PMID- 32067256
OWN - NLM
STAT- MEDLINE
DCOM- 20210728
LR  - 20220531
IS  - 1365-2125 (Electronic)
IS  - 0306-5251 (Print)
IS  - 0306-5251 (Linking)
VI  - 86
IP  - 7
DP  - 2020 Jul
TI  - Effect of ciclosporin on safety, lymphocyte kinetics and left ventricular 
      remodelling in acute myocardial infarction.
PG  - 1387-1397
LID - 10.1111/bcp.14252 [doi]
AB  - AIMS: 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/muL, control vs 
      ciclosporin) and increased to 1454 vs 1650 cells/muL 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).
CI  - (c) 2020 The Authors. British Journal of Clinical Pharmacology published by John 
      Wiley & Sons Ltd on behalf of British Pharmacological Society.
FAU - Cormack, Suzanne
AU  - Cormack S
AD  - Freeman Hospital, Newcastle upon Tyne, UK.
AD  - Translational and Clinical Research Institute, Faculty of Medical Sciences, 
      Newcastle University, UK.
FAU - Mohammed, Ashfaq
AU  - Mohammed A
AD  - Freeman Hospital, Newcastle upon Tyne, UK.
FAU - Panahi, Pedram
AU  - Panahi P
AD  - Freeman Hospital, Newcastle upon Tyne, UK.
FAU - Das, Rajiv
AU  - Das R
AD  - Freeman Hospital, Newcastle upon Tyne, UK.
AD  - Faculty of Health and Life Sciences, Northumbria University, UK.
FAU - Steel, Alison J
AU  - Steel AJ
AD  - Newcastle Clinical Trials Unit, Faculty of Medical Sciences, Newcastle 
      University, UK.
FAU - Chadwick, Thomas
AU  - Chadwick T
AD  - Population Health Sciences Institute, Newcastle University, UK.
FAU - Bryant, Andrew
AU  - Bryant A
AD  - Population Health Sciences Institute, Newcastle University, UK.
FAU - Egred, Mohaned
AU  - Egred M
AD  - Freeman Hospital, Newcastle upon Tyne, UK.
FAU - Stellos, Konstantinos
AU  - Stellos K
AD  - Freeman Hospital, Newcastle upon Tyne, UK.
AD  - Translational and Clinical Research Institute, Faculty of Medical Sciences, 
      Newcastle University, UK.
FAU - Spyridopoulos, Ioakim
AU  - Spyridopoulos I
AUID- ORCID: 0000-0002-2750-2444
AD  - Freeman Hospital, Newcastle upon Tyne, UK.
AD  - Translational and Clinical Research Institute, Faculty of Medical Sciences, 
      Newcastle University, UK.
CN  - CAPRI investigators
LA  - eng
SI  - ClinicalTrials.gov/NCT02390674
GR  - FS/12/31/29533/BHF_/British Heart Foundation/United Kingdom
GR  - FS/15/77/31823/BHF_/British Heart Foundation/United Kingdom
GR  - NIHR Newcastle Biomedical Research Centre/International
GR  - PG/18/25/33587/BHF_/British Heart Foundation/United Kingdom
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20200311
PL  - England
TA  - Br J Clin Pharmacol
JT  - British journal of clinical pharmacology
JID - 7503323
RN  - 83HN0GTJ6D (Cyclosporine)
SB  - IM
MH  - *Cyclosporine/therapeutic use
MH  - Double-Blind Method
MH  - Humans
MH  - Kinetics
MH  - Lymphocytes
MH  - Magnetic Resonance Imaging
MH  - *Myocardial Infarction/drug therapy
MH  - Treatment Outcome
MH  - Ventricular Remodeling
PMC - PMC7318996
OTO - NOTNLM
OT  - T-lymphocytes
OT  - acute myocardial infarction
OT  - cardiac MRI
OT  - ciclosporin
OT  - left ventricular function
OT  - reperfusion injury
COIS- There are no competing interests to declare.
EDAT- 2020/02/19 06:00
MHDA- 2021/07/29 06:00
PMCR- 2020/03/11
CRDT- 2020/02/19 06:00
PHST- 2019/07/10 00:00 [received]
PHST- 2019/12/12 00:00 [revised]
PHST- 2019/12/23 00:00 [accepted]
PHST- 2020/02/19 06:00 [pubmed]
PHST- 2021/07/29 06:00 [medline]
PHST- 2020/02/19 06:00 [entrez]
PHST- 2020/03/11 00:00 [pmc-release]
AID - BCP14252 [pii]
AID - 10.1111/bcp.14252 [doi]
PST - ppublish
SO  - Br J Clin Pharmacol. 2020 Jul;86(7):1387-1397. doi: 10.1111/bcp.14252. Epub 2020 
      Mar 11.