Curr Atheroscler Rep 2001 Jan;3(1):74-82

The benefits of niacin in atherosclerosis.

Tavintharan S, Kashyap ML.

Cholesterol Research Center, Department of Veterans Affairs Healthcare System, University of California, Irvine, 5901 East Seventh Street (11/111-I) Long Beach, CA 90822, USA.

Niacin favorably alters all major lipid subfractions at pharmacologic doses. Alone or in combination, it promotes regression of coronary artery disease, decreases coronary events, stroke, and total mortality. Major recent progress in niacin is in four areas. Firstly, recent data indicate that it increases high-density lipoprotein (HDL) and lowers triglycerides and low-density lipoprotein (LDL) by mechanisms different from statins, fibrates, and bile-sequestrants, giving rationale for combination therapy to achieve synergistic effects for complete lipid goal achievement. Secondly, new data on an extended-release preparation of niacin given once nightly indicates that it is as effective and has greater tolerability than immediate-release niacin. Thirdly, preliminary data with a single tablet formulation extended-release niacin and an HMG CoA reductase inhibitor (lovastatin) shows it to be safe and very effective, especially for raising HDL. Finally, emerging evidence indicates that niacin can be used effectively and safely in patients with type 2 diabetes mellitus, who often have low HDL levels.



---------------------------

Arch Intern Med 2002 Jul 22;162(14):1568-76

Efficacy, safety, and tolerability of once-daily niacin for the treatment of dyslipidemia associated with type 2 diabetes: results of the assessment of diabetes control and evaluation of the efficacy of niaspan trial.

Grundy SM, Vega GL, McGovern ME, Tulloch BR, Kendall DM, Fitz-Patrick D, Ganda OP, Rosenson RS, Buse JB, Robertson DD, Sheehan JP.

The University of Texas Southwestern Medical Center, Room Y3206, 5323 Harry Hines Blvd, Dallas, TX 75390-9052.

BACKGROUND: Diabetic dyslipidemia is characterized by high triglyceride levels; low high-density lipoprotein cholesterol levels; small, dense low-density lipoprotein particles; and high free fatty acid levels. Niacin reduces concentrations of triglyceride-rich and small low-density lipoprotein particles while increasing high-density lipoprotein cholesterol levels. It also lowers levels of free fatty acids and lipoprotein(a). However, the use of niacin in patients with diabetes has been discouraged because high doses can worsen glycemic control. We evaluated the efficacy and safety of once-daily extended-release (ER) niacin in patients with diabetic dyslipidemia. METHODS: During a 16-week, double-blind, placebo-controlled trial, 148 patients were randomized to placebo (n = 49) or 1000 (n = 45) or 1500 mg/d (n = 52) of ER niacin. Sixty-nine patients (47%) were also receiving concomitant therapy with statins. RESULTS: Dose-dependent increases in high-density lipoprotein cholesterol levels (+19% to +24% [P<.05] vs placebo for both niacin dosages) and reductions in triglyceride levels (-13% to -28% [P<.05] vs placebo for the 1500-mg ER niacin) were observed. Baseline and week 16 values for glycosylated hemoglobin levels were 7.13% and 7.11%, respectively, in the placebo group; 7.28% and 7.35%, respectively, in the 1000-mg ER niacin group (P=.16 vs placebo); and 7.2% and 7.5%, respectively, in the 1500-mg ER niacin group (P=.048 vs placebo). Four patients discontinued participation because of inadequate glucose control. Rates of adverse event rates other than flushing were similar for the niacin and placebo groups. Four patients discontinued participation owing to flushing (including 1 receiving placebo). No hepatotoxic effects or myopathy were observed. CONCLUSION: Low doses of ER niacin (1000 or 1500 mg/d) are a treatment option for dyslipidemia in patients with type 2 diabetes.

--------------------

Diabetes Obes Metab 2002 Jul;4(4):255-261

Niacin treatment of the atherogenic lipid profile and Lp(a) in diabetes.
Pan J, Lin M, Kesala R, Van J, Charles M.

Diabetes Research Center, Tustin, CA, and University of California, Irvine, USA.

OBJECTIVE: We tested the hypotheses that niacin is effective for the separate treatments of abnormalities of LDL particle size, HDL2 percentage and Lp(a) without potential negative effects on glycated haemoglobin. RESEARCH DESIGN AND METHODS: The atherogenic lipid profile lipids, such as triglycerides, small, dense LDL cholesterol (LDLc) particle mass, LDL particle size, total HDLc and HDL2 percentage as well as Lp(a), were measured in 42 diabetic patients with abnormalities of LDL particle size, HDL2 percentage and/or Lp(a) levels before and after niacin treatment. LDL particle size and HDL2 were measured using polyacrylamide gradient gel electrophoreses and Lp(a) was measured by enzyme-linked immunoabsorbance assay (ELISA). RESULTS: After niacin treatment, LDL peak particle diameter increased from 252 +/- 7 A to 263 +/- 7 (p < 0.0001), small, dense LDLc particle mass decreased from 27 +/- 11 mg/dL to 15 +/- 4 (p < 0.0001), total HDLc increased from 39 +/- 7 mg/dL to 51 +/- 11 (p < 0.0001), HDL2 as the percentage of total HDLc mass increased from 29 +/- 8% to 45 +/- 10 (p < 0.0001) and Lp(a) decreased from 43 +/- 17 mg/dL to 25 +/- 10 (p < 0.0001). Mean haemoglobin A1c level was improved during treatment from 7.6 +/- 1.8% to 6.5 +/- 1.0 (p < 0.0001) using increased oral agent and insulin treatment doses in more than 90% of the patients. A total of 21% of the patients were unable to tolerate niacin owing to reversible side-effects, and 14% were unable to adhere to the niacin dosing regimen of three times daily. CONCLUSIONS: These data indicate that in diabetic patients, niacin (i) is effective for treating diabetic dyslipidaemias associated with both the atherogenic lipid profile and Lp(a); (ii) must be used with modern and aggressive oral hypoglycaemic agents or insulin treatment; and (iii) is an important drug to treat diabetes dyslipidaemias because of its broad spectrum of effectiveness.

