight patients met the primary outcome, 53 developed acute ischaemic events, and 33 HF or death. PPI use was an independent predictor of the primary outcome [hazard ratio (HR) = 2.281 (1.244-4.183); p = 0.008], along with hypertension, body-mass index, glomerular filtration rate, atrial fibrillation, and nitrate use. PPI use was also an independent predictor of HF/death [HR = 5.713 (1.628-20.043); p = 0.007], but not of acute ischaemic events. A propensity score showed similar results.ConclusionsIn patients with CAD, PPI use is independently associated with an increased incidence of HF and death but not with a high rate of acute ischaemic events. Further studies are needed to confirm these findings.
| S-EPMC5245803 | biostudies-literature
Project description:ObjectiveProton pump inhibitor (PPI) use has been associated with reduced diversity of the gut microbiome and may lead to worse clinical outcomes in inflammatory bowel disease (IBD). We aimed to evaluate whether PPI use affects clinical outcomes in a real-world setting.DesignHealthcare claims data of adult IBD patients were obtained from the IBM MarketScan Database. Multivariable analysis and propensity score-matched analysis were performed to assess associations between PPI use and new biologic start, and IBD-related hospitalizations and surgeries.ResultsA total of 46,234 IBD patients were identified (6,488 (14%) and 39,746 (86%) patients with and without PPI, respectively). Patients on PPI were more likely to be older, female, and smokers and less likely to be on immunomodulators. Multivariable analyses demonstrated that PPI use was associated with new biologic start (odds ratio (OR) 1.11, 95% confidence interval (CI) 1.04-1.18), and IBD-related admissions (OR 1.95, 95% CI 1.74-2.19) and surgeries (OR 1.46, 95% CI 1.26-1.71). Following propensity score matching, patients on PPI remained more likely to start a new biologic (23% vs 21%, p = 0.011), and have IBD-related admissions (8% vs 4%, p < 0.001) and surgeries (4% vs 2%, p < 0.001). Subgroup analyses stratified by age, smoking, and glucocorticoid use showed similar results. There was a dose-response relationship between the number of PPI prescriptions and the risk of new biologic use (p < 0.001) and IBD-related admissions (p < 0.001).ConclusionPPI use was associated with worse clinical outcomes in patients with IBD in the real-world setting. Further studies are warranted to validate these findings, but caution may be needed when prescribing a PPI to IBD patients.Study highlights WHAT IS KNOWNProton pump inhibitors (PPIs) are one of the most prescribed therapies in the United States (US).Reduction of gastric acid secretion by PPI use increases the risk of imbalance in gut microbiota composition and may increase the risk of enteric infections.Recent studies have reported that the use of PPI was associated with development of inflammatory bowel disease (IBD) and reduced rates of remission in patients on infliximab therapy, which may be due to alterations of intestinal microbiota.WHAT IS NEW HEREIn a large real-world US healthcare database study, IBD patients with PPI use were more likely to have a new biologic medication started, have an IBD-related surgery, and have an IBD-related hospitalization, which remained significant after adjusting for confounders by multivariable analysis, propensity-score matched analysis, and subgroup analysis.Appropriate clinical review of PPI necessity may need to be performed in patients with IBD when considering prescribing a PPI or who are already on PPI therapy.
| S-EPMC10124315 | biostudies-literature
Project description:Background & aimsStudies have reported associations between proton pump inhibitor (PPI) use and dementia. However, data are lacking on long-term PPI use and cognitive function. We therefore examined associations between PPI use and performance in tests of cognitive function. Because of shared clinical indications, we examined associations for H2 receptor antagonists (H2RAs) as a secondary aim.MethodsWe used prospectively collected data on medication use and other potential risk factors from 13,864 participants in the Nurses' Health Study II who had completed a self-administered computerized neuropsychological test battery. Multivariable linear regression models were used to examine associations between medication use and composite scores of psychomotor speed and attention, learning and working memory, and overall cognition.ResultsWe observed a modest association between duration of PPI use and scores for psychomotor speed and attention (mean score difference for PPI use of 9-14 years vs never users, -0.06; 95% confidence interval, -0.11 to 0.00; Ptrend = .03). After controlling for H2RA use, the magnitude of this score difference was attenuated. Among individuals who did not use PPIs regularly, duration of H2RA use was associated with poorer cognitive scores, with the strongest association apparent for learning and working memory (mean score difference for H2RA users of 9-14 years vs never users, -0.20; 95% confidence interval, -0.32 to -0.08; Ptrend < .001).ConclusionsIn an analysis of data from the Nurses' Health Study II, we did not observe a convincing association between PPI use and cognitive function. Our data do not support the suggestion that PPI use increases dementia risk. Because our primary hypothesis related to PPI use, our findings for H2RAs should be interpreted with caution.
