Review of study presented at American Heart Association Scientific Sessions

In the study presented today at the American Heart Association Scientific Sessions in Orlando, Florida today, The Effect of Extended-release Niacin or Ezetimibe Added to Chronic Statin Therapy On Carotid Intima Media Thickness (ARBITER 6-HALTS), study found that:

• Adding the cholesterol drug niacin to a statin improved HDL ("good") cholesterol levels and significantly reduced carotid arterial plaque buildup measured with ultrasound within 8 months, with further improvement seen at the end of the study (14 months).
• An alternative approach, adding ezetimibe to a statin, lowered LDL ("bad") cholesterol to a greater extent, but did not raise HDL. With it, there was no overall effect on arterial build up in the neck arteries as observed on carotid ultrasound.
• The incidence of major cardiovascular events such as fatal and non-fatal heart attack was higher in the ezetimibe group as compared to the niacin group (5 percent vs. 1 percent).

ARBITER-HALTS was a relatively small prospective, randomized, parallel group, open- label, blinded endpoint study conducted at Walter Reed Army Medical Center in Washington, D.C., and Washington Adventist Hospital. It only included 363 adults (80 percent male, average age 68 years) with or at high risk for atherosclerotic cardiovascular disease. All participants were on cholesterol-lowering statin drugs, and their LDL cholesterol was at the treatment goal of under 100 milligrams per deciliter (mg/dL) of blood. Their HDL cholesterol was lower than 50 mg/dL for men and 55 mg/dL for women. Patients were randomly assigned to receive either niacin or ezetimibe in addition to their usual statin. The primary endpoint was the change in the wall thickness of the carotid artery in the neck between the two groups of patients.

In the niacin group. HDL cholesterol rose from 42 mg/dL to 50 mg/dL and there was a significant regression in artery wall thickness. In the ezetimibe group, average LDL cholesterol levels dropped from 83 mg/dL to 66 mg/dL; however no overall change was found in average artery wall thickness.

According to Dr. Norman Lepor, Co-director of Imaging at Westside Medical Imaging in Beverly Hills, Clinical Professor of Medicine at the Geffen School of Medicine at UCLA and the Cedars-Sinai Heart Institute, "the results of this small but important clinical trial reinforce the importance of HDL-cholesterol modification to slow the progression of atherosclerosis in patients with or at risk for the development of coronary artery disease with lower HDL-cholesterol levels. He also states that "it will take larger, randomized, national, multi-center trials for us to validate the differences of cardiovascular event rates observed in this trial.' Dr. Gerald Pohost, the director of cardiovascular imaging at Westside Medical Imaging claims "that future trials will have to use more sensitive technologies such as 3T MR to assess for progression/regression of carotid plaques as well as to better characterize any changes in plaque morphology that may prove even more important then the thickness of the carotid plaque.' According to Dr. Hooman Madyoon, Co-director of Imaging at Westside Medical Imaging, Assistant Clinical Professor of Medicine at the Geffen School of Medicine at UCLA and nd the Cedars-Sinai Heart Institute "future studies evaluate the progression of atherosclerosis in additional vascular territories such as the coronary arteries using CT coronary imaging technology that we have pioneered".

According to Dr. Lepor, "this study shows the importance of HDL-cholesterol modification as an adjunct to statin therapy in patients with lower HDL cholesterol levels at risk for coronary artery disease events with niacin being the first choice in these patients. The niacin used should be the branded Niaspan and not the over the counter preparations. Unfortunately the major limitation of niacin therapy is the intense flushing that can be associated with its use." In terms of managing patients who are on add on ezetimibe therapy, we should stay tuned to the larger trials that are now in progress such as AIM-HIGH (Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides and Impact on Global Health Outcomes), HPS2-THRIVE (Heart Protection Study 2: Treatment of HDL to Reduce the Incidence of Vascular Events) and IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial) to define with a higher level of confidence its role in preventing the manifestations of atherosclerosis.