Does Cyclosporine Improve Clinical Outcome in ST Elevation Myocardial Infarction Patients - CIRCUS

Aug 30, 2015
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Author/Summarized by Author:
Anthony A. Bavry, MD, MPH, FACC
Summary Reviewer:
Deepak L. Bhatt, MD, MPH, MBA, FACC
Trial Sponsor:
French Ministry of Health, and NeuroVive Pharmaceutical
Date Presented:
08/30/2015
Date Published:
08/30/2015
Original Posted Date:
08/30/2015
References

Description:

The goal of the trial was to evaluate treatment with cyclosporine compared with placebo among subjects undergoing primary percutaneous coronary intervention (PCI) for anterior ST-segment elevation myocardial infarction (STEMI).

Contribution to the Literature: The CIRCUS trial failed to show that cyclosporine improved clinical outcomes or prevented adverse LV remodeling in anterior STEMI.

Study Design

  • Randomized
  • Parallel
  • Blinded
  • Stratified

Subjects with anterior STEMI were randomized to intravenous cyclosporine 2.5 mg/kg (n = 475) versus placebo (n = 495) immediately before coronary reperfusion.

  • Total number of enrollees: 970
  • Duration of follow-up: 1 year
  • Mean patient age: 60 years
  • Percentage female: 16%
  • Percentage diabetics: 14%
  • Thrombus aspiration was performed in 76%

Inclusion criteria:

  • Anterior STEMI within 12 hours of symptom onset
  • Culprit artery was the left anterior descending (LAD) with Thrombolysis in Myocardial Infarction (TIMI) 0 or 1 flow

Exclusion criteria:

  • Cardiogenic shock
  • Coronary collateral circulation

Principal Findings:

The primary outcome of all-cause death, worsening heart failure during the index hospitalization, rehospitalization for heart failure, or adverse left ventricular (LV) remodeling within 1 year occurred in 59.0% of the cyclosporine group versus 58.1% of the placebo group (p = 0.77).

Secondary outcomes:

  • All-cause death: 7.1% vs. 6.6% (p = 0.76), respectively for cyclosporine vs. placebo
  • Rehospitalization for heart failure: 10.6% vs. 10.4% (p = 0.89), respectively for cyclosporine vs. placebo
  • LV remodeling: 42.8% vs. 40.7% (p = 0.53), respectively for cyclosporine vs. placebo

Interpretation:

Among patients with anterior STEMI undergoing primary PCI, intravenous cyclosporine failed to improve clinical outcomes or prevent adverse LV remodeling. Prevention of reperfusion injury has remained an elusive target in the management of acute MI.

References:

Cung TT, Morel O, Cayla G, et al. Cyclosporine Before PCI in Patients With Acute Myocardial Infarction. N Engl J Med 2015;Aug 30:[Epub ahead of print].

Editorial: Hausenloy DJ, Yellon DM. Targeting Myocardial Reperfusion Injury — The Search Continues. N Engl J Med 2015;Aug 30:[Epub ahead of print].

Presented by Dr. Michel Ovize at the European Society of Cardiology Congress, London, August 30, 2015.

Keywords: Acute Coronary Syndrome, Cyclosporine, Heart Failure, Myocardial Infarction, Myocardial Reperfusion Injury, Percutaneous Coronary Intervention, Secondary Prevention, Ventricular Remodeling


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