| S-EPMC5623145 | biostudies-literature
Project description:BackgroundProton pump inhibitors (PPIs) are frequently prescribed to patients with coronary heart disease (CHD) under antiplatelet therapy to prevent gastrointestinal (GI) bleeding. However, its clinical impact is still under debate, especially in Asian population. This study was undertaken to explore the effects of concurrent use of clopidogrel and PPIs on the clinical outcomes in Chinese patients with CHD in secondary prevention.MethodsA single-center retrospective study was conducted in 638 patients with CHD on consecutive clopidogrel therapy for at least 1 year. After 18-month follow-up, adverse clinical events were collected. Cox regression was used to calculate hazard ratios (HR) and 95% confidence interval (CI) for the effect of PPI use on the outcomes. A total of 638 patients were recruited from 2014 to 2015 in this study, among whom 201 were sustained PPI users, 188 were intermittent PPI users and the remaining 249 were non-PPI users.ResultsCompared with sustained PPI users, intermittent use of PPIs was associated with a lower risk of stroke, major adverse cardiac events (MACE) and net adverse clinical event (NACE) (stroke: adjusted HR: 0.109, 95% CI 0.014-0.878, p = 0.037; MACE: adjusted HR: 0.293, 95% CI 0.119-0.722; p = 0.008; NACE: adjusted HR: 0.357, 95% CI 0.162-0.786, p = 0.011). Subgroup analysis further revealed the benefit of intermittent PPI use was significant in male CHD patients over 60 years old, with hypertension or chronic kidney disease, and undergoing percutaneous coronary intervention during hospitalization.ConclusionThe current findings suggest that the intermittent concurrent use of PPIs and clopidogrel is not associated with an increased risk of 18-month adverse clinical outcomes, and intermittent use of PPIs is associated with a lower rate of MACE and NACE.
| S-EPMC7863361 | biostudies-literature
Project description:ImportanceProton pump inhibitor (PPI) use has been linked to increased risk of fracture in adults. Despite a trend in prescription of PPIs in children, there is scarce evidence regarding this safety concern in pediatric patients.ObjectiveTo evaluate the association between PPI use and risk of fracture in children.DesignThis nationwide register-based cohort study included data from Sweden from July 2006 to December 2016. Children younger than 18 years who initiated PPI use were matched on propensity score and age with those who did not initiate PPI use.ExposureInitiation of PPI use.Main outcomes and measuresCox regression was adopted to estimate hazard ratios (HRs) for a first fracture of any type and 5 subtypes of fracture, with follow-up for up to 5 years. To address potential residual confounding, high-dimensional propensity score matching and a direct comparison with histamine-2 receptor antagonists were performed.ResultsThere were a total of 115?933 pairs of children included. During a mean (SD) of 2.2 (1.6) years of follow-up, 5354 and 4568 cases of any fracture occurred among those who initiated PPIs vs those who did not, respectively (20.2 vs 18.3 events per 1000 person-years; hazard ratio [HR], 1.11 [95% CI, 1.06-1.15]). Use of PPIs was associated with increased risk of upper-limb fracture (HR, 1.08 [95% CI, 1.03-1.13]), lower-limb fracture (HR, 1.19 [95% CI, 1.10-1.29]), and other fractures (HR, 1.51 [95% CI, 1.16-1.97]) but not head fracture (HR, 0.93 [95% CI, 0.76-1.13]) or spine fracture (HR, 1.31 [95% CI, 0.95-1.81]). The HRs for fracture according to cumulative duration of PPI use were 1.08 (95% CI, 1.03-1.13) for 30 days or less, 1.14 (95% CI, 1.09-1.20) for 31 to 364 days, and 1.34 (95% CI, 1.13-1.58) for 365 days or more. The association was consistent in most sensitivity analyses, including high-dimensional propensity score matching (HR, 1.10 [95% CI, 1.06-1.15]), although the analysis of PPI vs histamine-2 receptor antagonist did not reach statistical significance (HR, 1.06 [95% CI, 0.97-1.15]).Conclusions and relevanceIn this large pediatric cohort, PPI use was associated with a small but significant increased risk of any fracture. Risk of fracture should be taken into account when weighing the benefits and risks of PPI treatment in children.
