Abstract 2219: High Dose Modified-release Nicotinic Acid Reduces Carotid Atherosclerosis: a Randomized, Placebo-controlled Magnetic Resonance Study
Background: Large clinical outcome studies (AIM-HIGH and HPS-2THRIVE) are underway testing the strategy of adding high dose nicotinic acid (NA) to statin treatment. However, the effect of this on atherosclerosis progression is unknown.
Hypothesis: Nicotinic acid 2g daily would reduce change in carotid wall area, assessed by MRI, compared to placebo.
Methods: We performed a double-blind randomized placebo-controlled study of 2g once daily modified release NA added to background statin therapy in 71 patients with low HDL-C <40 mg/dL and either
known coronary heart disease with type 2 diabetes mellitus or
carotid / peripheral atherosclerosis
The pre-specified primary end point was the change in carotid artery wall area, assessed by MRI, after 1 year. We compared the treatment effect using a mixed effect model adjusting for baseline covariates.
Results: 22/35 NA and 29/36 placebo patients completed MRI at all time points. Baseline characteristics were similar. In the NA treated group, HDL-C increased 23% (39±6 to 48±7 mg/dL), and LDL-C decreased 19% (85±23 to 69±21 mg/dL). At 12 months, the NA group had a significantly higher reduction in carotid wall area compared to placebo (adjusted treatment difference [95% CI] = −1.64 mm2 [−3.12, −0.16]; P=0.03). Median (IQR) change in carotid wall area was −1.42 mm2 (−2.65, 0.79) for NA and 0.47 mm2 (−0.97, 2.59) for placebo. At 12 months the change in carotid plaque index (calculated by the recognised method of normalising wall area to total vessel area) was also reduced compared to placebo (treatment difference −0.016 [−0.03, −0.0022]; P = 0.02). Even as early as six months, although there was no treatment difference for change in absolute carotid wall area (−0.98 mm2 [−2.45, 0.49]; P = 0.2), change in carotid plaque index was already significantly lower in the NA treated group (−0.016 [−0.03, 0.0019]; P = 0.03).
Conclusions: This is the first demonstration that addition of high dose modified-release nicotinic acid, to statin-treated patients with low HDL-C, reduces carotid atherosclerosis at 12 months compared to placebo.