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Proton Pump Inhibitors, Histamine-2 Receptor Antagonists, and Hip Fracture Risk among Patients on Hemodialysis.

ABSTRACT: BACKGROUND AND OBJECTIVES:An association between proton pump inhibitor (PPI) use and hip fracture risk has been described in the general population, where the primary causative hypothesis focuses on impaired gastrointestinal calcium absorption. The impact of acid suppressor use on hip fracture risk in a high-risk subset, patients with ESKD requiring hemodialysis, is unknown and could help further distinguish the reason for higher susceptibility among PPI users. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:Using the US Renal Data System, we identified all hip fracture events recorded between 2009 and 2014 among patients dependent on hemodialysis. Eligible cases were matched on index date with ten controls. We identified PPI and histamine-2 receptor antagonist use from Medicare Part D claims covering 3 years before the index date and stratified according to proportion of days covered by filled prescriptions. Using logistic regression with multiple imputation for missing data, we estimated unadjusted and multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs). RESULTS:We studied 4551 cases and 45,510 controls. Patients were older, more likely to be female and white, and had shorter dialysis vintage; fewer were obese. A larger proportion of patients had any prior PPI (70% versus 63%) or histamine-2 receptor antagonist (25% versus 23%) use. Use of PPI was associated with higher risk of hip fracture (adjusted OR, 1.19; 95% CI, 1.11 to 1.28). This association remained within subgroups of low, moderate, and high PPI use, yielding adjusted ORs of 1.16 (95% CI, 1.06 to 1.27), 1.21 (95% CI, 1.11 to 1.31), and 1.19 (95% CI, 1.08 to 1.31), respectively. CONCLUSIONS:Among patients with ESKD on hemodialysis, PPIs and not histamine-2 receptor antagonists were associated with hip fracture events.

SUBMITTER: Vangala C

PROVIDER: S-EPMC6218825 | biostudies-other | 2018 Oct

REPOSITORIES: biostudies-other

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Proton Pump Inhibitors, Histamine-2 Receptor Antagonists, and Hip Fracture Risk among Patients on Hemodialysis.

Vangala Chandan C Niu Jingbo J Lenihan Colin R CR Mitch William E WE Navaneethan Sankar D SD Winkelmayer Wolfgang C WC

Clinical journal of the American Society of Nephrology : CJASN 20180927 10

<h4>Background and objectives</h4>An association between proton pump inhibitor (PPI) use and hip fracture risk has been described in the general population, where the primary causative hypothesis focuses on impaired gastrointestinal calcium absorption. The impact of acid suppressor use on hip fracture risk in a high-risk subset, patients with ESKD requiring hemodialysis, is unknown and could help further distinguish the reason for higher susceptibility among PPI users.<h4>Design, setting, partic ...[more]

PMID: 30262672

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Project description:BackgroundEpidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are increasingly used for advanced non-small cell lung cancer (NSCLC) as first-line therapy. The bioavailability and efficacy of oral EGFR-TKIs could be affected by acid suppression (AS) therapy such as PPIs and H2RAs which are reported to be over-prescribed. Hence, there is a need to investigate the effect of AS on the overall survival (OS), progression-free survival (PFS) and adverse effect profile in patients treated with EGFR TKIs.MethodsAn electronic database search of Medline and Embase was performed following PRISMA guidelines on 17 January 2021. Studies analyzing interactions between EGFR TKIs and PPIs/H2RAs in NSCLC patients were included. Abstracts, non-English or non-Japanese studies or studies using non-EGFR TKIs were excluded. Hazard ratios (HRs) were pooled using generic inverse variance random effects model. Effect sizes for dichotomous variables were pooled using Mantel-Haenszel random effects model. Significance was considered at P≤0.05. Heterogeneity was assessed with Cochran Q-test and I2 test. Publication bias was assessed with funnel plots. The assessment of quality and risk of bias of randomized and non-randomized studies were undertaken with RoB 2 and the ROBINS-I tool respectively.ResultsOut of 1,173 potentially relevant articles, 14 articles were included in the final analysis. The pooled prevalence of AS in patients taking EGFR TKI was 30.71% in 4,010 individuals. Patients who were treated only with EGFR TKI had significantly better OS (HR =1.46, 95% CI: 1.27-1.72; P<0.00001) and PFS (HR =1.63, 95% CI: 1.35-1.98; P<0.00001). The OS for EGFR mutation positive patients only was as similarly significant as the OS in all patients taking EGFR TKI, while the PFS in mutation positive patients was significantly worsened with AS. PPIs resulted in a significantly worsened OS and PFS but H2RAs did not produce significantly different OS and PFS between AS and non-AS users. There were no significant differences in the incidence of rash (OR =0.81, 95% CI: 0.50-1.32; P=0.40), diarrhoea (OR =1.03, 95% CI: 0.63-1.67; P=0.91) or other adverse effects.ConclusionsCo-administration of AS medications with first-generation EGFR-TKIs in NSCLC worsens survival outcomes. Physicians should only prescribe AS medications when absolutely clinically indicated.

Project description:Background:Studies have shown the potential benefit of stress ulcer prophylaxis including histamine-2 receptor antagonists (H2RA) and proton pump inhibitors (PPI) in critically ill patients. However, the adverse effects of stress ulcer prophylaxis such as Clostridioides difficile infection (CDI) and hospital-acquired pneumonia have been reported. Abdominal septic shock is associated with increased risk of bleeding, CDI, and pneumonia; however, which ulcer prophylaxis might be associated with better outcomes in patients with septic shock after lower gastrointestinal tract perforation is unknown. Methods:In this retrospective cohort study using the Japanese Diagnosis Procedure Combination database from July 2010 to March 2015, we identified patients aged 18?years or older who received open abdominal surgery for lower gastrointestinal tract perforation and who used vasopressors and antibiotics within 2?days of admission. We performed propensity score matching and inverse probability of treatment weighting (IPTW) to compare the outcomes between patients who received H2RA and those who received PPI within 2?days of admission. The outcomes included gastrointestinal bleeding requiring endoscopic hemostasis within 28?days of admission, 28-day mortality, CDI, and hospital-acquired pneumonia. Results:The propensity score matching created 1088 pairs of patients who received H2RA or PPI within 2?days of admission. There were no significant differences between the H2RA and PPI groups regarding gastrointestinal bleeding requiring endoscopic hemostasis within 28?days of admission (0.74% vs 1.3%, risk ratio 0.57 (0.24-1.4), and P = 0.284), 28-day mortality (11.3% vs 12.9%, risk ratio 0.88 (0.68-1.1), and P = 0.386), CDI (0.64% vs 0.46%, risk ratio 1.4 (0.45-4.4), and P = 0.774), and hospital-acquired pneumonia (3.0% vs 4.3%, risk ratio 0.70 (0.45-1.1), and P = 0.138). IPTW analysis showed similar results. Conclusions:There were no significant differences in gastrointestinal bleeding requiring endoscopic hemostasis within 28?days of admission, 28-day mortality, CDI, and hospital-acquired pneumonia between H2RA and PPI in patients with septic shock after lower gastrointestinal tract perforation.

Dataset Information

Proton Pump Inhibitors, Histamine-2 Receptor Antagonists, and Hip Fracture Risk among Patients on Hemodialysis.

Publications

Proton Pump Inhibitors, Histamine-2 Receptor Antagonists, and Hip Fracture Risk among Patients on Hemodialysis.

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