Flushing and the HDL-C response to extended-release niacin

Several lines of evidence suggest that a linkage between niacin efficacy and flushing is plausible.

To examine the relationship between niacin-induced flushing and clinical endpoints among participants of the Arterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol (ARBITER) 2 study.

Seventy-seven subjects were randomized to extended-release niacin (1 g/day) and completed the 12-month endpoint assessment of ARBITER 2. The relationships between self-reported flushing and changes in high-density lipoprotein cholesterol (HDL-C) and change in carotid intima-media thickness (CIMT) at 12 months were evaluated.

Flushing was reported by 53 subjects (68.8%) over 12 months. Mean increases in HDL-C at 12 months were significantly greater among subjects with flushing versus those without flushing (7.3 ± 6.6 vs 4.0 ± 6.9 mg/dL; P < 0.05). On multivariate analysis, HDL-C increase was significantly associated with self-reported flushing, controlling for age, gender, diabetes, baseline HDL-C and triglycerides, aspirin use, and medication adherence (P = 0.019). There was a nonsignificant trend for less progression of CIMT among subjects with flushing (0.011 ± 0.012 vs 0.033 ± 0.026 mm; P = 0.38). Medication adherence assessed by pill counts was high and was similar among those with (90%) and without (92%) flushing.

In the ARBITER 2 trial, niacin-induced flushing was independently associated with a greater HDL-C response and with a directional trend for slowed CIMT progression.