In patients with anterior STEMI, the immunosuppressant drug cyclosporine does not appear to improve clinical outcomes, according to results from the CIRCUS trial.
The drug, administered prior to receiving percutaneous coronary intervention (PCI) for the more severe form of heart attack known as ST-segment elevation myocardial infarction (STEMI), had no impact on a composite of all-cause death, hospitalisation for, or worsening of, heart failure, or adverse left ventricular remodelling after one year.
Lead investigator Michel Ovize, MD, PhD, from Claude Bernard University, in Lyon, France, said:
“We were very surprised and disappointed. There is substantial experimental evidence that cyclosporine can reduce infarct size and improve cardiac function, and we previously published a small-size phase II trial suggesting that cyclosporine may reduce infarct size in STEMI patients (N Engl J Med. 2008 Jul 31;359(5):473-81). Obviously, the larger phase III CIRCUS study did not confirm this, and the reason for this discrepancy in unclear.”
The study involved patients with anterior STEMI undergoing PCI within 12 hours of symptom onset and with complete occlusion of the culprit coronary artery.
Patients were randomly assigned to receive a 2.5 mg/kg intravenous bolus injection of cyclosporine (n=395) or matching placebo (n=396) before coronary recanalization.
“The real-life setting of anterior STEMI is quite different from animal models and, in addition, treatment of patients has changed in several ways since our previous study,” said Professor Ovize. “Targeting reperfusion injury to reduce infarct size remains a major challenge for PCI cardiologists in charge of STEMI patients whose cardiovascular risk remains much too high.”
Christophe Piot, M.D., Ph.D., et al.
Effect of Cyclosporine on Reperfusion Injury in Acute Myocardial Infarction
N Engl J Med 2008; 359:473-481July 31, 2008DOI: 10.1056/NEJMoa071142
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