학술논문
Effects of the high-density lipoprotein mimetic agent CER-001 on coronary atherosclerosis in patients with acute coronary syndromes: a randomized trial†
Document Type
Academic Journal
Author
Tardif, Jean-Claude; Ballantyne, Christie M.; Barter, Philip; Dasseux, Jean-Louis; Fayad, Zahi A.; Guertin, Marie-Claude; Kastelein, John J. P.; Keyserling, Constance; Klepp, Heather; Koenig, Wolfgang; LʼAllier, Philippe L.; Lespérance, Jacques; Lüscher, Thomas F.; Paolini, John F.; Tawakol, Ahmed; Waters, David D.; Pfeffer, M.; Brown, V.; Rouleau, J.; Watkins, P.; Wei, L.J.; Gosselin, G.; Chayer, C.; Lanthier, S.; Pelletier, G.B.; Racine, N.; Agarwal, H.; Brilakis, E.; Cannon, L.; Carrié, D.; Corbelli, J.; Coste, P.; de Winter, R.; Diaz, A.; Eisenberg, S.; Ennis, B.; Fajadet, J.; Fam, N.; Fortuin, D.; Gessler, C.; Grines, C.; Guerra, D.; Gum, H.; Haldis, T.; Heestermans, T.; Herrman, J.P.; Huynh, T.; Kedhi, E.; Koren, M.; Kouz, S.; Krolick, M.; Kumkumian, G.; Lavi, S.; Li, R.J.; Masud, ARZ; McAlhany, C.; McGrew, F.A.; OʼShaughnessy, C.; Oude Ophuis, A.J.M.; Parr, K.; Penny, W.; Pesant, Y.; Post, H.; Robinson, S.; Rodes-Cabau, J.; Roy, A.; Schulman, S.; Spence, F.; Stouffer, G.; Stys, T.; Sussex, B.; Tahirkheli, N.; Tardif, J-C.; Grégoire, J.; ten Berg, J.; van Boven, A.J.; von Birgelen, C.; Weinstein, D.
Source
European Heart Journal. Dec 07, 2014 35(46):3277-3286
Subject
Language
English
ISSN
0195-668X
Abstract
AIM: 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). DESIGN AND SETTING: 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. PATIENTS: Five hundred and seven patients were randomized; 417 and 461 had paired IVUS and QCA measurements, respectively. INTERVENTION: Patients were randomized to receive 6 weekly infusions of placebo, 3 mg/kg, 6 mg/kg, or 12 mg/kg CER-001. MAIN OUTCOME MEASURES: 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 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. CONCLUSION: 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; Registryʼs URL: http://clinicaltrials.gov/ct2/show/NCT01201837?term=cer-001&rank=2; Trial registration number: NCT01201837.