Effect of ciclosporin on safety, lymphocyte kinetics and left ventricular remodelling in acute myocardial infarction.
T-lymphocytes
acute myocardial infarction
cardiac MRI
ciclosporin
left ventricular function
reperfusion injury
Journal
British journal of clinical pharmacology
ISSN: 1365-2125
Titre abrégé: Br J Clin Pharmacol
Pays: England
ID NLM: 7503323
Informations de publication
Date de publication:
07 2020
07 2020
Historique:
received:
10
07
2019
revised:
12
12
2019
accepted:
23
12
2019
pubmed:
19
2
2020
medline:
29
7
2021
entrez:
19
2
2020
Statut:
ppublish
Résumé
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. 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. 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. 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).
Identifiants
pubmed: 32067256
doi: 10.1111/bcp.14252
pmc: PMC7318996
doi:
Substances chimiques
Cyclosporine
83HN0GTJ6D
Banques de données
ClinicalTrials.gov
['NCT02390674']
Types de publication
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1387-1397Subventions
Organisme : British Heart Foundation
ID : FS/12/31/29533
Pays : United Kingdom
Organisme : British Heart Foundation
ID : FS/15/77/31823
Pays : United Kingdom
Organisme : NIHR Newcastle Biomedical Research Centre
Pays : International
Organisme : British Heart Foundation
ID : PG/18/25/33587
Pays : United Kingdom
Informations de copyright
© 2020 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.
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