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High-Dose Nicotinic Acid Improves Atherosclerosis
Am Fam Physician. 2010 Feb 1;81(3):340-345.
Background: In patients with atherosclerosis, treatment with statins to decrease low-density lipoprotein (LDL) cholesterol reduces cardiovascular morbidity and mortality. However, statin therapy prevents only a minority of these events. Patients with low levels of high-density lipoprotein (HDL) cholesterol have higher rates of cardiovascular disease independent of their LDL cholesterol levels, indicating a role for increasing HDL. Nicotinic acid raises HDL cholesterol levels by 20 to 25 percent and is the most effective drug available for HDL elevation. Using plaque size measured with magnetic resonance imaging (MRI) to chart progression or regression of atherosclerosis, Lee and colleagues studied the effects of modified-release nicotinic acid on patients with known atherosclerosis and low HDL cholesterol levels, who had achieved LDL cholesterol targets with statin therapy.
The Study: This double-blind, randomized controlled clinical trial included participants whose HDL cholesterol level was less than 40 mg per dL (1.04 mmol per L) in the previous 12 months with carotid atherosclerotic stenosis (30 to 70 percent), peripheral artery disease (ankle-brachial index less than 0.9), or type 2 diabetes with coronary artery disease (diagnosed as more than 50 percent occlusion of a major epicardial vessel on angiography). Criteria for LDL cholesterol were not specified, but all patients received statin therapy through their private physician. Exclusion criteria included contraindication to MRI or nicotinic acid; severe carotid stenosis of more than 70 percent; recent acute coronary syndrome or heart failure; uncontrolled diabetes or triglyceridemia; active peptic ulcer disease; or current therapy with oral nitrates, fibrates, or nicorandil. Patients were randomized to treatment with placebo or nicotinic acid for one year. Doses for each were increased over 12 weeks from the 375-mg starting dose to the 2,000-mg daily dosage for the remainder of the 12 months. Participants were instructed to take the medication at bedtime with aspirin to reduce the potential for flushing. MRI scans were performed at baseline and at six and 12 months, with fasting blood work before each scan. The primary end point was the change in carotid artery wall area at 12 months.
Results: A total of 71 participants were randomized. Baseline characteristics were similar in each group, and both groups had similar medication compliance rates (92 to 93 percent). Seven participants in the nicotinic acid group dropped out because of side effects possibly caused by nicotinic acid; 22 of the 35 patients in the treatment arm and 29 of the 36 patients in the placebo arm completed the study. Statin doses remained the same in both groups during the study period. In the nicotinic acid group, HDL cholesterol increased by 23 percent and LDL cholesterol was reduced by 19 percent at 12 months. Triglyceride, lipoprotein (a), and apolipoprotein B levels were also decreased in the nicotinic acid group compared with placebo. The nicotinic acid group showed greater change in carotid artery wall area by MRI, indicating regression of plaque. During the study period, mild transient elevations in creatine kinase and liver enzyme levels occurred, but were not sustained. The fasting glucose level did not change in either group, but patients in the nicotinic acid group had small but statistically significant increases in A1C levels at six and 12 months.
Conclusion: The authors conclude that adding high-dose nicotinic acid to statins has beneficial effects on lipid profiles and MRI-measured atherosclerotic plaques. Larger studies are needed to determine if these changes translate into fewer coronary vascular events.
AMY CRAWFORD-FAUCHER, MD
Lee JM, et al. Effects of high-dose modified-release nicotinic acid on atherosclerosis and vascular function: a randomized, placebo-controlled, magnetic resonance imaging study. J Am Coll Cardiol. November 3, 2009;54(19):1787–1794.
Copyright © 2010 by the American Academy of Family Physicians.
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