Repurposing existing drugs for cardiovascular risk management: a focus on methotrexate

Article Details

Authors
Arduino A Mangoni MD, PhD, FRCP, FRACP, Sara Tommasi PhD, Angelo Zinellu PhD, Salvatore Sotgia MSc, Ciriaco Carru PhD, Matteo Piga MD, Gian Luca Erre MD

Article Type
Review

DOI
10.7573/dic.212557

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Abstract

About 20% of patients with a history of atherosclerotic cardiovascular disease will experience further cardiovascular events despite maximal pharmacological treatment with cardioprotective drugs. This highlights the presence of residual cardiovascular risk in a significant proportion of patients and the need for novel, more effective therapies. These therapies should ideally target different pathophysiological pathways involved in the onset and the progression of atherosclerosis, particularly the inflammatory and immune pathways. Methotrexate is a firstline disease-modifying antirheumatic drug that is widely used for the management of autoimmune and chronic inflammatory disorders. There is some in vitro and in vivo evidence that methotrexate might exert a unique combination of antiinflammatory, blood pressure lowering, and vasculoprotective effects. Pending the results of large prospective studies investigating surrogate end-points as well as morbidity and mortality, repurposing methotrexate for cardiovascular risk management might represent a cost-effective strategy with immediate public health benefits. This review discusses the current challenges in the management of cardiovascular disease; the available evidence on the effects of methotrexate on inflammation, blood pressure, and surrogate markers of arterial function; suggestions for future research directions; and practical considerations with the use of methotrexate in this context.

Keywords: arterial function, atherosclerosis, blood pressure, cardiovascular risk, inflammation, methotrexate, repurposing.

Citation: Mangoni AA, Tommasi S, Zinellu A, Sotgia S, Carru C, Piga M, Erre GL. Repurposing existing drugs for cardiovascular risk management: a focus on methotrexate. Drugs in Context 2018; 7: 212557. DOI: 10.7573/dic.212557

Contributions: AAM wrote the first draft of the article; ST, AZ, SS, CC, MP, and GLR critically reviewed the first and subsequent drafts; AAM wrote the final version of the article. ST, AZ, SS, CC, MP, and GLR reviewed and approved the final version.

Disclosure and potential conflicts of interest: Dr Mangoni reports grants from medac GmbH (Germany), during the conduct of the study. The other authors declare that they had no conflict of interest in preparing this article. The International Committee of Medical Journal Editors (ICMJE) Potential Conflicts of Interests form for the authors are available for download at https://www.drugsincontext.com/wp-content/uploads/2018/10/dic.212557-COI.pdf

Acknowledgments: None.

Funding declaration: There was no funding associated with the preparation of this article.

Copyright: Copyright © 2018 Mangoni AA, Tommasi S, Zinellu A, Sotgia S, Carru C, Piga M, Erre GL. Published by Drugs in Context under Creative Commons License Deed CC BY NC ND 4.0 which allows anyone to copy, distribute, and transmit the article provided it is properly attributed in the manner specified below. No commercial use without permission.

Correct attribution: Copyright © 2018 Mangoni AA, Tommasi S, Zinellu A, Sotgia S, Carru C, Piga M, Erre GL. https://doi.org/10.7573/dic.212557. Published by Drugs in Context under Creative Commons License Deed CC BY NC ND 4.0.

Article URL: https://www.drugsincontext.com/repurposing-existing-drugs-for-cardiovascular-risk-management-a-focus-on-methotrexate

Correspondence: Arduino A Mangoni, Discipline of Clinical Pharmacology, College of Medicine and Public Health, Flinders University and Flinders Medical Centre, Adelaide, Australia. arduino.mangoni@flinders.edu.au

Provenance: invited; externally peer reviewed.

Submitted: 10 September 2018; Peer review comments to author: 15 October 2018; Revised manuscript received: 25 October 2018; Accepted: 26 October 2018; Publication date: 14 November 2018.

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