Cyclosporine Before PCI in Patients With Acute Myocardial Infarction

N Engl J Med. 2015 Sep 10;373(11):1021-31. doi: 10.1056/NEJMoa1505489. Epub 2015 Aug 30.

Abstract

Background: Experimental and clinical evidence suggests that cyclosporine may attenuate reperfusion injury and reduce myocardial infarct size. We aimed to test whether cyclosporine would improve clinical outcomes and prevent adverse left ventricular remodeling.

Methods: In a multicenter, double-blind, randomized trial, we assigned 970 patients with an acute anterior ST-segment elevation myocardial infarction (STEMI) who were undergoing percutaneous coronary intervention (PCI) within 12 hours after symptom onset and who had complete occlusion of the culprit coronary artery to receive a bolus injection of cyclosporine (administered intravenously at a dose of 2.5 mg per kilogram of body weight) or matching placebo before coronary recanalization. The primary outcome was a composite of death from any cause, worsening of heart failure during the initial hospitalization, rehospitalization for heart failure, or adverse left ventricular remodeling at 1 year. Adverse left ventricular remodeling was defined as an increase of 15% or more in the left ventricular end-diastolic volume.

Results: A total of 395 patients in the cyclosporine group and 396 in the placebo group received the assigned study drug and had data that could be evaluated for the primary outcome at 1 year. The rate of the primary outcome was 59.0% in the cyclosporine group and 58.1% in the control group (odds ratio, 1.04; 95% confidence interval [CI], 0.78 to 1.39; P=0.77). Cyclosporine did not reduce the incidence of the separate clinical components of the primary outcome or other events, including recurrent infarction, unstable angina, and stroke. No significant difference in the safety profile was observed between the two treatment groups.

Conclusions: In patients with anterior STEMI who had been referred for primary PCI, intravenous cyclosporine did not result in better clinical outcomes than those with placebo and did not prevent adverse left ventricular remodeling at 1 year. (Funded by the French Ministry of Health and NeuroVive Pharmaceutical; CIRCUS ClinicalTrials.gov number, NCT01502774; EudraCT number, 2009-013713-99.).

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Combined Modality Therapy
  • Cyclophilins / antagonists & inhibitors*
  • Cyclosporine / administration & dosage*
  • Cyclosporine / adverse effects
  • Double-Blind Method
  • Electrocardiography
  • Enzyme Inhibitors / administration & dosage*
  • Enzyme Inhibitors / adverse effects
  • Female
  • Heart Failure / epidemiology
  • Humans
  • Injections, Intravenous
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Mortality
  • Myocardial Infarction / drug therapy*
  • Myocardial Infarction / therapy
  • Percutaneous Coronary Intervention*
  • Ventricular Remodeling / drug effects*

Substances

  • Enzyme Inhibitors
  • Cyclosporine
  • Cyclophilins
  • PPID protein, human

Associated data

  • ClinicalTrials.gov/NCT01502774
  • EudraCT/2009-013713-99