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

Research output: Contribution to journalArticle

63 Citations (Scopus)

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)

Original languageEnglish
Pages (from-to)365-374
Number of pages10
JournalJournal of the American College of Cardiology
Volume67
Issue number4
DOIs
Publication statusPublished - Feb 2 2016

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Cyclosporine
Myocardial Infarction
Troponin T
Ventricular Remodeling
Percutaneous Coronary Intervention
Cardiogenic Shock
Stroke Volume
Hypersensitivity
Electrocardiography
Arteries
Mortality
Incidence

Keywords

  • acute myocardial infarction
  • echocardiography
  • left ventricular function
  • troponins

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Cyclosporine A in Reperfused Myocardial Infarction the Multicenter, Controlled, Open-Label CYCLE Trial. / Ottani, Filippo; Latini, Roberto; Staszewsky, Lidia; La Vecchia, Luigi; Locuratolo, Nicola; Sicuro, Marco; Masson, Serge; Barlera, Simona; Milani, Valentina; Lombardi, Mario; Costalunga, Alessandra; Mollichelli, Nadia; Santarelli, Andrea; De Cesare, Nicoletta; Sganzerla, Paolo; Boi, Alberto; Maggioni, Aldo Pietro; Limbruno, Ugo.

In: Journal of the American College of Cardiology, Vol. 67, No. 4, 02.02.2016, p. 365-374.

Research output: Contribution to journalArticle

Ottani, F, Latini, R, Staszewsky, L, La Vecchia, L, Locuratolo, N, Sicuro, M, Masson, S, Barlera, S, Milani, V, Lombardi, M, Costalunga, A, Mollichelli, N, Santarelli, A, De Cesare, N, Sganzerla, P, Boi, A, Maggioni, AP & Limbruno, U 2016, 'Cyclosporine A in Reperfused Myocardial Infarction the Multicenter, Controlled, Open-Label CYCLE Trial', Journal of the American College of Cardiology, vol. 67, no. 4, pp. 365-374. https://doi.org/10.1016/j.jacc.2015.10.081
Ottani, Filippo ; Latini, Roberto ; Staszewsky, Lidia ; La Vecchia, Luigi ; Locuratolo, Nicola ; Sicuro, Marco ; Masson, Serge ; Barlera, Simona ; Milani, Valentina ; Lombardi, Mario ; Costalunga, Alessandra ; Mollichelli, Nadia ; Santarelli, Andrea ; De Cesare, Nicoletta ; Sganzerla, Paolo ; Boi, Alberto ; Maggioni, Aldo Pietro ; Limbruno, Ugo. / Cyclosporine A in Reperfused Myocardial Infarction the Multicenter, Controlled, Open-Label CYCLE Trial. In: Journal of the American College of Cardiology. 2016 ; Vol. 67, No. 4. pp. 365-374.
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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. 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)",
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author = "Filippo Ottani and Roberto Latini and Lidia Staszewsky and {La Vecchia}, Luigi and Nicola Locuratolo and Marco Sicuro and Serge Masson and Simona Barlera and Valentina Milani and Mario Lombardi and Alessandra Costalunga and Nadia Mollichelli and Andrea Santarelli and {De Cesare}, Nicoletta and Paolo Sganzerla and Alberto Boi and Maggioni, {Aldo Pietro} and Ugo Limbruno",
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TY - JOUR

T1 - Cyclosporine A in Reperfused Myocardial Infarction the Multicenter, Controlled, Open-Label CYCLE Trial

AU - Ottani, Filippo

AU - Latini, Roberto

AU - Staszewsky, Lidia

AU - La Vecchia, Luigi

AU - Locuratolo, Nicola

AU - Sicuro, Marco

AU - Masson, Serge

AU - Barlera, Simona

AU - Milani, Valentina

AU - Lombardi, Mario

AU - Costalunga, Alessandra

AU - Mollichelli, Nadia

AU - Santarelli, Andrea

AU - De Cesare, Nicoletta

AU - Sganzerla, Paolo

AU - Boi, Alberto

AU - Maggioni, Aldo Pietro

AU - Limbruno, Ugo

PY - 2016/2/2

Y1 - 2016/2/2

N2 - 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)

AB - 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)

KW - acute myocardial infarction

KW - echocardiography

KW - left ventricular function

KW - troponins

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JO - Journal of the American College of Cardiology

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