Effect of Very Low-Dose Niacin on High-Density Lipoprotein in Patients Undergoing Long-Term Statin Therapy

Jennifer Wink, MD, George Giacoppe, MD, FCCP, and James King, MD

Disclosures

American Heart Journal. 2002;143(3) 

In This Article

Abstract and Introduction

Abstract

Background A low level of high-density lipoprotein (HDLC) is a proven risk factor for coronary artery disease. Niacin raises HDLC levels, but it is infrequently used because of its side effect profile. Niacin's side effects are dose related. This study tests the hypothesis that very low —dose niacin, in conjunction with long-term statin therapy, will improve the lipid profile by significantly raising the level of HDLC, with fewer side effects than traditional doses of niacin.
Methods Fifty patients undergoing stable statin therapy for 3 months were blindly randomized to receive either placebo or niacin 50 mg administered by mouth 2 times daily for 3 months. Patients with diabetes and active smokers were excluded. Each patient completed a questionnaire regarding current medical problems, medications, and lifestyle before and after the therapy. Patients were questioned about any possible side effects that occurred during the medication trial. The primary end points were change in HDLC level and patient-reported side effects.
Results Thirty-nine patients completed the study. Very low —dose niacin added to statin therapy increased the mean HDLC, 2.1 mg/dL in niacin group (standard error of the mean, 0.767) versus  —0.56 mg/dL for placebo group (standard error of the mean- .816, P = .0246 by analysis of variance). Five patients receiving niacin, versus 2 patients receiving placebo, had episodes of flushing. No major side effects were noted. No patients stopped the study medication as a result of side effects.
Conclusions The addition of very low —dose niacin to statin therapy increased HDLC cholesterol significantly, while avoiding the side effects that are associated with traditional doses of niacin therapy.

Introduction

It is well established that decreasing low-density lipoprotein (LDL) levels reduces progression of disease, morbidity, and death in patients with coronary artery disease[1] and reduces the incidence of coronary artery disease and total mortality rate in patients with hyperlipidemia.[2,3,4,5] More recently, it has been shown that low levels of high-density lipoprotein (HDLC) have a significant relation to progression of coronary artery disease and death.[6,7,8,9] Isolated low levels of HDLC are common. Up to 50% of patients without a definite indication for cholesterol-lowering medications on the basis of LDL criteria have low levels of HDLC.[10,11,12] In patients with premature coronary artery disease (men younger than age 55, women younger than age 60), low HDLC cholesterol level is the most common lipid abnormality.[13]

Many recent studies indicate that small increases in HDLC can produce significant decreases in myocardial infarction and cardiovascular-related death. Gordon et al[8] analyzed 4 studies and found that a 1-mg/dL increase in HDLC was associated with a decreased risk of coronary artery disease of 2% in men and 3% in women. The Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial (VA-HIT) showed that increasing HDLC by 6% in patients with isolated low HDLC cholesterol decreased heart-related death and nonfatal myocardial infarction with a relative risk reduction of 22%.[7] These patients also had a 30% reduction in triglycerides, which may have contributed to the decrease in morbidity rates. Finally, data from the Helsinki Health Study showed that raising the serum concentration of HDLC was associated with a reduced incidence of coronary artery disease.[2]

Niacin, in patients with hyperlipidemia, has been shown to decrease morbidity and mortality rates.[14] Among the medications used to treat hyperlipidemia, niacin is the most effective at increasing HDLC.[15,16] Concomitant administration of statins and low-dose niacin has been found to be more effective in altering the LDL/HDLC ratio than either drug alone.[26,27,28,29] The doses of niacin used in these studies ranged from 1000 to 3000 mg/d. However, niacin's side effect profile, including flushing, gastrointestinal upset, and liver function testing abnormalities, have limited the use of this drug.

Community-based studies have found that up to 50% of patients taking niacin quit the medication within a year as a result of side effects.[17,18] Niacin decreases LDL in a dose-related, linear fashion above a threshold dose of 1500 mg.[19,20] Its effects on HDLC are apparent at lower doses, with reports of increases ranging from 18% to 29% and with niacin therapy ranging from 750 to 1500 mg/d.[21,22,23,24] Even at a low dose of 500 mg/dL, the drop-out rate was 10%.[25]

This study explores the ability of very low —dose niacin (50 mg administered 2 times daily) to increase HDLC, while avoiding the deleterious side effects that cause noncompliance. No other study has investigated this dosage range. This dose of niacin can be found in high-potency B-vitamin complex tablets.

Comments

3090D553-9492-4563-8681-AD288FA52ACE

processing....