Umbrella review of 42 systematic reviews with meta‐analyses: the safety of proton pump inhibitors

Salvo, Elizabeth M.; Ferko, Nicole; Cash, Sarah B.; Gonzalez, Ailish; Kahrilas, Peter J.

doi:10.1111/apt.16407

Cited by 51 publications

(45 citation statements)

References 74 publications

(227 reference statements)

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“…The included articles were published between 2009 and 2021. The descriptive characteristics of T A B L E 1 Criteria for quality of evidence classification in meta-analysis of observational studies [10][11][12][13] Category Criteria…”

Section: Meta-analyses Of Cohort Studiesmentioning

confidence: 99%

Association of proton‐pump inhibitor use with adverse health outcomes: A systematic umbrella review of meta‐analyses of cohort studies and randomised controlled trials

Veettil

Sadoyu²,

Bald

et al. 2021

Brit J Clinical Pharma

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The aim was to perform an umbrella review to summarise the existing evidence on proton-pump inhibitor (PPI) use and adverse outcomes and to grade the certainty of evidence.Methods: Electronic databases were searched up to July 2021 for meta-analyses of cohort studies and/or randomised controlled trials (RCTs). Summary effect sizes from a random-effects model, between-study heterogeneity, 95% prediction interval, small-study effect, excess significance and credibility ceilings were devised to classify the credibility of evidence from meta-analyses of cohort studies, whereas the GRADE approach was used for meta-analyses of RCTs.Results: In meta-analyses of cohort studies, 52 of the 91 examined associations were statistically significant (P ≤ .05). Convincing evidence emerged from main analysis for the association between PPI use and risk of all-site fracture and chronic kidney disease in the elderly population. However, none of these associations remained supported by convincing evidence after sensitivity analyses. The use of PPI is also associated with an increased risk of mortality due to COVID-19 infection and other related adverse outcomes, but the quality of evidence was weak. In meta-analyses of RCTs, 38 of the 63 examined associations were statistically significant. However, no associations were supported by high or moderate-quality evidence.Conclusion: This study's findings imply that most putative adverse outcomes associated with PPI use may not be supported by high-quality evidence and are likely to have been affected by underlying confounding factors. Future research is needed to confirm the causal association between PPI use and risk of fracture and chronic kidney disease.

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Section: Meta-analyses Of Cohort Studiesmentioning

confidence: 99%

Association of proton‐pump inhibitor use with adverse health outcomes: A systematic umbrella review of meta‐analyses of cohort studies and randomised controlled trials

Veettil

Sadoyu²,

Bald

et al. 2021

Brit J Clinical Pharma

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“…There is no increase in PPI acceptance over time (no correlation shown in multivariate analysis) while misuse and adverse effects and drug interactions are increasingly described in the scientific literature [ 1 , 3 – 5 , 8 , 10 , 27 ]. Data from the literature underlined that lack of time and perceiving PPIs as “harmless” affect physicians' decision making [ 29 ].…”

Section: Discussionmentioning

confidence: 99%

“…)-negative peptic ulcer disease, treatment and prophylaxis of NSAID-associated gastric ulcers, and management of gastric acid hypersecretory states [1]. Despite their efficacy, long-term use of PPIs has been linked to several adverse effects [1,[3][4][5].…”

Section: Introductionmentioning

confidence: 99%

Characteristics of Pharmacists’ Interventions Related to Proton-Pump Inhibitors in French Hospitals: An Observational Study

Yailian

Huet

Charpiat

et al. 2022

International Journal of Clinical Practice

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Background/Objective. Overprescribing proton-pump inhibitors (PPIs) has become the norm worldwide and represents a global health issue with tangible clinical and economic consequences. At national level, we do not know how pharmacists are contributing to this issue. Thus, the study focused on analyzing drug-related problems (DRPs) pertaining to PPI prescriptions, detected during the medication order review process in French hospitals, and associated pharmacist interventions (PIs). Methods. The study was based on a retrospective analysis of pharmacist interventions for DRPs detected during the medication order review and documented into the French Act-IP© database over a 12-year period. DRPs and PIs were analyzed, and independent factors of physician acceptance were assessed via multiple logistic regression. Results. Out of the 620,620 PIs registered, 29,694 targeted a PPI (4.8%). PPI’s DRPs were mostly related to the prescription of a “drug not available at the hospital” (26.1%) and a “drug use without indication” (18.3%); PIs were mostly “drug switch” (35.9%) and “drug discontinuation” (26.1%). In all, 18,919 PIs were accepted by physicians (63.7%). Acceptance was significantly associated with patient age: less accepted for the 18–75 years group (OR = 0.59, 95 CI [0.46–0.76]), and the >75 years group (OR = 0.57, 95 CI [0.44–0.73]) vs. <18 years group; for the type of DRP, “drug use without indication” was the less accepted (OR = 0.73, 95 CI [0.63–0.85]); for the type of PI, “dose adjustment” was the less accepted (OR = 0.32, 95 CI [0.23–0.45]). Conclusion. Pharmacists contribute to preventing DRPs associated with PPI prescriptions during the medication order review process. Moreover, they often detect PPIs used without indication and they propose drug discontinuation, which contributes to the PPI deprescribing process. PIs should be further developed in the future to reduce PPI overprescription.

