1. Oxford Niacin Trial

2. Trial rationale
This trial tested the hypothesis that raising HDL-C in statin-treated patients with CHD or CHD risk equivalents and low HDL-C would reduce atherosclerosis progression.
This rationale is supported by findings from the ARBITER-2 and ARBITER-3 studies.
Previous studies such as HATS (HDL-Atherosclerosis Treatment Study) (1) and ARBITER 2 and 3 (ARterial Biology for the Investigation of the Treatment Effects of Reducing cholesterol study) (2,3) have suggested that adding niacin (nicotinic acid) to statin therapy reduces coronary atheroma. These studies supported the rationale for this trial.
References
1. Brown BG, Zhao XQ, Chait A et al. N Engl J Med 2001;345:
2. Taylor AJ, Sullenberger LE, Lee HJ et al. Circulation 2004;110:
3. Taylor AJ, Lee HJ, Sullenberger LE. Curr Med Res Opin 2006;22:
Lee et al. JACC 2009; 54:

3. End points
Primary
Absolute change in carotid artery wall area at 12 months, assessed by MRI.
Secondary
Blood lipids, CRP and adiponectin.
This double-blind study included 71 statin-treated patients with low HDL cholesterol (<40 mg/dL) and either type 2 diabetes with CHD or clinical evidence of carotid or peripheral atherosclerosis. Patients were randomized to treatment with modified-release nicotinic acid (niacin) (target dose 2 g daily) or placebo for 12 months.
Magnetic resonance imaging was performed at baseline and 6 and 12 months. Fasting blood samples were also taken at these visits for measurement of blood lipids, lipoproteins, CRP, adiponectin and laboratory safety tests. The primary endpoint was the absolute change in carotid artery wall area at 12 months.
Reference
1. Lee JMS, Robson MD, Yu L-M et al. J Am Coll Cardiol 2009;54:
Lee et al. JACC 2009; 54:

4. Lipids at baseline and % change at 12 months
Nicotinic acid
Placebo
HDL-C (mg/dL)
39; +23%*
37; +3%
LDL-C (mg/dL)
85; -19%*
84; -5%
TG (mg/dL)
168; -11%*
192; -6%
Lp(a) (mg/dL)
14; -36%*
14; +29%
apoB (g/L)
0.82; -11%*
0.84; -2%
apoA-I (g/L)
1.27; +4%*
1.20; -2%
Treatment with nicotinic acid for 12 months led to a 23% increase in HDL cholesterol (from 39 mg/dL to 48 mg/dL, p<0.001), 19% decrease in low-density lipoprotein (LDL) cholesterol, as well as significant decreases in triglycerides and Lp(a).
Reference
1. Lee JMS, Robson MD, Yu L-M et al. J Am Coll Cardiol 2009;54:
Mean data except for TG and Lp(a), which are given as median
*Statistically significant vs. placebo
Lee et al. JACC 2009; 54:

5. Change in primary endpoint (mm2) at 12 months
Treatment difference (95% CI)
P-value
Nicotinic acid
-1.1 (2.6)
-1.64 (3.12, -0.16)
0.03
Placebo
+1.2 (3.0)
In the nicotinic acid treatment group there was significant regression of the carotid artery wall area compared with progression in the group receiving statin monotherapy (-1.1  2.6 mm2 vs  3.0 mm2, adjusted treatment difference mm2, 95% CI to ‑0.16, p=0.03). There was also significant reduction in the aortic wall area at 6 months associated with nicotinic acid vs. placebo (estimated treatment difference ‑6.40 mm2, 95% CI to -0.54, p=0.03), although this was not significant at 12 months, possibly due to the small patient numbers in the study.
Reference
1. Lee JMS, Robson MD, Yu L-M et al. J Am Coll Cardiol 2009;54:
Change in carotid artery wall area
Lee et al. JACC 2009; 54:

6. Conclusions
This trial provides the first direct evidence that nicotinic acid (niacin) reduced carotid atherosclerosis within 12 months vs. Placebo in statin-treated patients with low HDL-C and clinical evidence of atherosclerotic disease.
These findings underpin the rationale for AIM-HIGH and HPS2-THRIVE.