• Nathan Mewton, Thien T Cung, Olivier Morel, Guillaume Cayla, Eric Bonnefoy-Cudraz, Gilles Rioufol, Denis Angoulvant, Patrice Guerin, Meyer Elbaz, Nicolas Delarche, Pierre Coste, Gerald Vanzetto, Marc Metge, Jean-François Aupetit, Bernard Jouve, Pascal Motreff, Christophe Tron, Jean-Noël Labeque, Pierre G Steg, Yves Cottin, Grégoire Range, Jerome Clerc, Patrick Coussement, Fabrice Prunier, Frederique Moulin, Olivier Roth, Loic Belle, Phillipe Dubois, Paul Barragan, Martine Gilard, Christophe Piot, Patrice Colin, Marie-Claude Morice, Jean-Pierre Monassier, Omar Ider, Jean Luc P Dubois-Randé, Thierry Unterseeh, Hervé Lebreton, Thierry Beard, Didier Blanchard, Gilles Grollier, Vincent Malquarti, Patrick Staat, Arnaud Sudre, Magnus J Hansson, Eskil Elmer, Inesse Boussaha, Claire Jossan, Anna Torner, Marc Claeys, David Garcia-Dorado, Michel Ovize, and CIRCUS Study Investigators.
• Hopital Cadiovasculaire Louis Pradel, Clinical Investigation Center, Hospices Civils de Lyon, Lyon,France.
• Am. Heart J. 2015 Jun 1;169(6):758-766.e6.

BackgroundBoth acute myocardial ischemia and reperfusion contribute to cardiomyocyte death in ST-elevation myocardial infarction (STEMI). The final infarct size is the principal determinant of subsequent clinical outcome in STEMI patients. In a proof-of-concept phase II trial, the administration of cyclosporine prior to primary percutaneous coronary intervention (PPCI) has been associated with a reduction of infarct size in STEMI patients.MethodsCIRCUS is an international, prospective, multicenter, randomized, double-blinded, placebo-controlled trial. The study is designed to compare the efficacy and safety of cyclosporine versus placebo, in addition to revascularization by PPCI, in patients presenting with acute anterior myocardial infarction within 12 hours of symptoms onset and initial TIMI flow ≤1 in the culprit left anterior descending coronary artery. Patients are randomized in a 1:1 fashion to 2.5 mg/kg intravenous infusion of cyclosporine or matching placebo performed in the minutes preceding PCI. The primary efficacy end point of CIRCUS is a composite of 1-year all-cause mortality, rehospitalization for heart failure or heart failure worsening during initial hospitalization, and left ventricular adverse remodeling as determined by sequential transthoracic echochardiography. Secondary outcomes will be tested using a hierarchical sequence of left ventricular (LV) ejection fraction and absolute measurements of LV volumes. The composite of death and rehospitalization for heart failure or heart failure worsening during initial hospitalization will be further assessed at three years after the initial infarction.ResultsRecruitment lasted from April 2011 to February 2014. The CIRCUS trial has recruited 975 patients with acute anterior myocardial infarction. The 12-months results are expected to be available in 2015.ConclusionsThe CIRCUS trial is testing the hypothesis that cyclosporine in addition to early revascularization with PPCI compared to placebo in patients with acute anterior myocardial infarction reduces the incidence of death, heart failure and adverse LV remodeling at one-year follow-up.Copyright © 2015 Elsevier Inc. All rights reserved.

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