title: Cyclosporine A in Reperfused Myocardial Infarction: The Multicenter, Controlled, Open-Label CYCLE Trial.
abstract: BACKGROUND
  Whether cyclosporine A (CsA) has beneficial effects in reperfused myocardial infarction (MI) is debated.
  
  
  OBJECTIVE
  This study investigated whether CsA improved ST-segment resolution in a randomized, multicenter phase II study.
  
  
  METHODS
  The authors randomly assigned 410 patients from 31 cardiac care units, age 63 ± 12 years, with large ST-segment elevation MI within 6 h of symptom onset, Thrombolysis In Myocardial Infarction (TIMI) flow grade 0 to 1 in the infarct-related artery, and committed to primary percutaneous coronary intervention, to 2.5 mg/kg intravenous CsA (n = 207) or control (n = 203) groups. The primary endpoint was incidence of ≥70% ST-segment resolution 60 min after TIMI flow grade 3. Secondary endpoints included high-sensitivity cardiac troponin T (hs-cTnT) on day 4, left ventricular (LV) remodeling, and clinical events at 6-month follow-up.
  
  
  RESULTS
  Time from symptom onset to first antegrade flow was 180 ± 67 min; a median of 5 electrocardiography leads showed ST-segment deviation (quartile [Q]1 to Q3: 4 to 6); 49.8% of MIs were anterior. ST-segment resolution ≥70% was found in 52.0% of CsA patients and 49.0% of controls (p = 0.55). Median hs-cTnT on day 4 was 2,160 (Q1 to Q3: 1,087 to 3,274) ng/l in CsA and 2,068 (1,117 to 3,690) ng/l in controls (p = 0.85). The 2 groups did not differ in LV ejection fraction on day 4 and at 6 months. Infarct site did not influence CsA efficacy. There were no acute allergic reactions or nonsignificant excesses of 6-month mortality (5.7% CsA vs. 3.2% controls, p = 0.17) or cardiogenic shock (2.4% CsA vs. 1.5% controls, p = 0.33).
  
  
  CONCLUSIONS
  In the CYCLE (CYCLosporinE A in Reperfused Acute Myocardial Infarction) trial, a single intravenous CsA bolus just before primary percutaneous coronary intervention had no effect on ST-segment resolution or hs-cTnT, and did not improve clinical outcomes or LV remodeling up to 6 months. (CYCLosporinE A in Reperfused Acute Myocardial Infarction [CYCLE]; NCT01650662; EudraCT number 2011-002876-18).
authors.affiliation: Unità Operativa di Cardiologia, Ospedale GB Morgagni, Forlì, Italy.
authors.forename: Filippo
authors.initials: F
authors.lastname: Ottani
authors.affiliation: Department of Cardiovascular Research, IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy. Electronic address: roberto.latini@marionegri.it.
authors.forename: Roberto
authors.initials: R
authors.lastname: Latini
authors.affiliation: Department of Cardiovascular Research, IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
authors.forename: Lidia
authors.initials: L
authors.lastname: Staszewsky
authors.affiliation: Cardiologia, Ospedale San Bortolo, Vicenza, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: La Vecchia
authors.affiliation: Cardiologia, Ospedale San Paolo, Bari, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Locuratolo
authors.affiliation: Cardiologia e UTIC, Ospedale Regionale Umberto Parini, Aosta, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Sicuro
authors.affiliation: Department of Cardiovascular Research, IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
authors.forename: Serge
authors.initials: S
authors.lastname: Masson
authors.affiliation: Department of Cardiovascular Research, IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Barlera
authors.affiliation: Department of Cardiovascular Research, IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Milani
authors.affiliation: Unità Operativa di Cardiologia, Ospedali Riuniti Villa Sofia, Palermo, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Lombardi
authors.affiliation: Cardiologia Unità Coronarica, Azienda Ospedaliera Bolognini, Seriate, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Costalunga
authors.affiliation: S.C. Cardiologia, Azienda Ospedaliera, Desio, Italy.
authors.forename: Nadia
authors.initials: N
authors.lastname: Mollichelli
authors.affiliation: Unità Operativa di Cardiologia, Ospedale Infermi, Rimini Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Santarelli
authors.affiliation: Cardiologia, Policlinico San Marco, Zingonia Osio Sotto, Italy.
authors.forename: Nicoletta
authors.initials: N
authors.lastname: De Cesare
authors.affiliation: Cardiologia, Ospedale Treviglio-Caravaggio, Treviglio, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Sganzerla
authors.affiliation: Struttura Complessa di Emodinamica, Azienda Ospedaliera Brotzu, Cagliari, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Boi
authors.affiliation: ANMCO Research Center, Heart Care Foundation, Firenze, Italy.
authors.forename: Aldo Pietro
authors.initials: AP
authors.lastname: Maggioni
authors.affiliation: Cardiologia, Ospedale delle Misericordie, Grosseto, Italy.
authors.forename: Ugo
authors.initials: U
authors.lastname: Limbruno
mesh_terms: D017023:Coronary Angiography; D016572:Cyclosporine / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004452:Echocardiography; D004562:Electrocardiography; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000175:diagnosis / Q000503:physiopathology / Q000628:therapy*; D015425:Myocardial Reperfusion / Q000379:methods*; D011446:Prospective Studies; D016896:Treatment Outcome; D016277:Ventricular Function, Left / Q000502:physiology*; D020257:Ventricular Remodeling / Q000187:drug effects*
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine
keywords: acute myocardial infarction; echocardiography; left ventricular function; troponins