proton pump inhibitors

All cause mortality and cause specific mortality associated with taking PPIs (values reported as number of attributable deaths per 1000 patients taking PPIs).

RESULTS:

There were 45.20 excess deaths (95% confidence interval 28.20 to 61.40) per 1000 patients taking PPIs. Circulatory system diseases (number of attributable deaths per 1000 patients taking PPIs 17.47, 95% confidence interval 5.47 to 28.80), neoplasms (12.94, 1.24 to 24.28), infectious and parasitic diseases (4.20, 1.57 to 7.02), and genitourinary system diseases (6.25, 3.22 to 9.24) were associated with taking PPIs. There was a graded relation between cumulative duration of PPI exposure and the risk of all cause mortality and death due to circulatory system diseases, neoplasms, and genitourinary system diseases. Analyses of subcauses of death suggested that taking PPIs was associated with an excess mortality due to cardiovascular disease (15.48, 5.02 to 25.19) and chronic kidney disease (4.19, 1.56 to 6.58). Among patients without documented indication for acid suppression drugs (n=116 377), taking PPIs was associated with an excess mortality due to cardiovascular disease (22.91, 11.89 to 33.57), chronic kidney disease (4.74, 1.53 to 8.05), and upper gastrointestinal cancer (3.12, 0.91 to 5.44). Formal interaction analyses suggested that the risk of death due to these subcauses was not modified by a history of cardiovascular disease, chronic kidney disease, or upper gastrointestinal cancer. Taking PPIs was not associated with an excess burden of transportation related mortality and death due to peptic ulcer disease (as negative outcome controls).

CONCLUSIONS:

Taking PPIs is associated with a small excess of cause specific mortality including death due to cardiovascular disease, chronic kidney disease, and upper gastrointestinal cancer. The burden was also observed in patients without an indication for PPI use. Heightened vigilance in the use of PPI may be warranted.

Author/s:

Xie, Y, Bowe, B, Yan, Y, Xian, H, Li, T, Al-Aly, Z

Proton Pump Inhibitor Use and Risk of Chronic Kidney Disease

Tracy Ashby — Mon, 11 Mar 2019 05:00:00 +0000

Date Added:

March 11, 2019

Journal/Publication:

JAMA Internal Medicine

Publisher:

American Medical Association

Publication Date:

February 1, 2017

Issue:

Volume:

176

Pages:

238-246

URL:

Proton Pump Inhibitor Use and Risk of Chronic Kidney Disease

Type:

Clinical Research Results

Format:

Article

DOI (1):

10.1001/jamainternmed.2015.7193

Keywords

proton pump inhibitors

chronic kidney disease

interstitial nephritis

PMID (1):

26752337

MeSH

proton pump inhibitors

nephritis, interstitial

renal insufficiency, chronic

Glomerular Filtration Rate

PPIs appear to be associated with both acute (interstitial nephritis) and chronic kidney problems. While this is an epidemiological study, proving association not causation, it may be the best evidence we will be able to get.

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Context

Proton pump inhibitors (PPIs) are among the most commonly used drugs worldwide, and have been linked to acute interstitial nephritis. Less is known about the relationship between PPI use and chronic kidney disease (CKD).

Objective

To quantify the association between PPI use and incident CKD in a population-based cohort.

Design, Setting and Participants

10,482 participants in the Atherosclerosis Risk in Communities (ARIC) study with an estimated glomerular filtration rate (eGFR) of ≥60mL/min/1.73m2 were followed from a baseline visit (1996–1999) to December 31, 2011. Findings were replicated in an administrative cohort of 248,751 patients with eGFR ≥60mL/min/1.73m2 from Geisinger Health System.

Exposure

Self-reported PPI use in ARIC, or an outpatient PPI prescription in the replication cohort. Histamine-2 receptor (H2) antagonist use was considered a negative control and active comparator.

Main Outcome Measure

Incident CKD, using diagnostic codes indicating CKD at hospital discharge or death. In the replication cohort, incident CKD was defined by outpatient eGFR <60 mL/min/1.73 m2.

