Cyclosporine A in Reperfused Myocardial Infarction: The Multicenter, Controlled, Open-Label CYCLE Trial
Filippo Ottani, Roberto Latini, Lidia Staszewsky, Luigi La Vecchia, Nicola Locuratolo, Marco Sicuro, Serge Masson, Simona Barlera, Valentina Milani, Mario Lombardi, Alessandra Costalunga, Nadia Mollichelli, Andrea Santarelli, Nicoletta De Cesare, Paolo Sganzerla, Alberto Boi, Aldo Pietro Maggioni, Ugo Limbruno, CYCLE Investigators, Filippo Ottani, Roberto Latini, Lidia Staszewsky, Luigi La Vecchia, Nicola Locuratolo, Marco Sicuro, Serge Masson, Simona Barlera, Valentina Milani, Mario Lombardi, Alessandra Costalunga, Nadia Mollichelli, Andrea Santarelli, Nicoletta De Cesare, Paolo Sganzerla, Alberto Boi, Aldo Pietro Maggioni, Ugo Limbruno, CYCLE Investigators
Abstract
Background: Whether cyclosporine A (CsA) has beneficial effects in reperfused myocardial infarction (MI) is debated.
Objectives: 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).
Keywords: acute myocardial infarction; echocardiography; left ventricular function; troponins.
Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
Source: PubMed