Can Hdl Infusions Significantly QUicken Atherosclerosis REgression - CHI-SQUARE

Aug 04, 2014
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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:
Cerenis
Date Published:
01/01/2014
Date Updated:
08/04/2014
Original Posted Date:
08/04/2014
References

Description:

The goal of the trial was to evaluate treatment with CER-001, an engineered lipoprotein particle that resembles high-density lipoprotein (HDL) cholesterol, compared with placebo among patients with recent acute coronary syndrome (ACS).

Hypothesis:

CER-001 will reduce coronary total atheroma volume.

Study Design

  • Randomized
  • Blinded
  • Parallel

Patient Populations:

  • Patients who underwent coronary angiography for ACS and had a baseline IVUS performed

    Number of screened applicants: 1,077 patients
    Number of enrollees: 470 patients
    Duration of follow-up: 6 weeks
    Mean patient age: 59 years
    Percentage female: 27%

Exclusions:

  • Left main stenosis
  • Poor-quality baseline IVUS
  • Liver disease
  • Uncontrolled diabetes or hypertension
  • Hemodynamic instability
  • Class III or IV heart failure
  • Ejection fraction <35%
  • Previous or planned coronary bypass surgery
  • Planned valve surgery
  • Drug or alcohol abuse

Primary Endpoints:

  • Change in coronary total atheroma volume

Secondary Endpoints:

  • Change in coronary percent atheroma volume

Drug/Procedures Used:

Within 14 days of an ACS and baseline intravascular ultrasound (IVUS), patients were randomized to 6 weekly intravenous infusions of CER-001 (3 mg/kg, n = 116), CER-001 (6 mg/kg, n = 120), CER-001 (12 mg/kg, n = 116) versus placebo (n = 118).

Principal Findings:

Overall, 470 patients were randomized. The mean age was 59 years, 73% were men, 31% had diabetes, and 97% were on a lipid-lowering agent. Patient presentation was unstable angina in 55%, non–ST-segment myocardial infarction (NSTEMI) in 35%, and STEMI in 10%.

The nominal change in coronary total atheroma volume was -3.13 for CER-001 (3 mg/kg), -1.50 for CER-001 (6 mg/kg), and -3.05 for CER-001 (12 mg/kg); CER-001 (12 mg/kg) versus placebo (p = 0.81).

The nominal change in coronary percent atheroma volume was -0.02 for CER-001 (3 mg/kg), 0.01 for CER-001 (6 mg/kg), and 0.19 for CER-001 (12 mg/kg); CER-001 (12 mg/kg) versus placebo (p = 0.53).

Any major adverse cardiac events (MACE): 13.3% for CER-001 (3 mg/kg), 13.7% for CER-001 (6 mg/kg), 9.8% for CER-001 (12 mg/kg), and 8.3% for placebo.

IVUS images were re-analyzed at the request of the sponsor, which yielded similar results.

Interpretation:

Among patients with recent ACS, 6 weeks of HDL infusion in addition to standard lipid-lowering therapy was not able to significantly regress coronary atherosclerosis. An inverse relationship exists between HDL cholesterol levels and risk of cardiovascular events; however, this relationship appears to be weakened in patients with established coronary disease. To date, attempts to raise HDL cholesterol levels have not improved clinical outcomes (for example, AIM-HIGH, HPS2-THRIVE, dal-OUTCOMES, ERASE).

References:

Tardif JC, Ballantyne CM, Barter P, et al., on behalf of the Can Hdl Infusions Significantly QUicken Atherosclerosis REgression (CHI-SQUARE) Investigators. Effects of the high-density lipoprotein mimetic agent CER-001 on coronary atherosclerosis in patients with acute coronary syndromes: a randomized trial. Eur Heart J 2014;Apr 29:[Epub ahead of print].

Keywords: Coronary Artery Disease, Myocardial Infarction, Acute Coronary Syndrome, Cardiovascular Agents, Plaque, Atherosclerotic, Cholesterol, HDL, Lipoproteins, HDL, Infusions, Intravenous, Diabetes Mellitus


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