Cyclosporine before PCI in Patients with Acute Myocardial Infarction.

By T. Cung, O. Morel, G. Cayla, G. Rioufol, D. Garcia-Dorado, D. Angoulvant, E. Bonnefoy-cudraz, P. Guérin, M. Elbaz, N. Delarche and 43 more. New England Journal of Medicine, 2015

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BACKGROUND Experimental and clinical evidence suggests that cyclosporine may attenuate reperfusion injury and reduce myocardial infarct size. We aimed to test whether cyclosporine would improve clinical outcomes and prevent adverse left ventricular remodeling. METHODS In a multicenter, double-blind, randomized trial, we assigned 970 patients with an acute anterior ST-segment elevation myocardial infarction (STEMI) who were undergoing percutaneous coronary intervention (PCI) within 12 hours after symptom onset and who had complete occlusion of the culprit coronary artery to receive a bolus injection of cyclosporine (administered intravenously at a dose of 2.5 mg per kilogram of body weight) or matching placebo before coronary recanalization. The primary outcome was a composite of death from any cause, worsening of heart failure during the initial hospitalization, rehospitalization for heart failure, or adverse left ventricular remodeling at 1 year. Adverse left ventricular remodeling was defined as an increase of 15% or more in the left ventricular end-diastolic volume. RESULTS A total of 395 patients in the cyclosporine group and 396 in the placebo group received the assigned study drug and had data that could be evaluated for the primary outcome at 1 year. The rate of the primary outcome was 59.0% in the cyclosporine group and 58.1% in the control group (odds ratio, 1.04; 95% confidence interval [CI], 0.78 to 1.39; P=0.77). Cyclosporine did not reduce the incidence of the separate clinical components of the primary outcome or other events, including recurrent infarction, unstable angina, and stroke. No significant difference in the safety profile was observed between the two treatment groups. CONCLUSIONS In patients with anterior STEMI who had been referred for primary PCI, intravenous cyclosporine did not result in better clinical outcomes than those with placebo and did not prevent adverse left ventricular remodeling at 1 year. (Funded by the French Ministry of Health and NeuroVive Pharmaceutical; CIRCUS ClinicalTrials.gov number, NCT01502774; EudraCT number, 2009-013713-99.).

Subfields: Cardiology and Cardiovascular Medicine, Pathology and Forensic Medicine, Surgery

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Citations in the corpus

Inflammation following acute myocardial infarction: Multiple players, dynamic roles, and novel therapeutic opportunities (2018, background): “As such, the mortality and morbidity following AMI remain significant with 7%mortality and 22% death at one year, respectively (Cung et al., 2015).”
Multitarget Strategies to Reduce Myocardial Ischemia/Reperfusion Injury: JACC Review Topic of the Week. (2019, methodology): “, in the CIRCUS [Cyclosporine and Prognosis in Acute Myocardial Infarction (MI) Patients] trial on cyclosporine A [52]).”
The pathophysiology of acute myocardial infarction and strategies of protection beyond reperfusion: a continual challenge. (2016, background): “The most disappointing lack of translation relates to cyclosporine A which in a pilot phase II trial had reduced infarct size in patients with STEMI undergoing PPCI,(194) but failed to reduce infarct size and improve clinical outcome in two recent larger phase III trials (CIRCUS, CYCLE).(195,196) Th”
Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018 (2018, background): “Over the past two decades tremendous efforts have been dedicated to the development of cytoprotective strategies aimed at interrupting RCD signaling after the initiation of the process (a clinically relevant scenario for most ischemic disorders) [1044, 1045], with relatively deceiving results (despi”