Effects of the high-density lipoprotein mimetic agent CER-001 on coronary atherosclerosis in patients with acute coronary syndromes: a randomized trial.
OBJECTIVE
High-density lipoproteins (HDLs) have several potentially protective vascular effects. Most clinical studies of therapies targeting HDL have failed to show benefits vs. placebo.


OBJECTIVE
To investigate the effects of an HDL-mimetic agent on atherosclerosis by intravascular ultrasonography (IVUS) and quantitative coronary angiography (QCA).


METHODS
A prospective, double-blinded, randomized trial was conducted at 51 centres in the USA, the Netherlands, Canada, and France. Intravascular ultrasonography and QCA were performed to assess coronary atherosclerosis at baseline and 3 (2-5) weeks after the last study infusion.


METHODS
Five hundred and seven patients were randomized; 417 and 461 had paired IVUS and QCA measurements, respectively.


METHODS
Patients were randomized to receive 6 weekly infusions of placebo, 3 mg/kg, 6 mg/kg, or 12 mg/kg CER-001.


METHODS
The primary efficacy parameter was the nominal change in the total atheroma volume. Nominal changes in per cent atheroma volume on IVUS and coronary scores on QCA were also pre-specified endpoints.


RESULTS
The nominal change in the total atheroma volume (adjusted means) was -2.71, -3.13, -1.50, and -3.05 mm(3) with placebo, CER-001 3 mg/kg, 6 mg/kg, and 12 mg/kg, respectively (primary analysis of 12 mg/kg vs. placebo: P = 0.81). There was also no difference among groups for the nominal change in per cent atheroma volume (0.02, -0.02, 0.01, and 0.19%; nominal P = 0.53 for 12 mg/kg vs. placebo). Change in the coronary artery score was -0.022, -0.036, -0.022, and -0.015 mm (nominal P = 0.25, 0.99, 0.55), and change in the cumulative coronary stenosis score was -0.51, 2.65, 0.71, and -0.77% (compared with placebo, nominal P = 0.85 for 12 mg/kg and nominal P = 0.01 for 3 mg/kg). The number of patients with major cardiovascular events was 10 (8.3%), 16 (13.3%), 17 (13.7%), and 12 (9.8%) in the four groups.


CONCLUSIONS
CER-001 infusions did not reduce coronary atherosclerosis on IVUS and QCA when compared with placebo. Whether CER-001 administered in other regimens or to other populations could favourably affect atherosclerosis must await further study. Name of the trial registry: Clinicaltrials.gov; Registry's URL: http://clinicaltrials.gov/ct2/show/NCT01201837?term=cer-001&rank=2;


BACKGROUND
NCT01201837.
Jean-Claude
JC
Tardif
Christie M
CM
Ballantyne
Philip
P
Barter
Jean-Louis
JL
Dasseux
Zahi A
ZA
Fayad
Marie-Claude
MC
Guertin
John J P
JJ
Kastelein
Constance
C
Keyserling
Heather
H
Klepp
Wolfgang
W
Koenig
Philippe L
PL
L'Allier
Jacques
J
Lespérance
Thomas F
TF
Lüscher
John F
JF
Paolini
Ahmed
A
Tawakol
David D
DD
Waters
D054058:Acute Coronary Syndrome / Q000000981:diagnostic imaging / Q000188:drug therapy*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016632:Apolipoprotein A-I / Q000008:administration & dosage* / Q000009:adverse effects; D002317:Cardiovascular Agents / Q000008:administration & dosage* / Q000009:adverse effects; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000000981:diagnostic imaging / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D010743:Phospholipids / Q000008:administration & dosage* / Q000009:adverse effects; D011446:Prospective Studies; D011994:Recombinant Proteins / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome; D014463:Ultrasonography
D016632:Apolipoprotein A-I; C000591544:CER-001; D002317:Cardiovascular Agents; D010743:Phospholipids; D011994:Recombinant Proteins
Atherosclerosis; Clinical trial; Coronary disease; High-density lipoproteins