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Adverse outcomes of long-term use of proton pump inhibitors

a systematic review and meta-analysis

Islam, Md.Mohaimenula,b; Poly, Tahmina N.a,b; Walther, Bruno A.c; Dubey, Navneet K.d; Anggraini Ningrum, Dina N.a,b,e; Shabbir, Syed-Abdula,b; (Jack) Li, Yu-Chuana,b

European Journal of Gastroenterology & Hepatology: December 2018 - Volume 30 - Issue 12 - p 1395–1405
doi: 10.1097/MEG.0000000000001198
Review Articles

The association between the long-term use of proton pump inhibitors (PPIs) and the risks of various diseases remains controversial. Therefore, the primary objective of this study was to quantify the associations as presented in the literature and to also provide this information to healthcare professionals and patients about their potentially adverse effects. In July 2016, we searched through Medline (PubMed), Embase, and the Cochrane Library from inception using common keywords. We included observational studies that provided risk estimates on the long-term use of PPIs and their adverse effects. Overall, 43 studies were included in the systematic review, of which 28 studies were also included in the random effect meta-analysis. Odds of community-acquired pneumonia, hip fracture, and colorectal cancer were 67% [odds ratio (OR)=1.67; 95% confidence interval (CI): 1.04–2.67], 42% (OR=1.42; 95% CI: 1.33–1.53), and 55% (OR=1.55; 95% CI: 0.88–2.73) higher in patients with long-term PPIs use compared with patients who did not use PPIs. Although the use of PPIs provides short-term health benefits, their prolonged use is associated with minor and also potentially major adverse health outcomes. Hence, we strongly recommend that the prescription of PPIs should be done with caution to improve the medication’s efficacy and patients’ safety.

aGraduate Institute of Biomedical Informatics, College of Medical Science and Technology

bInternational Center for Health Information Technology (ICHIT)

cMaster Program in Global Health and Development, College of Public Health

dGraduate Institute of Biomedical Materials and Tissue Engineering, Taipei Medical University, Taipei, Taiwan

ePublic Health Department, Universitas Negeri Semarang, Semarang, Indonesia

Correspondence to Yu-Chuan (Jack) Li, MD, PhD, Graduate Institute of Biomedical Informatics, College of Medical Science and Technology, Taipei Medical University, 250 Wu-Hsing Street, Taipei 110, Taiwan Tel: +886 227 361 661 x7600; fax: +886 266 387 537; e-mails:,

Received February 18, 2018

Accepted May 8, 2018

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