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Effect of ciclosporin on safety, lymphocyte kinetics and left ventricular remodelling in acute myocardial infarction

Lookup NU author(s): Dr Suzanne Cormack, Dr Alison Steel, Dr Thomas Chadwick, Andrew Bryant, Dr Mohaned Egred, Professor Konstantinos Stellos, Professor Ioakim Spyridopoulos

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

© 2020 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological SocietyAims: Following a favourable pilot trial using a single bolus of ciclosporin, it has been unclear why 2 large studies (CYCLE and CIRCUS) failed to prevent reperfusion injury and reduce infarct size in STEMI (ST elevation myocardial infarction). The purpose of this study was to assess the effect of ciclosporin on myocardial injury, left ventricular remodelling and lymphocyte kinetics in patients with acute STEMI undergoing primary percutaneous coronary intervention. Methods: In this double-blind, single centre trial, we randomly assigned 52 acute STEMI patients with an onset of pain of <6 hours and blocked culprit artery to a single bolus of ciclosporin (n = 26) or placebo (n = 26, control group) prior to reperfusion by stent percutaneous coronary intervention. The primary endpoint was infarct size at 12 weeks. Results: Mean infarct size at 12 weeks was identical in both groups (9.1% [standard deviation= 7.0] vs 9.1% [standard deviation = 7.0], P =.99; 95% confidence interval for difference: −4.0 to 4.1). CD3 T-lymphocytes dropped to similar levels at 90 minutes (867 vs 852 cells/μL, control vs ciclosporin) and increased to 1454 vs 1650 cells/μL at 24 hours. Conclusion: In our pilot trial, a single ciclosporin bolus did not affect infarct size or left ventricular remodelling, matching the results from CYCLE and CIRCUS. Our study suggests that ciclosporin does either not reach ischaemic cardiomyocytes, or requires earlier application during first medical contact. Finally, 1 bolus of ciclosporin is not sufficient to inhibit CD4 T-lymphocyte proliferation during remodelling. We therefore believe that further studies are warranted. (Evaluating the effectiveness of intravenous Ciclosporin on reducing reperfusion injury in pAtients undergoing PRImary percutaneous coronary intervention [CAPRI]; NCT02390674).


Publication metadata

Author(s): Cormack S, Mohammed A, Panahi P, Das R, Steel AJ, Chadwick T, Bryant A, Egred M, Stellos K, Spyridopoulos I

Publication type: Article

Publication status: Published

Journal: British Journal of Clinical Pharmacology

Year: 2020

Pages: epub ahead of print

Online publication date: 17/02/2020

Acceptance date: 23/12/2019

Date deposited: 25/03/2020

ISSN (print): 0306-5251

ISSN (electronic): 1365-2125

Publisher: Blackwell Publishing Ltd

URL: https://doi.org/10.1111/bcp.14252

DOI: 10.1111/bcp.14252

PubMed id: 32067256


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