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A Randomized Controlled Trial

Jean-Claude Tardif, MD; Jean Grégoire, MD; Philippe L. L’Allier, MD; Reda Ibrahim, MD; Jacques Lespérance, MD; Therese M. Heinonen, DVM; Simon Kouz, MD; Colin Berry, MD; Russell Basser, MD; Marc-André Lavoie, MD; Marie-Claude Guertin, PhD; Josep Rodés-Cabau, MD; for the Effect of rHDL on Atherosclerosis-Safety and Efficacy (ERASE) Investigators

JAMA. 2007;297:1675-1682.

Context  High-density lipoprotein (HDL) cholesterol is an inverse predictor of coronary atherosclerotic disease. Preliminary data have suggested that HDL infusions can induce atherosclerosis regression.

Objective  To investigate the effects of reconstituted HDL on plaque burden as assessed by intravascular ultrasound (IVUS).

Design and Setting  A randomized placebo-controlled trial was conducted at 17 centers in Canada. Intravascular ultrasound was performed to assess coronary atheroma at baseline and 2 to 3 weeks after the last study infusion.

Patients  Between July 2005 and October 2006, 183 patients had a baseline IVUS examination and of those, 145 had evaluable serial IVUS examinations after 6 weeks.

Intervention  Sixty patients were randomly assigned to receive 4 weekly infusions of placebo (saline), 111 to receive 40 mg/kg of reconstituted HDL (CSL-111); and 12 to receive 80 mg/kg of CSL-111.

Main Outcome Measures  The primary efficacy parameter was the percentage change in atheroma volume. Nominal changes in plaque volume and plaque characterization index on IVUS and coronary score on quantitative coronary angiography were also prespecified end points.

Results  The higher-dosage CSL-111 treatment group was discontinued early because of liver function test abnormalities. The percentage change in atheroma volume was –3.4% with CSL-111 and –1.6% for placebo (P = .48 between groups, P<.001 vs baseline for CSL-111). The nominal change in plaque volume was –5.3 mm³ with CSL-111 and –2.3 mm³ with placebo (P = .39 between groups, P<.001 vs baseline for CSL-111). The mean changes in plaque characterization index on IVUS (–0.0097 for CSL-111 and 0.0128 with placebo) and mean changes in coronary score (–0.039 mm for CSL-111 and –0.071 mm with placebo) on quantitative coronary angiography were significantly different between groups (P = .01 and P =.03, respectively). Administration of CSL-111 40 mg/kg was associated with mild, self-limiting transaminase elevation but was clinically well tolerated.

Conclusions  Short-term infusions of reconstituted HDL resulted in no significant reductions in percentage change in atheroma volume or nominal change in plaque volume compared with placebo but did result in statistically significant improvement in the plaque characterization index and coronary score on quantitative coronary angiography. Elevation of HDL remains a valid target in vascular disease and further studies of HDL infusions, including trials with clinical end points, appear warranted.

Trial Registration  clinicaltrials.gov Identifier: NCT00225719

Published online: March 26, 2007 (doi:10.1001/jama.297.15.jpc70004).

Author Affiliations: Montreal Heart Institute and the Montreal Heart Institute Coordinating Center (MHICC), Université de Montréal, Montreal, Quebec (Drs Tardif, Grégoire, L’Allier, Ibrahim, Lespérance, Heinonen, Berry, Lavoie, and Guertin); Centre Hospitalier Regional de Lanaudiere, Joliette, Quebec (Dr Kouz); CSL Ltd, Parkville, Australia (Dr Basser); and Quebec Heart Institute–Laval Hospital, Quebec City, Quebec (Dr Rodés-Cabau).

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