Proton Pump Inhibitors and Risk of Fracture: A Systematic Review and Meta-Analysis of Observational Studies

Introduction: Proton Pump Inhibitors (PPIs) are generally considered safe, but recent evidence suggests otherwise. Objective: This systematic review and meta-analysis assessed the association between PPIs and the risk of myocardial infarction (MI), using both clinical trials and observational studies. Methods: A systematic search was performed in December 2019 to retrieve all potential studies using PubMed, PsycInfo, International Pharmaceutical Abstracts, Web of Science, and Clinicaltrials.gov. This search initially identified any published studies describing any adverse event (AE) or outcomes related to PPI. Records were included in this study if 1) studies were published in English, 2) study design was clinical trials or observational studies, 3) PPI use was the exposure or treatment, and 4) study outcome was the incidence of MI. Two researchers independently reviewed all identified records, performed full article review, extracted data into structured evidence table, and conducted quality assessment using Newcastle-Ottawa Scale and Quality Assessment Tool for Quantitative Studies. Meta-analysis was performed using the RStudio software to assess the risk of MI with PPI use. Results: A total of 4,507 abstracts meeting the inclusion criteria were identified, and 20 full articles were included in this study, among which 10 were cohort, 3 were case-control, 3 were RCT post-hoc analysis, and 4 were RCT studies. The pooled Odds Ratio (OR)=1.40 with 95% CI=1.20-1.63 for all studies indicated the presence of an association between PPI use and increased risk of MI compared to PPI non-users. Meta-analysis found a similar association between PPI use and increased risk of MI in observational studies (OR=1.40; 95% CI=1.20, 1.64) but no association (OR=0.90; 95% CI=0.47, 1.73) in RCT-studies. Heterogeneity was high (I 2 > 75%) for all analyses except for RCTs (I 2 =0%). Conclusion: Although our meta-analysis identified the association between PPI use and increased risk of MI, results from RCTs did not agree with observational studies. Due to the mixed findings by study designs and high variation of heterogeneity among studies, the pharmacovigilance system should evaluate different levels of evidence to support decision making in safety of drug products.

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Proton pump inhibitors linked to hypomagnesemia: a systematic review and meta-analysis of observational studies

Renal Failure ◽

10.3109/0886022x.2015.1057800 ◽

2015 ◽

Vol 37 (7) ◽

pp. 1237-1241 ◽

Cited By ~ 78

Author(s):

Wisit Cheungpasitporn ◽

Charat Thongprayoon ◽

Wonngarm Kittanamongkolchai ◽

Narat Srivali ◽

Peter J. Edmonds ◽

...

Keyword(s):

Systematic Review ◽

Proton Pump Inhibitors ◽

Proton Pump ◽

Observational Studies ◽

Meta Analysis

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Meta-analysis of proton pump inhibitors induced risk of community-acquired pneumonia

International Journal for Quality in Health Care ◽

10.1093/intqhc/mzaa041 ◽

2020 ◽

Vol 32 (5) ◽

pp. 292-299 ◽

Cited By ~ 2

Author(s):

Phung Anh Nguyen ◽

Mohaimenul Islam ◽

Cooper J Galvin ◽

Chih-Cheng Chang ◽

Soo Yeon An ◽

...

Keyword(s):

Systematic Review ◽

Random Effects ◽

Proton Pump Inhibitors ◽

Proton Pump ◽

Observational Studies ◽

Meta Analysis ◽

Community Acquired Pneumonia ◽

Cochrane Library ◽

High Dose ◽

Increased Risk

Abstract Purpose Proton pump inhibitors (PPIs), one of the most widely used medications, are commonly used to suppress several acid-related upper gastrointestinal disorders. Acid-suppressing medication use could be associated with increased risk of community-acquired pneumonia (CAP), although the results of clinical studies have been conflicting. Data sources A comprehensive search of MEDLINE, EMBASE and Cochrane library and Database of Systematic Reviews from the earliest available online year of indexing up to October 2018. Study selection We performed a systematic review and meta-analysis of observational studies to evaluate the risk of PPI use on CAP outcomes. Data extraction Included study location, design, population, the prevalence of CAP, comparison group and other confounders. We calculated pooled odds ratio (OR) using a random-effects meta-analysis. Results of data synthesis Of the 2577 studies screening, 11 papers were included in the systematic review and 7 studies with 65 590 CAP cases were included in the random-effects meta-analysis. In current PPI users, pooled OR for CAP was 1.86 (95% confidence interval (CI), 1.30–2.66), and in the case of recent users, OR for CAP was 1.66 (95% CI, 1.22–2.25). In the subgroup analysis of CAP, significance association is also observed in both high-dose and low-dose PPI therapy. When stratified by duration of exposure, 3–6 months PPIs users group was associated with increased risk of developing CAP (OR, 2.05; 95% CI, 1.22–3.45). There was a statistically significant association between the PPI users and the rate of hospitalization (OR, 2.59; 95% CI, 1.83–3.66). Conclusion We found possible evidence linking PPI use to an increased risk of CAP. More randomized controlled studies are warranted to clarify an understanding of the association between PPI use and risk of CAP because observational studies cannot clarify whether the observed epidemiologic association is a causal effect or a result of unmeasured/residual confounding.

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