| S-EPMC7076540 | biostudies-literature
Project description:Proton pump inhibitors (PPIs) are commonly used as a supplement to cancer therapy. Yet, their effect on cancer mortality is largely unknown. Using data from Danish nationwide registries and Cox models regressing of both propensity scores and drug use, we estimated hazard ratios (HRs) with 95% confidence intervals (CIs) for cancer-specific and noncancer death among PPI users (≥2 prescriptions within six months after diagnosis; n = 36,066) compared with nonusers (<2 prescriptions, n = 311,853) or users of histamine H2 -receptor antagonists (H2 RA; n = 5,152). Adjusted HRs for cancer-specific mortality among postdiagnostic PPI users as compared with nonusers or H2 RA users were 1.29 (95% CI, 1.27-1.32) and 1.15 (95% CI, 1.10-1.20), respectively. HRs for cancer mortality associated with PPI use were highest for ovarian (1.35; 95% CI, 1.20-1.52) and lowest for esophageal cancer (0.91; 95% CI, 0.81-1.04). The associations were stronger among new PPI users after cancer diagnosis, indicating potential confounding. To test the effect of PPIs on tumor growth in a model system free for confounding factors, we investigated the effect of pantoprazole on tumor growth in mice. Pantoprazole (5 mg/kg/day) enhanced tumor growth (p = 0.033) and reduced the antitumor activity of gemcitabine (p = 0.008) in fibrosarcoma-bearing Balb/c mice, but not in immunodeficient Balb/c nude mice. In breast carcinoma-bearing FVB/N mice, pantoprazole had no effect on tumor growth alone but it reduced the life-prolonging effect of doxorubicin significantly (p = 0.007). Taken together, these data raise concerns about the increasing use of PPIs and calls for further studies addressing their safety among cancer patients.
| S-EPMC7611279 | biostudies-literature
Project description:Observational studies evaluating the possible interaction between proton pump inhibitors (PPIs) and clopidogrel have shown mixed results. We conducted a systematic review comparing the safety of individual PPIs in patients with coronary artery disease taking clopidogrel.Studies performed from January 1995 to December 2013 were screened for inclusion. Data were extracted, and study quality was graded for 34 potential studies. For those studies in which follow-up period, outcomes, and multivariable adjustment were comparable, meta-analysis was performed.The adjusted odds or hazard ratios for the composite of cardiovascular or all-cause death, myocardial infarction, and stroke at 1 year were reported in 6 observational studies with data on individual PPIs. Random-effects meta-analyses of the 6 studies revealed an increased risk for adverse cardiovascular events for those taking pantoprazole (hazard ratio 1.38; 95% CI 1.12-1.70), lansoprazole (hazard ratio 1.29; 95% CI 1.09-1.52), or esomeprazole (hazard ratio 1.27; 95% CI 1.02-1.58) compared with patients on no PPI. This association was not significant for omeprazole (hazard ratio 1.16; 95% CI 0.93-1.44). Sensitivity analyses for the coronary artery disease population (acute coronary syndrome versus mixed) and exclusion of a single study due to heterogeneity of reported results did not have significant influence on the effect estimates for any PPIs.Several frequently used PPIs previously thought to be safe for concomitant use with clopidogrel were associated with greater risk of adverse cardiovascular events. Although the data are observational, they highlight the need for randomized controlled trials to evaluate the safety of concomitant PPI and clopidogrel use in patients with coronary artery disease.
| S-EPMC4845227 | biostudies-other
Project description:Recently, proton pump inhibitor (PPI) intake has been linked to acute kidney injury and chronic kidney disease. The objective of this study was to assess the effect of PPIs on renal function and rejection rate in kidney transplant patients. We performed a single center, retrospective analysis of 455 patients who received a kidney transplant between May 2010 and July 2015. Median follow-up time was 3.3 years. PPI prescription was assessed in half-year intervals. Primary outcome parameters were the estimated glomerular filtration rate (eGFR), change in the eGFR, and >30% and >50% eGFR decline for different time periods (up to four years post-transplantation). Our secondary outcome parameter was occurrence of biopsy proven acute rejection (BPAR) in the first two years after transplantation. Except for >30% eGFR decline from half a year to two years post-transplantation (p = 0.044) and change in the eGFR, >30% and >50% eGFR decline showed no association with PPI intake in our patient cohort (p > 0.05). Similarly, by analyzing 158 rejection episodes, BPAR showed no correspondence with mean daily PPI intake. We conclude that prolonged PPI intake has no relevant adverse effect on kidney transplant function or rejection rates. Polypharmacy, however, remains a problem in renal transplant recipients and it is thus advisable to question the necessity of PPI prescriptions when clear indications are missing.
