Reconstituted HDL may have some benefit in coronary atherosclerosis

Preliminary research suggests that use of reconstituted HDL may have some benefit in coronary atherosclerosis, according to a JAMA study published online March 26.

The study is being released early to coincide with its presentation at the American College of Cardiology's annual conference.

There is a strong inverse association between high-density lipoprotein (HDL) cholesterol (the "good" cholesterol) and risk of coronary atherosclerotic disease, according to background information in the article. Preliminary data have suggested that HDL infusions can reverse atherosclerosis (the progressive thickening and hardening of the arterial walls as a result of fat deposits on their inner lining).

Jean-Claude Tardif, M.D., of the Montreal Heart Institute, University of Montreal, and colleagues with the Effect of rHDL on Atherosclerosis-Safety and Efficacy (ERASE) study assessed the effects of infusion with a reconstituted HDL, CSL-111, on coronary atherosclerosis. CSL-111 consists of apolipoprotein A-I from human plasma combined with soybean phosphatidylcholine (a type of lipid molecule; the combination product) that chemically and biologically resembles HDL. Between July 2005 and October 2006, intravascular ultrasound (IVUS) and quantitative coronary angiography were performed on 183 patients to assess coronary atheroma (plaque deposit) at baseline and 2 to 3 weeks after the last study infusion. Sixty patients were randomly assigned to receive four 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. This highest dosage was discontinued early because of indications it caused a certain elevation in liver function tests, suggesting possible harmful liver effects.

"This study showed differences in coronary atheroma volume after 4 weekly infusions of CSL-111 or placebo (-3.4 percent vs. -1.6 percent, -5.3 mm vs. -2.3 mm, respectively), but the differences between these groups were not statistically significant. However, CSL-111 may nevertheless potentially induce some favorable vascular effects as seen in the significant reductions of atheroma volume of 3.4 percent or 5.3 mm, with active infusions in the analysis comparing follow-up to baseline values. Although the latter finding is not significantly different when compared with placebo and is only suggestive of a possible favorable treatment effect, both the plaque characterization indexes on IVUS and coronary score on quantitative coronary angiography revealed statistically significant differences between CSL-111 and placebo groups that support this analysis," the authors write.

Whether these findings will translate into clinical benefits to patients is not known. "Elevation of HDL remains a valid target in vascular disease and further clinical evaluation of HDL infusions with CSL-111 with longer follow-up appears warranted," the researchers conclude.

JAMA. 2007;297:(doi:10.1001/jama.297.15.jpc70004). Available pre-embargo to the media at www.jamamedia.org .)

Editor's Note: Funding for this study was provided by CSL Ltd, Parkville, Victoria, Australia. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

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