Sajesh K Veettil1, Saranrat Sadoyu2, Elizabeth M Bald3, Viji P Chandran4, Scott Anh Tuan Khuu3, Panitan Pitak5, Yeong Yeh Lee6,7, Athira Balakrishnan Nair4, Paul T Antony8, Alexander C Ford9,10, Nathorn Chaiyakunapruk1,11. 1. Department of Pharmacotherapy, College of Pharmacy, University of Utah, Salt Lake City, UT, USA. 2. Department of Pharmacy, Pakchongnana Hospital, Pakchong, Thailand. 3. College of Pharmacy, University of Utah, Salt Lake City, UT, USA. 4. Department of Pharmacy Practice, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, India. 5. Clinical Department, Nan Hospital, Nan, Thailand. 6. School of Medical Sciences, Universiti Sains Malaysia, Kota Bharu, Malaysia. 7. GI Function and Motility Unit, Hospital USM, Universiti Sains Malaysia, Kota Bharu, Malaysia. 8. Department of Rheumatology, Amala Institute of Medical Sciences, Kerala, India. 9. Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, UK. 10. Leeds Institute of Medical Research at St. James's, University of Leeds, Leeds, UK. 11. School of Pharmacy, University of Wisconsin, Madison, WI, USA.
Abstract
AIMS: 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.
AIMS: 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.
Authors: Shanna C Trenaman; Austin Harding; Susan K Bowles; Susan A Kirkland; Melissa K Andrew Journal: Front Pharmacol Date: 2022-06-22 Impact factor: 5.988