Results

Compared to non-users, PPI-users were more often white, obese, and taking antihypertensive medication. In ARIC, PPI use was associated with incident CKD in unadjusted analysis (hazard ratio [HR], 1.45; 95% confidence interval [CI], 1.11–1.90), analysis adjusted for demographic, socioeconomic, and clinical parameters (HR, 1.50; 95% CI, 1.14–1.96), and in analysis with PPI ever-use modeled as a time-varying variable (adjusted HR, 1.35; 95% CI, 1.17–1.55). The association persisted when baseline PPI users were compared directly to H2-antagonist users (adjusted HR, 1.39; 95% CI, 1.01–1.91), and to propensity-score matched non-users (HR, 1.76; 95% CI, 1.13–2.74). In the replication cohort, PPI use was associated with CKD in all analyses, including a time-varying new user design (adjusted HR 1.24; 95% CI, 1.20–1.28). Twice-daily PPI dosing was associated with a higher risk (adjusted HR, 1.46; 95% CI, 1.28–1.67) than once-daily dosing (adjusted HR, 1.15; 95% CI, 1.09–1.21).

Conclusions

PPI use is associated with a 20%–50% higher risk of incident CKD. Future research should evaluate whether limiting PPI use reduces the incidence of CKD.

Author/s:

Lazarus, Benjamin, Chen, Yuan, Wilson, Francis P., Sang, Yingying, Chang, Alex R., Coresh, Josef, Grams, Morgan E.

Proton‐Pump Inhibitors and Long‐Term Risk of Community‐Acquired Pneumonia in Older Adults

Tracy Ashby — Mon, 11 Mar 2019 05:00:00 +0000

Date Added:

March 11, 2019

Journal/Publication:

Journal of the American Geriatrics Society

Publisher:

American Geriatrics Society

Publication Date:

April 20, 2018

Issue:

Volume:

Pages:

1332-1338

URL:

Proton-Pump Inhibitors and Long-Term Risk of Community-Acquired Pneumonia in Older Adults

Type:

Clinical Research Results

Format:

Article

DOI (1):

10.1111/jgs.15385

Keywords

pneumonia

primary care

proton pump inhibitors

PMID (1):

PMC6099478

MeSH

proton pump inhibitors

pneumonia

primary health care

More epidemiological evidence linking PPI use to incident pneumonia in older patients. An association has also been established in patients with COPD

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Objectives

To estimate associations between long‐term use of proton pump inhibitors (PPIs) and pneumonia incidence in older adults in primary care.

Design

Longitudinal analyses of electronic medical records.

Setting

England

Participants

Individuals aged 60 and older in primary care receiving PPIs for 1 year or longer (N=75,050) and age‐ and sex‐matched controls (N=75,050).

Measurements

Net hazard ratios for pneumonia incidence in Year 2 of treatment were estimated using the prior event rate ratio (PERR), which adjusts for pneumonia incidence differences before initiation of treatment. Inverse probability weighted models adjusted for 78 demographic, disease, medication, and healthcare usage measures.

Results

During the second year after initiating treatment, PPIs were associated with greater hazard of incident pneumonia (PERR‐adjusted hazard ratio=1.82, 95% confidence interval=1.27–2.54), accounting for pretreatment pneumonia rates. Estimates were similar across age and comorbidity subgroups. Similar results were also obtained from propensity score– and inverse probability–weighted models.

Conclusion

In a large cohort of older adults in primary care, PPI prescription was associated with greater risk of pneumonia in the second year of treatment. Results were robust across alternative analysis approaches. Controversies about the validity of reported short‐term harms of PPIs should not divert attention from potential long‐term effects of PPI prescriptions on older adults.

Author/s:

Zirk-Sadowski, Jan, Masoli, Jane A., Delgada, Joao, Hamilton, Willie, Strain, W. David, Henley, William, Melzer, David, Ble, Alessandro