---------------------

Prev Cardiol 2000 Summer;3(3):131-135

The antilipidemic effects of plain and extended-release niacin.

White Robinson A, Sloan HL, Arnold G.

College of Nursing and Allied Health Professions University of Southwestern Louisiana, Lafayette, LA 70504.

The extensive antihyperlipidemic effects of niacin are well known. Cardiac doses of niacin are effective in lowering low density lipoprotein, triglyceride, and lipoprotein(a) levels and in elevating high density lipoprotein levels. Adverse reactions to niacin range from annoying cutaneous flushing to hepatic toxicity . A new extended-release form of niacin (Niaspan) has been found to have relatively mild hepatic effects. Nighttime dosing of Niaspan appears to attenuate cutaneous flushing. Regardless of the form of drug prescribed, patients advised to use niacin should be carefully screened and monitored. Adverse effects of niacin are emphasized because of their particular importance in the provision of primary care. The dosing schedules for both plain niacin and extended-release niacin are discussed. (c) 2000 by CHF, Inc.

---------------------------------

Am J Cardiol 2000 Dec 21;86(12A):51L-56L

Evaluating niacin in its various forms.

Knopp RH.

Division of Metabolism, Endocrinology and Nutrition, Northwest Lipid Research Clinic, University of Washington, Seattle, USA.

Niacin is available in a number of different formulations according to the speed of drug release. The nomenclature is not standardized, and many names are used interchangeably, creating confusion. Formulations that differ in time of release may have different lipid effects and vary in their adverse reaction profiles. Studies comparing immediate-release with various time-release formulations illustrate these variations. Studies have found immediate-release and the intermediate, or extended-release, once-a-day, prescription form of niacin (i.e., Niaspan), to be essentially equivalent with respect to their efficacy in reducing triglycerides and increasing high-density lipoprotein cholesterol (HDL-C). However, there are fewer side effects and better compliance associated with the latter form.

Am J Cardiol 2000 Dec 21;86(12A):46L-50L

Raising high-density lipoprotein cholesterol with niacin and fibrates: a comparative review.

Sprecher DL.

Department of Cardiology, The Cleveland Clinic Foundation, Ohio 44195, USA.

A growing number of trials that used fibrates and niacin alone or in combination with other lipid-altering agents have shown that both these drugs are effective for reducing total cholesterol, low-density lipoprotein cholesterol (LDL-C) and triglycerides, and for increasing high-density lipoprotein cholesterol (HDL-C) levels. These lipid changes are associated with a reduction in events such as fatal and nonfatal myocardial infarction, stroke, and transient ischemic attack. In angiographic trials, they are associated with disease regression, increased minimal luminal diameter, and protection from risk of new lesions. In a head-to-head comparison study, niacin 2,000 mg/day increased HDL-C more than gemfibrozil 1,200 mg/day, and decreased the total cholesterol-to-HDL-C ratio, lipoprotein (a) (Lp[a]), and fibrinogen levels significantly more. Combination therapies of niacin plus a resin or statin are effective, well tolerated, and safe.

---------------

Prog Cardiovasc Nurs 2001 Winter;16(1):14-20

Use of niacin in the prevention and management of hyperlipidemia.
Robinson AW, Sloan HL, Arnold G.

University of Louisana at Lafayette, College of Nursing and Allied Health Professions, PO Box 43810, Lafayette, LA 70504-3810, USA.

Niacin is an inexpensive drug useful in treating various forms of hyperlipidemia. Cardiac doses of niacin are effective in lowering serum triglyceride, low density lipoprotein, and lipoprotein-a levels and in elevating high density lipoprotein levels. Adverse reactions to niacin are varied and dose-dependent and range from annoying cutaneous flushing to hepatic toxicity. Patients advised to use the drug should be carefully screened and monitored. This paper reviews the pathologic and pharmacologic basis for niacin as an antilipemic agent. The biochemical and physiologic effects of the drug and its mechanisms of action are discussed. Emphasis is placed on the importance of aggressive management of serum lipids and the therapeutic uses of niacin. The use of niacin in primary and secondary prevention of heart disease is stressed. A patient education guide is included.