Comparative Study of the Effect of Ezetimibe Versus Extended-Release Niacin on Atherosclerosis
Comparative Study of the Effect of Ezetimibe Versus Extended-Release Niacin on Atherosclerosis
Recent evidence on the use of statin therapy indicates the potential for ultra-low levels of
 low-density lipoprotein (LDL-C) to provide greater protection from recurrent coronary heart
 disease (CHD) events. Thus, in August 2005, the guidelines for the treatment of lipid
 disorders (NCEP ATPIII) were revised to indicate that an LDL-C treatment goal of 70 mg/dL
 (revised from 100 mg/dL) was optional for patients with known CHD. In these same guidelines,
 low levels of high-density lipoprotein (HDL-C) are also suggested but not specifically
 proscribed as a target of therapy. Recently the ARBITER 2 trial has provided the first
 evidence of the potential of raising HDL-C with extended release niacin when added to statin
 monotherapy. However, whether this approach would be superior to a strategy in which lower
 concentrations of LDL-C are targeted is unknown.

 The purpose of ARBITER 6 - HALTS is to compare HDL and LDL-focused strategies of lipid
 treatments for their effects of atherosclerosis. This study is a prospective, randomized,
 open-label, blinded endpoint trial comparing treatment strategies of either HDL-raising
 therapies or LDL reduction for dyslipidemia on carotid atherosclerosis. Subjects with known
 atherosclerotic coronary or vascular disease or otherwise at high cardiovascular risk through
 the presence of a coronary risk equivalent who are currently being treated with a statin will
 be eligible. Subjects will be randomly assigned in an allocation-concealed fashion to open
 label treatment with either Ezetimibe 10 mg/d for additional LDL-lowering OR Extended-release
 niacin (1 gm/d, titrated to max tolerable dose up to 2 gm/d) for HDL improvement.

 The effects of these 2 different strategies of intensified lipid management on
 atherosclerosis will be assessed by the change in the carotid intima-media thickness, a
 validated surrogate endpoint. The data will help guide clinicians on the potential benefits
 of these lipid treatment strategies.
Inclusion Criteria:

 -  Male and female subjects, ≥ 30 years old with either known atherosclerotic coronary or
 vascular disease OR coronary risk equivalents defined as either:

 -  diabetes mellitus,

 -  multiple coronary risk factors with a Framingham Risk Score > 2% per year, or

 -  an elevated coronary calcium score (> 400 for men, > 200 for women)

 -  Currently being treated with a statin (Simvastatin 20 mg/d or its equivalent) as
 monotherapy for treatment of hyperlipidemia

 -  Recent lipids (within the past 3 months without interval change in the statin regimen)
 showing both: LDL-C < 100 mg/dL and HDL-C < 50 mg/dL (men) or < 55 mg/dL (women)

 Exclusion Criteria:

 -  Current use of or known intolerance to niacin or ezetimibe

 -  Known history of liver disease (cirrhosis, chronic hepatitis) or abnormal liver
 associated enzymes, > 3x the upper laboratory reference value

 -  Enrollment in another drug or device research protocol

 -  Females who are pregnant, expect to get pregnant during the course of the study, or
 are breastfeeding