In patients with acute anterior ST-segment elevation myocardial infarction (STEMI) referred for primary percutaneous coronary intervention (PCI), intravenous cyclosporine did not result in better clinical outcomes than those with placebo and did not prevent adverse left ventricular remodeling at one year, according to results from the CIRCUS Trial presented Aug. 30 at ESC Congress 2015 in London and simultaneously published in the New England Journal of Medicine (NEJM).

The study enrolled 970 patients with acute anterior STEMI who were undergoing PCI within 12 hours after symptom onset and who had complete occlusion of the culprit coronary artery to receive a bolus injection of cyclosporine or matching placebo before coronary recanalization. According to the study investigators, cyclosporine compared to placebo did not reduce any of the primary outcomes of death from any cause, worsening of heart failure during initial hospitalization, re-hospitalization for heart failure, or adverse left ventricular remodeling at one year. At one year, the rate of the primary outcome was 59 percent in the cyclosporine group and 58.1 percent in the control group.

Other results showed that cyclosporine did not reduce other events like recurrent infarction, unstable angina and stroke. No significant safety differences were observed between the two groups as well. The investigators also pointed out that almost 25 percent of patients in the current trial died or were hospitalized for heart failure despite receiving state-of-the-art medical care. "This finding is a reminder of the substantial residual risk in this population and the persistent room for improvement in the medical treatment of high-risk patients with STEMI," they said. "The results of this trial do not challenge the concept that reperfusion injury is clinically important."

In a corresponding NEJM editorial, Derek J. Hausenloy, MB, ChB, PhD, FACC, and Derek M. Yellon, DSc, PhD, FACC, said the results of the CIRCUS study are disappointing. However, they write that the findings "do not disprove the existence or clinical significance of myocardial reperfusion injury, because it appears that the formulation of cyclosporine used in the study might not have been effective at preventing myocardial reperfusion injury." They suggest that moving forward, "the search to find an effective therapy for preventing myocardial reperfusion injury and improving clinical outcomes in patients with reperfused STEMI should continue."

Keywords: Cyclosporins, ESC Congress, Angina, Unstable, Coronary Vessels, Heart Failure, Hospitalization, Infarction, Myocardial Infarction, Myocardial Reperfusion, Percutaneous Coronary Intervention, Stroke, Ventricular Remodeling

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