Volume 37, Issue 6 pp. 1139-1152
ORIGINAL ARTICLE

Heterogeneity in protocols and outcomes to study the effect of renin-angiotensin system blockers in inflammatory bowel disease: A systematic review

Mariana Ferreira-Duarte

Mariana Ferreira-Duarte

Laboratory of Pharmacology, Department of Drug Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal

LAQV@REQUIMTE, University of Porto, Porto, Portugal

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Fernanda S. Tonin

Fernanda S. Tonin

ESTeSL-Escola Superior de Tecnologia da Saúde, Instituto Politécnico de Lisboa, Lisbon, Portugal

H&TRC-Health and Technology Research Center, Instituto Politécnico de Lisboa, Lisbon, Portugal

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Margarida Duarte-Araújo

Margarida Duarte-Araújo

LAQV@REQUIMTE, University of Porto, Porto, Portugal

Department of Immuno-Physiology and Pharmacology, School of Medicine and Biomedical Sciences (ICBAS), University of Porto, Porto, Portugal

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Fernando Fernandez-Llimos

Corresponding Author

Fernando Fernandez-Llimos

Laboratory of Pharmacology, Department of Drug Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal

UCIBIO i4HB - Applied Molecular Biosciences Unit, Faculty of Pharmacy, University of Porto, Porto, Portugal

Correspondence

Fernando Fernandez-Llimos, UCIBIO i4HB - Applied Molecular Biosciences Unit, Faculty of Pharmacy, University of Porto, Rua Jorge de Viterbo Ferreira 228, 4050-313 Porto, Portugal.

Email: [email protected]

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Manuela Morato

Manuela Morato

Laboratory of Pharmacology, Department of Drug Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal

LAQV@REQUIMTE, University of Porto, Porto, Portugal

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First published: 02 July 2023

Funding information: This work was supported by Fundação para a Ciência e Tecnologia (FCT) (Partnership Agreement UIDB-50006/2020 and SFRH/D/145654/2019 to M.F.D.).

Abstract

Background

The renin-angiotensin system (RAS) has been associated with inflammatory bowel disease (IBD), supporting translational relevance of RAS blockers. Comparability of study design/outcomes is fundamental for data analysis/discussion.

Objectives

We aimed at evaluating the heterogeneity among protocols and outcomes to study the effect of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers in IBD.

Methods

This study was performed and reported in accordance with the Cochrane recommendations and PRISMA (PROSPERO-CRD42022323853). Systematic searches were performed in PubMed, Scopus and Web of Science. Studies that met the inclusion criteria were selected. Quality assessment of the studies was done with the SYRCLES's risk of bias tools for animal studies.

Results

Thirty-five pre-clinical studies and six clinical studies were included. Chemical induction of colitis was the most used model, but variable doses of the induction agent were reported. All studies reported at least a disease activity index, a macroscopic score, or a histologic assessment, but these scores were methodologically heterogeneous and reported for different characteristics. Great heterogeneity was also found in drug interventions. Inflammatory markers assessed as outcomes were different across studies.

Conclusion

Lack of standardization of protocols and outcomes among studies threatens the evidence on how RAS blockers influence IBD outcomes.

CONFLICT OF INTEREST STATEMENT

The authors have no conflict of interest to declare.

DATA AVAILABILITY STATEMENT

The data underlying this article are available in the article and in its online supplementary material.

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