| S-EPMC7019820 | biostudies-literature
Project description:HypothesisScreening for esophageal adenocarcinoma has focused on identifying Barrett esophagus (BE) in patients with severe, long-standing symptoms of gastroesophageal reflux disease (GERD). Unfortunately, 95% of patients who develop esophageal adenocarcinoma are unaware of the presence of BE before their cancer diagnosis, which means they never had been selected for screening. One possible explanation is that no correlation exists between the severity of GERD symptoms and cancer risk. We hypothesize that severe GERD symptoms are not associated with an increase in the prevalence of BE, dysplasia, or cancer in patients undergoing primary endoscopic screening.DesignCross-sectional study.SettingUniversity hospital.PatientsA total of 769 patients with GERD.InterventionsPrimary screening endoscopy performed from November 1, 2004, through June 7, 2007.Main outcomes measuresSymptom severity, proton pump inhibitor therapy, and esophageal adenocarcinogenesis (ie, BE, dysplasia, or cancer).ResultsEndoscopy revealed adenocarcinogenesis in 122 patients. An increasing number of severe GERD symptoms correlated positively with endoscopic findings of esophagitis (odds ratio, 1.05; 95% confidence interval, 1.01-1.09). Conversely, an increasing number of severe GERD symptoms were associated with decreased odds of adenocarcinogenesis (odds ratio, 0.94; 95% confidence interval, 0.89-0.98). Patients taking proton pump inhibitors were 61.3% and 81.5% more likely to have adenocarcinogenesis if they reported no severe typical or atypical GERD symptoms, respectively, compared with patients taking proton pump inhibitors, who reported that all symptoms were severe.ConclusionsMedically treated patients with mild or absent GERD symptoms have significantly higher odds of adenocarcinogenesis compared with medically treated patients with severe GERD symptoms. This finding may explain the failure of the current screening paradigm in which the threshold for primary endoscopic examination is based on symptom severity.
| S-EPMC4086744 | biostudies-literature
Project description:ImportanceProton-pump inhibitors (PPIs) have been associated with the risk of colonization with drug-resistant bacteria; however, possible confounding by lifestyle-associated factors and disease severity casts doubt on this association, and whether the risk is dose dependent is not known.ObjectivesTo assess the association between PPI use and the risk of acquiring drug-resistant Enterobacterales and to examine interactions with possible microbiome-altering agents.Design, setting, and participantsThis nested case-control study involved 2239 hospitalized adult (aged ≥18 years) patients identified from the microbiology laboratory database of Amsterdam University Medical Centers between December 31, 2018, and January 6, 2021. Patients in the case group had newly detected extended-spectrum β-lactamase (ESBL)- or carbapenemase-producing Enterobacterales (identified by clinical specimens). Risk-set sampling was used to assign patients with negative results for ESBL- and carbapenemase-producing Enterobacterales to the control group, who were then matched on a 5:1 ratio with patients in the case group by age and culture date. A second validation case-control study included matched pairs (1:1 ratio; 94 in each group) of patients who were prospectively enrolled.ExposuresProton pump inhibitor use and clinical data at 30 days (primary exposure) and 90 days (secondary exposure) before the date of culture.Main outcomes and measuresAdjusted incidence rate ratios (aIRRs) of ESBL- or carbapenemase-producing Enterobacterales acquisition by PPI dose and time risk windows (30 days for the primary outcome and 90 days for the secondary outcome) were estimated using conditional logistic regression models.ResultsAmong 2239 hospitalized patients (51.1% male; mean [SD] age, 60.9 [16.7] years), 374 were in the case group (51.6% male; mean [SD] age, 61.1 [16.5] years) and 1865 were in the matched control group (51.0% male; mean [SD] age, 60.9 [16.7] years). The aIRR for PPI use overall was 1.48 (95% CI, 1.15-1.91) at 30 days. Sensitivity analyses and the analysis of the pair-matched study with prospectively enrolled patients (aIRR, 2.96, 95% CI, 1.14-7.74) yielded similar results; findings were consistent in subgroups and corroborated by a negative-control exposure analysis. No association with microbiome-disturbing agents was found; laxatives and antibiotics were independently associated with a more than 2-fold increase in the risk of acquisition (antibiotics: aIRR, 2.78 [95% CI, 2.14-3.59]; laxatives: aIRR, 2.26 [95% CI. 1.73-2.94]).Conclusions and relevanceIn this study, after careful control for confounding and sensitivity analyses, PPI use was associated with increases in the risk of acquiring ESBL- or carbapenemase-producing Enterobacterales among adult hospitalized patients. These findings emphasize the need for judicious use of PPIs.
| S-EPMC9951039 | biostudies-literature