Can Hdl Infusions Significantly QUicken Atherosclerosis REgression - CHI-SQUARE
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).
CER-001 will reduce coronary total atheroma volume.
- 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%
- 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
- Change in coronary total atheroma volume
- Change in coronary percent atheroma volume
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).
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.
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).
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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