Plaque Regression and Endothelial Progenitor Cell Mobilization With Intensive Lipid Elimination Regimen (PREMIER)

Background:
Low-density lipoproteins (LDL) are removed by extracorporeal filtration during LDL-apheresis (LDLA-A). It is mainly used in familial hypercholesterolemia (FH). PREMIER is a U.S. Food and Drug Administration Investigational Device Exemption clinical trial to evaluate LDL-A in non-FH acute coronary syndrome (ACS) patients treated with percutaneous coronary intervention (PCI).

Methods:
We randomized 160 ACS patients at 4 VA centers within 72h of an uncomplicated PCI to intensive lipid lowering comprising single LDL-A vs no LDL-A on background statin therapy. Trial objectives constituted primary safety and primary efficacy endpoints and endothelial progenitor cell-colony forming units (EPC-CFU/ml) mobilization in peripheral blood.

Results:
Both treatment groups were comparable at baseline. Mean LDL reduction at discharge was 53% in LDL-A and 17% in no LDL-A groups (p<0.0001). Primary safety endpoints were similar in both groups. The primary efficacy endpoint, percent change in atheroma volume at 90 days by intravascular ultrasound, on average decreased by 5.46% (95% CI, -10.11 to -0.81) in LDL-A group and increased by 2.59% (95% CI, -4.46 to 9.64) in no LDL-A group (p=0.06). EPC-CFU/ml increased from baseline to 90-day follow-up in similar time trends for LDL-A (12.4 to 20.0) and no LDL-A (12.3 to 16.4; p=0.10) groups.

Conclusions:
PREMIER is the first randomized clinical trial to demonstrate safety and a strong trend for early coronary atheroma regression with LDL-apheresis in non-FH ACS patients treated with PCI.