Raising high-density lipoprotein (HDL) cholesterol in patients at LDL goal: new study

HDL Forum Editor Professor Philip Barter comments on an interesting and important new lipid trial in patients with persistently low levels of high-density lipoprotein (HDL) cholesterol: Arterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol-6-HDL and LDL Treatment Strategies in Atherosclerosis (ARBITER 6-HALTS).

Devine PJ, Turco MA, Taylor AJ. 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). Cardiovasc Drugs Ther 2007;21:221-5.

A low level of high-density lipoprotein (HDL) cholesterol is as powerful a predictor of cardiovascular disease as is a high level of low-density lipoprotein (LDL) cholesterol. While there is overwhelming evidence that lowering the level of LDL cholesterol reduces cardiovascular risk, there is currently less evidence that raising HDL cholesterol levels has comparable benefit. Moreover some researchers have argued that if LDL cholesterol is reduced to sufficiently low levels, a low HDL cholesterol concentration no longer matters.

ARBITER 6-HALTS plans to study 400 people at high risk of heart disease who have already had their LDL cholesterol reduced to recommended goals by statin monotherapy but who still have a low level of HDL cholesterol. Patients will be randomized to one of two treatment groups. One group will have additional LDL-C lowering by supplementing statin therapy with 10 mg ezetimibe daily and the other group will have their HDL cholesterol raised by the addition of extended-release nicotinic acid (niacin), titrated from an initial dose of 500 mg daily in 2-weekly intervals to the maximum tolerated dose (at least 1 g/day, maximum dose of 2 g/day). The duration of treatment will be 14 months.

The primary endpoint of the trial is the mean change in the intima-media thickness of the common carotid artery at 14 months, which is a validated surrogate for cardiovascular clinical outcome. Secondary endpoints include changes in lipids and lipid subfractions; a composite endpoint of all major adverse cardiovascular events; drug discontinuation due to adverse effects; and quality of life, assessed using the EQ-5D questionnaire.

ARBITER 6-HALTS will provide the first evidence of which strategy is better in people with low HDL cholesterol: reducing LDL cholesterol levels beyond currently recommended targets or increasing HDL cholesterol levels by treatment with nicotinic acid. The results of this trial are awaited with great interest.