TY - JOUR
T1 - Effects of the high-density lipoprotein mimetic agent CER-001 on coronary atherosclerosis in patients with acute coronary syndromes: a randomized trial
AU - Tardif, Jean-Claude
AU - Ballantyne, Christie M.
AU - Barter, Philip
AU - Dasseux, Jean-Louis
AU - Fayad, Zahi A.
AU - Guertin, Marie-Claude
AU - Kastelein, John J. P.
AU - Keyserling, Constance
AU - Klepp, Heather
AU - Koenig, Wolfgang
AU - L'allier, Philippe L.
AU - Lespérance, Jacques
AU - Lüscher, Thomas F.
AU - Paolini, John F.
AU - Tawakol, Ahmed
AU - Waters, David D.
AU - AUTHOR GROUP
AU - Pfeffer, M.
AU - Brown, V.
AU - Rouleau, J.
AU - Watkins, P.
AU - Wei, L. J.
AU - Gosselin, G.
AU - Chayer, C.
AU - Lanthier, S.
AU - Pelletier, G. B.
AU - Racine, N.
AU - Agarwal, H.
AU - Brilakis, E.
AU - Cannon, L.
AU - Carrié, D.
AU - Corbelli, J.
AU - Coste, P.
AU - de Winter, R.
AU - Diaz, A.
AU - Eisenberg, S.
AU - Ennis, B.
AU - Fajadet, J.
AU - Fam, N.
AU - Fortuin, D.
AU - Gessler, C.
AU - Grines, C.
AU - Guerra, D.
AU - Gum, H.
AU - Haldis, T.
AU - Heestermans, T.
AU - Herrman, J. P.
AU - Huynh, T.
AU - Kedhi, E.
AU - Koren, M.
AU - Kouz, S.
PY - 2014
Y1 - 2014
N2 - High-density lipoproteins (HDLs) have several potentially protective vascular effects. Most clinical studies of therapies targeting HDL have failed to show benefits vs. placebo. To investigate the effects of an HDL-mimetic agent on atherosclerosis by intravascular ultrasonography (IVUS) and quantitative coronary angiography (QCA). 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. Five hundred and seven patients were randomized; 417 and 461 had paired IVUS and QCA measurements, respectively. Patients were randomized to receive 6 weekly infusions of placebo, 3 mg/kg, 6 mg/kg, or 12 mg/kg CER-001. 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. 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. 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; NCT01201837
AB - High-density lipoproteins (HDLs) have several potentially protective vascular effects. Most clinical studies of therapies targeting HDL have failed to show benefits vs. placebo. To investigate the effects of an HDL-mimetic agent on atherosclerosis by intravascular ultrasonography (IVUS) and quantitative coronary angiography (QCA). 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. Five hundred and seven patients were randomized; 417 and 461 had paired IVUS and QCA measurements, respectively. Patients were randomized to receive 6 weekly infusions of placebo, 3 mg/kg, 6 mg/kg, or 12 mg/kg CER-001. 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. 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. 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; NCT01201837
U2 - https://doi.org/10.1093/eurheartj/ehu171
DO - https://doi.org/10.1093/eurheartj/ehu171
M3 - Article
C2 - 24780501
SN - 0195-668X
VL - 35
SP - 3277
EP - 3286
JO - European Heart journal
JF - European Heart journal
IS - 46
ER -