TY - JOUR
T1 - Umbrella review of 42 systematic reviews with meta-analyses
T2 - the safety of proton pump inhibitors
AU - Salvo, Elizabeth M.
AU - Ferko, Nicole C.
AU - Cash, Sarah B.
AU - Gonzalez, Ailish
AU - Kahrilas, Peter J.
N1 - Funding Information:
The preparation of this manuscript was funded by Ethicon Inc. The authors thank Anuprita Patkar and Samantha Craigie for their assistance in the development of the final version of this manuscript. Declaration of personal interests: Dr Peter J. Kahrilas has served on advisory boards for Ironwoord Pharmaceuticals and Reckitt Benckiser, and has received research funding from Ironwoord Pharmaceuticals. Ailish Gonzalez is an employee and shareholder of Johnson & Johnson. Elizabeth M. Salvo, Nicole C. Ferko and Sarah B. Cash are employees of EVERSANA. Declaration of funding interests: This study, the writing, and preparation of this paper was funded in full by Ethicon Inc. Data analyses and writing were undertaken by Elizabeth M. Salvo, Nicole C. Ferko, and Sarah B. Cash, who are employees of EVERSANA and received funding from Ethicon Inc. Dr Peter J. Kahrilas was not compensated for his involvement.
Funding Information:
: Dr Peter J. Kahrilas has served on advisory boards for Ironwoord Pharmaceuticals and Reckitt Benckiser, and has received research funding from Ironwoord Pharmaceuticals. Ailish Gonzalez is an employee and shareholder of Johnson & Johnson. Elizabeth M. Salvo, Nicole C. Ferko and Sarah B. Cash are employees of EVERSANA. Declaration of personal interests
Funding Information:
The preparation of this manuscript was funded by Ethicon Inc.
Publisher Copyright:
© 2021 John Wiley & Sons Ltd
PY - 2021/7
Y1 - 2021/7
N2 - Background: Proton pump inhibitors (PPIs) are widely used to treat and prevent acid-related disorders. Despite high efficacy, PPI safety has been increasingly scrutinised. However, no comprehensive review summarising investigations of various adverse events is available. Aims: To perform an umbrella review to comprehensively assess associations between adverse events and PPI use. Methods: In accordance with PRISMA, an umbrella review of systematic reviews with meta-analyses was conducted. PubMed and EMBASE were searched from 2015 to July 2019. AMSTAR 2 and GRADE were used to assess quality and certainty of evidence. Author-reported quality assessments were also reviewed. Results: Forty-two systematic reviews with meta-analyses, supported predominantly by observational evidence, were included. The most comprehensive studies reported statistically significant associations with PPI use for several outcomes, including: fractures (eg, hip; RR = 1.20; 95% CI = 1.14-1.28; n = 2 103 800), kidney disease (eg, acute kidney injury; RR = 1.61; 95% CI = 1.16-2.22; n = 2 396 640), infections (eg, Clostridioides difficile; OR = 1.99; 95% CI = 1.73-2.30; n = 356 683), gastric cancer (OR = 2.50; 95% CI = 1.74-3.85; n = 943 070) and gastrointestinal events (eg, fundic gland polyps; OR = 2.46; 95% CI = 1.42-4.27; n = 40 218). No associations with non-gastric cancers, or neurological disease were concluded, with conflicting evidence for cardiovascular outcomes. Certainty based on GRADE was very low for most outcomes. Conclusions: This review identified several published associations between PPIs and adverse outcomes, however, further investigation is needed to understand their clinical significance and the likelihood of causal relationship. If higher quality evidence is generated substantiating the potential risks, it may be necessary for clinicians to consider alternative treatment strategies, especially when PPI efficacy is suboptimal.
AB - Background: Proton pump inhibitors (PPIs) are widely used to treat and prevent acid-related disorders. Despite high efficacy, PPI safety has been increasingly scrutinised. However, no comprehensive review summarising investigations of various adverse events is available. Aims: To perform an umbrella review to comprehensively assess associations between adverse events and PPI use. Methods: In accordance with PRISMA, an umbrella review of systematic reviews with meta-analyses was conducted. PubMed and EMBASE were searched from 2015 to July 2019. AMSTAR 2 and GRADE were used to assess quality and certainty of evidence. Author-reported quality assessments were also reviewed. Results: Forty-two systematic reviews with meta-analyses, supported predominantly by observational evidence, were included. The most comprehensive studies reported statistically significant associations with PPI use for several outcomes, including: fractures (eg, hip; RR = 1.20; 95% CI = 1.14-1.28; n = 2 103 800), kidney disease (eg, acute kidney injury; RR = 1.61; 95% CI = 1.16-2.22; n = 2 396 640), infections (eg, Clostridioides difficile; OR = 1.99; 95% CI = 1.73-2.30; n = 356 683), gastric cancer (OR = 2.50; 95% CI = 1.74-3.85; n = 943 070) and gastrointestinal events (eg, fundic gland polyps; OR = 2.46; 95% CI = 1.42-4.27; n = 40 218). No associations with non-gastric cancers, or neurological disease were concluded, with conflicting evidence for cardiovascular outcomes. Certainty based on GRADE was very low for most outcomes. Conclusions: This review identified several published associations between PPIs and adverse outcomes, however, further investigation is needed to understand their clinical significance and the likelihood of causal relationship. If higher quality evidence is generated substantiating the potential risks, it may be necessary for clinicians to consider alternative treatment strategies, especially when PPI efficacy is suboptimal.
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U2 - 10.1111/apt.16407
DO - 10.1111/apt.16407
M3 - Review article
C2 - 34114655
AN - SCOPUS:85107555391
SN - 0269-2813
VL - 54
SP - 129
EP - 143
JO - Alimentary Pharmacology and Therapeutics
JF - Alimentary Pharmacology and Therapeutics
IS - 2
ER -
