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Effect of ciclosporin on safety, lymphocyte kinetics and left ventricular remodelling in acute myocardial infarction
Author(s) -
Cormack Suzanne,
Mohammed Ashfaq,
Panahi Pedram,
Das Rajiv,
Steel Alison J.,
Chadwick Thomas,
Bryant Andrew,
Egred Mohaned,
Stellos Konstantinos,
Spyridopoulos Ioakim
Publication year - 2020
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/bcp.14252
Subject(s) - medicine , ciclosporin , myocardial infarction , cardiology , bolus (digestion) , percutaneous coronary intervention , anesthesia , transplantation
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/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)