Effects of colestipol-niacin therapy on human femoral atherosclerosis.

Abstract

The 2-year therapy effect on femoral atherosclerosis was evaluated in the Cholesterol Lowering Atherosclerosis Study (CLAS), a randomized, placebo-plus-diet-controlled angiographic trial of colestipol-niacin therapy plus diet in men with previous coronary bypass surgery. Different diet compositions were prescribed to enhance the differential in blood cholesterol responses between the two groups. The annual rate of change in computer-estimated atherosclerosis (CEA), a measure of lumen abnormality, was evaluated between treatment groups. A significant per-segment therapy effect was found in segments with moderately severe atherosclerosis (p less than 0.04) and in proximal segments (p less than 0.02). When segmental CEA measures were combined into a per-patient score using an adaptation of the National Heart, Lung, and Blood Institute scoring procedure, a significant therapy effect was observed (p less than 0.02). Total variance of the annual change rate in CEA was as predicted from pilot studies, but measurement variation was larger. The therapy effect observed in femoral arteries, although significant, was less marked than the strong and consistent benefit previously reported for both native coronary arteries and aortocoronary bypass grafts.

LDL lowering in peripheral arterial disease:are there benefits beyond reducing cardiovascular morbidity and mortality?

“…Nonstatin lipid-lowering therapy has also been shown to be effective in stabilization of femoral artery atherosclerosis measured by angiography in the Cholesterol Lowering Atherosclerosis (CLAS) study in which men with PAD were randomized to placebo or colestipol plus niacin [53]. The CLAS study demonstrated significant lowering of LDL-C, total cholesterol and triglycerides as well as an improvement in HDL-C in the treatment arm compared with the control.…”

The Effect of Lipid Modification on Peripheral Artery Disease after Endovascular Intervention Trial (ELIMIT)

“…9 Previous placebo-controlled studies had shown that niacin increases high-density lipoprotein cholesterol (HDL-C) levels and lowers triglycerides and low-density lipoprotein cholesterol (LDL-C) levels, resulting in an improved atherogenic lipoprotein profile. 14,15 Combination therapy with ezetimibe and statin had previously been shown to result in significantly greater reduction in LDL-C compared with statin alone. 16 However, when ELIMIT was designed it was unknown whether ezetimibe and niacin were additive to standard statin lipid modification therapy in PAD patients.…”

Niacin inhibits skin dendritic cell mobilization in a GPR109A independent manner but has no impact on monocyte trafficking in atherosclerosis

“…When taken in pharmacological doses (>1 gram/day), the nicotinic acid form of niacin modulates plasma lipid profiles including decreasing circulating total cholesterol, plasma LDL, triglycerides, and Lp(a), while increasing plasma HDL (reviewed in (Carlson, 2005; Montecucco et al, 2010) and inhibits lipolysis in adipose tissue (Carlson, 1963; Wahlberg and Walldius, 1993). Clinical trials assessing the cardiovascular benefits of niacin therapy, either alone or in combination with statins or fibrates, demonstrate that high-dose niacin treatment reduces nonfatal acute myocardial infarction (Brown et al, 1990; 1975; Whitney et al, 2005), plaque progression (Blankenhorn et al, 1991; Blankenhorn et al, 1987; Brown et al, 1990; Lee et al, 2009a; Taylor et al, 2009), and overall mortality (Brown et al, 2001; Canner et al, 1986; Carlson and Rosenhamer, 1988; Taylor et al, 2009; 1975; Whitney et al, 2005). Further, niacin therapy can reverse plaque progression in patients with peripheral artery disease and in fact, treatment induces regression in peripheral plaques (Lee et al, 2009b; Ost and Stenson, 1967).…”