Arterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol 2 ARBITER-2 Trial Presented at The American Heart Association Scientific Sessions 2004 Presented by Dr. A. Taylor

www. Clinical trial results.org Primary Endpoint:  Change in mean common carotid intimal medial thickness (IMT) at 1 year within each study group Primary Endpoint:  Change in mean common carotid intimal medial thickness (IMT) at 1 year within each study group ARBITER-2 Trial Presented at AHA 2004 Placebo Concomitant statin therapy Placebo Concomitant statin therapy 167 Coronary heart disease patients with low HDL cholesterol levels (<45 mg/dl) pre-treated with statin therapy Mainly simvostatin, average 35 mg for 4.5 years Average baseline lipids: 89 mg/dL LDL, 40 mg/dL HDL, 157 mg/dL total cholesterol Mean age 67, 89% male 167 Coronary heart disease patients with low HDL cholesterol levels (<45 mg/dl) pre-treated with statin therapy Mainly simvostatin, average 35 mg for 4.5 years Average baseline lipids: 89 mg/dL LDL, 40 mg/dL HDL, 157 mg/dL total cholesterol Mean age 67, 89% male Extended Release Niacin 500 mg/day - first month 1000mg/ day - remaining 11 months Concomitant statin therapy Extended Release Niacin 500 mg/day - first month 1000mg/ day - remaining 11 months Concomitant statin therapy

www. Clinical trial results.org ARBITER-2 Trial: Primary endpoint The change in carotid IMT at 1 year shows a trend toward slowed atherosclerotic progression in the niacin group, but the result is not statistically significant The primary endpoint of increase in carotid IMT from baseline to 12 months is statistically significant in the placebo arm (p=<0.001), but not in the Niacin arm (p=0.23) Increase in carotid IMT at 12 months p = 0.08 Presented at AHA 2004

www. Clinical trial results.org ARBITER-2: HDL Mean HDL increased significantly from baseline to 12 months in the Niacin treatment group (p=<0.001), but did not change in the placebo group, resulting in significantly higher 12-month HDL levels in the niacin group compared to the placebo group (p=0.003). Presented at AHA 2004 Mean HDL levels at baseline and 12 months p=0.003

www. Clinical trial results.org ARBITER-2: Triglyceride Triglyceride levels decreased from baseline to 12 months in both the niacin and placebo groups, but the decrease was only statistically significant in the niacin group (p=0.009). This combined with the initially lower levels in the niacin group resulted in significantly lower 12-month triglyceride levels in the niacin group compared to placebo (p=0.03) Presented at AHA 2004 p=0.03 Triglyceride levels at baseline and 12 months

www. Clinical trial results.org ARBITER-2 Trial: Safety Cardiovascular events occurred in 3 patients in the niacin arm and 7 patients in the placebo arm, not enough to show a statistical difference between the two treatments The two groups also experienced similar rates of study drug discontinuation Skin Flushing, however, was significantly higher in the niacin group p<0.001 Cardiovascular Events p=0.2 Presented at AHA 2004

www. Clinical trial results.org ARBITER - 2: Summary Among coronary heart disease patients on statin therapy with controlled LDL cholesterol levels and low HDL cholesterol levels, treatment with placebo was associated with a significant increase in mean carotid IMT from baseline to 1 year, while no significant increase in IMT occurred in the niacin group. The total increase bordered on being significantly lower in the niacin group than in the placebo group The lipid profile of the niacin group significantly improved from baseline to 12 months with both increased mean HDL and decreased triglyceride levels. There was no significant change in the lipid profile of the placebo group from baseline to 12 months. The net result was significantly higher one-year HDL levels and significantly lower one-year triglyceride levels in the niacin group compared to the placebo group There was no significant difference between the two treatments in incidence of adverse events or side effects, except for skin flushing, which was higher in the niacin group This was the first study to show an additional benefit of niacin therapy in patients with low, statin-controlled LDL levels (mean baseline of study = 89 mg/dL) Mean carotid IMT was used as a marker of progression of atherosclerosis. Further study of the effect of niacin on clinical outcomes is warranted. Among coronary heart disease patients on statin therapy with controlled LDL cholesterol levels and low HDL cholesterol levels, treatment with placebo was associated with a significant increase in mean carotid IMT from baseline to 1 year, while no significant increase in IMT occurred in the niacin group. The total increase bordered on being significantly lower in the niacin group than in the placebo group The lipid profile of the niacin group significantly improved from baseline to 12 months with both increased mean HDL and decreased triglyceride levels. There was no significant change in the lipid profile of the placebo group from baseline to 12 months. The net result was significantly higher one-year HDL levels and significantly lower one-year triglyceride levels in the niacin group compared to the placebo group There was no significant difference between the two treatments in incidence of adverse events or side effects, except for skin flushing, which was higher in the niacin group This was the first study to show an additional benefit of niacin therapy in patients with low, statin-controlled LDL levels (mean baseline of study = 89 mg/dL) Mean carotid IMT was used as a marker of progression of atherosclerosis. Further study of the effect of niacin on clinical outcomes is warranted.