Design and rationale of the ARBITER 6 trial (Arterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol)-6-HDL and LDL Treatment Strategies in Atherosclerosis (HALTS)

Abstract

Background: Recent evidence on the use of statin therapy indicates the potential for ultra-low levels of LDL-C to provide greater protection from recurrent coronary heart disease events. Guidelines for the treatment of lipid disorders were revised to indicate that an LDL-C treatment goal of 70 mg/dl was optional (NCEP ATPIII). In these same guidelines, low levels of HDL-C are also suggested but not specifically proscribed as a target of therapy. Recently ARBITER 2 (Arterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol 2) has provided the first evidence of the potential of raising HDL-C with extended release niacin when added to statin monotherapy in secondary prevention. However, whether this approach would be superior to a strategy in which lower concentrations of LDL-C are targeted is unknown.

Materials and methods: ARBITER 6-HALTS ( HDL and LDL Treatment Strategies) will be a randomized, parallel group, open-label study comparing HDL-C and LDL-C focused strategies of lipid treatments for their effects on atherosclerosis. Up to 400 subjects will be assigned to either intensified LDL-C lowering therapy with ezetimibe or HDL-C raising therapy with extended-release niacin. The primary endpoint is the mean change in the intima-media thickness of the common carotid artery after 14 months. Secondary endpoints include the change in lipid values and lipid subfractions, drug discontinuation due to adverse effects, change in quality of life, and a composite endpoint consisting of all major adverse cardiovascular events.

Conclusion: ARBITER 6-HALTS will guide clinicians on whether a lipid treatment strategy of raising HDL-C or further LDL-C reduction is superior in the secondary prevention of coronary heart disease.