Benefit on Atherosclerosis of Adding Niacin in Patients With Low HDL‐Cholesterol Taking a Statin

Statins are the drugs of choice for reduction of low-density lipoprotein (LDL) cholesterol, but they have limited efficacy in improving high-density lipoprotein (HDL) cholesterol. Thus, the results of Arterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol (ARBITER-2), which demonstrated that the addition of niacin to a statin could substantially increase HDL-cholesterol and reduce progression of atherosclerosis as indicated by measurement of carotid intima-media thickness, have important implications in patients with low LDL1 on a statin. ARBITER-2 evaluated the addition of niacin in 167 patients with documented coronary artery disease who were already taking a statin and in whom LDL was <130 mg/dL and HDL was <45 mg/dL. Methodology was prospective, randomized, double-blind, and placebo-controlled. Extended-release niacin was initiated at 500 mg/d and increased to 1000 mg/d. The primary end point—carotid intima-media thickness at 1 year—increased in the statin-placebo group (0.044 mm, p<0.001) and did not change significantly in the statin-niacin patients. In the latter group, HDL increased from 39 to 47 mg/dL (p<0.001), triglycerides decreased (164 to 134 mg/dL, p<0.01) and LDL was unchanged from baseline (89 mg/dL). Fasting glucose rose in statin-niacin patients (from 107 to 123 mg/dL, p<0.01), and there was no alteration in C-reactive protein. Lipids were unchanged in the statin-placebo group. Progression of carotid intima-media thickness was least on statin-niacin in patients without diabetes or the metabolic syndrome. Although the study was not powered to detect an effect on cardiovascular events, these occurred in three patients in the statin-niacin arm and seven in the statin-placebo arm. Adherence to therapy was >90% in both arms. There was no myositis or excessive elevation of liver function tests, but the majority of niacin patients experienced flushing. This study extends prior separate reports on the therapeutic potential of niacin and of augmenting HDL and supports the use of niacin in patients with coronary artery disease and low HDL while taking a statin. However, the effect on glucose metabolism during this relatively short-term study raises concern regarding this risk factor during long-term therapy. Further, this investigation does not provide information on the therapeutic potential of further lowering LDL in accord with recently suggested aggressive therapeutic options.