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“…Biological plausibility for the presumed PPI - COVID-19 relationship is based on reduced antiviral resistance due to prolonged gastrointestinal hypochlorhydria and subsequently increased pulmonary colonization [5, 6, 8]. Theoretically, the (presumed) effects on gut microbiome and micronutrient deficiencies [7, 8] might contribute. Two questions about pre-morbid PPI use seem to naturally arise from this mechanistic rationale: one pertaining to the risk of infection and the other one to the risk of severe COVID-19.…”

Section: Introductionmentioning

confidence: 99%

“…Long-term PPI use has been suggested associated with the risk of worsening or incidence of variety of diseased conditions [5, 6]. Two recent comprehensive evaluations demonstrated that quality of evidence relating PPIs as potential causes to these adverse events was “low” or “very low” predominantly for the following reasons: mostly observational data, modest effects commonly burdened by residual confounding, bias by indication, protopathic bias and data inconsistency [2, 7].…”

Section: Introductionmentioning

confidence: 99%

People exposed to proton pump inhibitors shortly preceding COVID-19 diagnosis are not at an increased risk of subsequent hospitalizations and mortality: a nation-wide matched cohort study

Kodvanj

Homolak

Trkulja

2022

Preprint

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BackgroundSeveral studies assessed the effect of pre-morbid exposure to proton pump inhibitors (PPIs) on disease course in adult COVID-19 patients with somewhat inconsistent results.MethodsThis population-based matched cohort study embraced first COVID-19 episodes in adults diagnosed up to August 15 2021 in Croatia. Considering over-the-counter (OTC) availability of PPIs, patients were classified based on exposure to PPIs and burden of PPI-requiring conditions as “non-users” (no issued prescriptions, no recorded treatment-requiring conditions between January 1 2019 and COVID-19 diagnosis), “possible users” (no issued prescriptions, recorded treatment-requiring conditions; OTC use possible) and “users” (different intensity of issued prescriptions over 12 months prior to diagnosis, at least one within 3 months). Subsets were mutually exactly matched in respect to a range of pre-COVID-19 characteristics. The contrast between “users” and “possible users” was considered the most informative for the effect of PPIs that is separate of the effect of PPI-requiring conditions.ResultsAmong 433609 COVID-19 patients, 332389 were PPI “non-users”, 18170 were “possible users”, and 55098 were “users”. Users and possible users were matched 41195 to 17334 and 33272 to 16434 in the primary and sensitivity analyses. There was no relevant difference between “users” and “possible users” regarding COVID-19-related mortality [RR=0.93 (95%CI 0.85-1.02; RD= -0.34% (−0.73, 0.03) in primary and RR=0.88 (0.78-0.98); RD=-0.45 (− 0.80, -0.11) in sensitivity analysis] or COVID-19-related hospitalizations [RR=1.04 (0.97-1.13); RD=0.29% (−0.16, 0.73) in primary and RR=1.05 (0.97-1.15); RD=0.32% (−0.12, 0.75) in sensitivity analysis].ConclusionsPre-morbid exposure to PPIs does not affect the risk of death or hospitalization in adult COVID-19 patients.

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Umbrella review of 42 systematic reviews with meta‐analyses: the safety of proton pump inhibitors

Cited by 51 publications

References 74 publications

Association of proton‐pump inhibitor use with adverse health outcomes: A systematic umbrella review of meta‐analyses of cohort studies and randomised controlled trials

Association of proton‐pump inhibitor use with adverse health outcomes: A systematic umbrella review of meta‐analyses of cohort studies and randomised controlled trials

Characteristics of Pharmacists’ Interventions Related to Proton-Pump Inhibitors in French Hospitals: An Observational Study

People exposed to proton pump inhibitors shortly preceding COVID-19 diagnosis are not at an increased risk of subsequent hospitalizations and mortality: a nation-wide matched cohort study

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