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Updated: Mar 26, 2026
A Murine Closed-chest Model of Myocardial Ischemia and Reperfusion
Published on: July 17, 2012
Cyclosporine A in Reperfused Myocardial Infarction: The Multicenter, Controlled, Open-Label CYCLE Trial
Filippo Ottani1, Roberto Latini2, Lidia Staszewsky2
1Unità Operativa di Cardiologia, Ospedale GB Morgagni, Forlì, Italy.
Insights
Cyclosporine A (CsA) did not improve ST-segment resolution or cardiac biomarkers in patients with reperfused myocardial infarction (MI). This randomized trial found no significant benefit in clinical outcomes or left ventricular remodeling up to six months.
Area of Science:
- Cardiology
- Immunology
- Pharmacology
Background:
- The efficacy of Cyclosporine A (CsA) in treating reperfused myocardial infarction (MI) remains a subject of debate.
- Investigating CsA's potential benefits in improving myocardial reperfusion injury is crucial for patient outcomes.
Purpose of the Study:
- To evaluate the effect of intravenous CsA on ST-segment resolution in patients with ST-segment elevation MI undergoing primary percutaneous coronary intervention.
- To assess secondary endpoints including cardiac biomarkers, left ventricular remodeling, and clinical events at six-month follow-up.
Main Methods:
- A randomized, multicenter phase II study involving 410 patients with acute ST-segment elevation MI.
- Patients received either intravenous CsA (2.5 mg/kg) or a control infusion before primary percutaneous coronary intervention.
- Primary endpoint: ST-segment resolution ≥70% at 60 minutes post-reperfusion; secondary endpoints: hs-cTnT, LV remodeling, and clinical events.
Main Results:
- No significant difference in ST-segment resolution (52.0% CsA vs. 49.0% controls, p=0.55) was observed between the groups.
- Median high-sensitivity cardiac troponin T (hs-cTnT) levels on day 4 and left ventricular ejection fraction at 4 days and 6 months were similar.
- No significant differences in 6-month mortality or cardiogenic shock rates were found between CsA and control groups.
Conclusions:
- A single intravenous CsA bolus before primary percutaneous coronary intervention did not improve ST-segment resolution or cardiac biomarkers in reperfused MI.
- CsA treatment did not demonstrate significant benefits in clinical outcomes or left ventricular remodeling up to six months post-MI.
- The CYCLE trial suggests that CsA is not effective for improving outcomes in patients with acute myocardial infarction undergoing reperfusion therapy.
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).
