Filippo Ottani1, Roberto Latini2, Lidia Staszewsky3, Luigi La Vecchia4, Nicola Locuratolo5, Marco Sicuro6, Serge Masson3, Simona Barlera3, Valentina Milani3, Mario Lombardi7, Alessandra Costalunga8, Nadia Mollichelli9, Andrea Santarelli10, Nicoletta De Cesare11, Paolo Sganzerla12, Alberto Boi13, Aldo Pietro Maggioni14, Ugo Limbruno15. 1. Unità Operativa di Cardiologia, Ospedale GB Morgagni, Forlì, Italy. 2. Department of Cardiovascular Research, IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy. Electronic address: roberto.latini@marionegri.it. 3. Department of Cardiovascular Research, IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy. 4. Cardiologia, Ospedale San Bortolo, Vicenza, Italy. 5. Cardiologia, Ospedale San Paolo, Bari, Italy. 6. Cardiologia e UTIC, Ospedale Regionale Umberto Parini, Aosta, Italy. 7. Unità Operativa di Cardiologia, Ospedali Riuniti Villa Sofia, Palermo, Italy. 8. Cardiologia Unità Coronarica, Azienda Ospedaliera Bolognini, Seriate, Italy. 9. S.C. Cardiologia, Azienda Ospedaliera, Desio, Italy. 10. Unità Operativa di Cardiologia, Ospedale Infermi, Rimini Italy. 11. Cardiologia, Policlinico San Marco, Zingonia Osio Sotto, Italy. 12. Cardiologia, Ospedale Treviglio-Caravaggio, Treviglio, Italy. 13. Struttura Complessa di Emodinamica, Azienda Ospedaliera Brotzu, Cagliari, Italy. 14. ANMCO Research Center, Heart Care Foundation, Firenze, Italy. 15. Cardiologia, Ospedale delle Misericordie, Grosseto, Italy.
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 primarypercutaneous 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).
RCT Entities:
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 CsApatients 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).
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