Key result
Ciclosporin fails to reduce infarct size at 12 weeks vs. placebo in acute STEMI.
Why the study?
Following a favourable pilot trial using a single bolus of ciclosporin, it was unclear why two large studies failed to prevent reperfusion injury and reduce infarct size in STEMI.
Does a single bolus of ciclosporin reduce infarct size in acute STEMI patients undergoing primary percutaneous coronary intervention?
RCT (n=52)
Double-blind
randomly assigned
No
Does a single bolus of ciclosporin reduce infarct size in acute STEMI patients undergoing primary percutaneous coronary intervention?
Mean Difference: 0 (95% CI -4–4.1)
Absolute Event Rate: 9.1% vs 9.1%
p-value: p=.99
A single bolus of ciclosporin prior to primary PCI in acute STEMI patients does not reduce infarct size or affect left ventricular remodeling, confirming findings from previous large trials.
No support for pre-reperfusion ciclosporin in STEMI; challenges prior cardioprotection signals and discourages further trials.
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).
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Cormack et al. (2020) conducted an RCT in acute STEMI (n=52). ciclosporin vs. placebo was evaluated on infarct size at 12 weeks (MD 0, 95% CI -4.0 to 4.1, p=.99). A single bolus of ciclosporin prior to reperfusion did not reduce mean infarct size at 12 weeks compared to placebo in patients with acute STEMI (9.1% vs 9.1%; P=0.99).
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