Marked benefit with sustained-release niacin therapy in patients with “isolated” very low levels of high-density lipoprotein cholesterol and coronary artery disease

doi:10.1016/0002-9149(92)90868-Y

The American Journal of Cardiology

Volume 69, Issue 12, 15 April 1992, Pages 1083-1085

https://doi.org/10.1016/0002-9149(92)90868-Y Get rights and content

Abstract

During the past 2 decades, the cholesterol coronary artery disease (CAD) hypothesis has become established with considerable attention being directed toward lipid intervention for primary and secondary coronary prevention.¹ Although the National Cholesterol Education Program has focused mostly on total cholesterol and low-density lipoprotein (LDL) cholesterol in their assessment and treatment recommendations,² recent data from epidemiologic, lipid intervention, coronary angiographic studies, and studies of patients with known severe CAD, suggest that a low level of high-density lipoprotein (HDL) cholesterol is perhaps the strongest lipid risk factor for CAD.^3–6 In fact, a high percentage of patients with CAD have “isolated” low levels of HDL cholesterol.⁴ However, nonpharmacologic and drug treatment of patients with isolated low HDL cholesterol has been disappointing. ^3,7 Since niacin has beneficial effects on reducing total cholesterol, LDL cholesterol and triglycerides, and also increases HDL cholesterol, it improves the lipid profile in most patients with dyslipidemias. However, the efficacy of niacin therapy in patients with very low levels of HDL cholesterol (e.g., <30 mg/dl), and particularly for isolated low HDL cholesterol, is not established. Therefore, we assessed the efficacy of sustained-release niacin therapy in CAD patients with very low levels of HDL cholesterol, including its effectiveness in a subgroup with isolated low HDL cholesterol compared with a subgroup with hypertriglyceridemia.

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Dyslipidemia intervention in metabolic syndrome: Emphasis on improving lipids and clinical event reduction
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Citation Excerpt :
Nevertheless, despite the increases in fasting glucose, the drug-treated patients still had marked improvements in the total metabolic profile and in the prevalence of MetS. Clearly, niacin has by far the greatest improvements in HDL-C, including typically 25% to 30% increase in HDL-C (but > 40% increase in HDL-C can be noted in patients with very low levels of HDL-C, especially when combined with hypertriglyceridemia).22,53 Although niacin is not as potent as fibrates to reduce TGs, still 25% to 30% reductions in TGs are frequently noted with niacin.
The metabolic syndrome is a common disorder characterized by central (especially intra-abdominal) obesity, hypertension, impaired glucose tolerance and atherogenic dyslipidemia (including the combination of hypertriglyceridemia and low levels of high-density lipoprotein cholesterol). in this article, the authors review interventions to improve this lipid profile and potentially reduce the risk of major cardiovascular events in patients with metabolic syndrome.
A "hot" topic in dyslipidemia management-"how to beat a flush": Optimizing Niacin tolerability to promote long-term treatment adherence and coronary disease prevention
2010, Mayo Clinic Proceedings
Niacin is the most effective lipid-modifying agent for raising high-density lipoprotein cholesterol levels, but it also causes cutaneous vasodilation with flushing. To determine the frequency of flushing in clinical trials, as well as to delineate counseling and treatment approaches to prevent or manage flushing, a MEDLINE search was conducted of English-language literature from January 1, 1985, through April 7, 2009. This search used the title keywords niacin or nicotinic acid crossed with the Medical Subject Headings adverse effects and human. Niacin flushing is a receptor-mediated, mainly prostaglandin D₂–driven phenomenon, the frequency, onset, and duration of which are largely determined by the distinct pharmacological and metabolic profiles of different niacin formulations. Subjective assessments include ratings of redness, warmth, itching, and tingling. In clinical trials, most (>60%) niacin users experienced mild or moderate flushing, which tended to decrease in frequency and severity with continued niacin treatment, even with advancing doses. Approximately 5% to 20% of patients discontinued treatment because of flushing. Flushing may be minimized by taking niacin with meals (or at bedtime with a low-fat snack), avoiding exacerbating factors (alcohol or hot beverages), and taking 325 mg of aspirin 30 minutes before niacin dosing. The current review advocates an initially slow niacin dose escalation from 0.5 to 1.0 g/d during 8 weeks and then from 1.0 to 2.0 g in a single titration step (if tolerated). Through effective counseling, treatment prophylaxis with aspirin, and careful dose escalation, adherence to niacin treatment can be improved significantly. Wider implementation of these measures should enable higher proportions of patients to reach sufficient niacin doses over time to prevent cardiovascular events.
The SLIM study: Slo-Niacin® and Atorvastatin Treatment of Lipoproteins and Inflammatory Markers in Combined Hyperlipidemia
2009, Journal of Clinical Lipidology
Citation Excerpt :
In an earlier study, Slo-Niacin® increased HDL-C 3% above control, also in a low-HDL population.21 However, Lavie et al20 found a 30 % HDL increase from baseline in a low-HDL population at an average Slo-Niacin dose of 2.4 g/d in 29 subjects. When Slo- and plain (IR) niacins were compared in a crossover design, respective HDL-C increases were 15% and 25% above a 46.5 mg/dL baseline.19
The combination of niacin and statin has proven value in the management of hyperlipidemia and prevention of heart disease. However, the efficacy of the nonprescription time-release niacin, Slo-Niacin®, is little studied alone and not at all with atorvastatin. We studied Slo-Niacin® and atorvastatin, singly and together, to determine efficacy on the combined abnormalities of triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C).
A total of 42 men and women with LDL-C >130 mg/dL and HDL-C <45 mg/dL (men) or <55 mg/dL (women) were randomized to 3 months of atorvastatin 10 mg/d or incremental doses of Slo-Niacin® to 1500 mg/d. The alternate drug was added in the next 3-month segment. Lipid profiles and transaminases were measured monthly and other measures at baseline and the end of each treatment sequence.
Mean entry lipids (in mg/dL) were as follows: TG 187, LDL-C 171, and HDL-C 39. Mean body mass index was 32.6 kg/m². Monotherapy with Slo-Niacin® decreased median TG 15%, mean LDL-C 12%, and non-HDL-C 15% and increased HDL-C 8%. Atorvastatin decreased median TG 26%, mean LDL-C 36%, and non-HDL-C 36% and increased HDL-C 6%. Combined therapy decreased median TG 33% and mean LDL-C and non-HDL-C each 43%. HDL-C increased 10% (all P < .001). Median remnant-like lipoprotein-C decreased 55%, mean apo-B 40%, median high-sensitivity C-reactive protein 23% (all P < .05), tumor necrosis factor α 12%, and no change in interleukin-6. Mean LDL buoyancy increased 15%, apo-A-I 5%, and median HDL₂-C 20% (all P < .05). ALT decreased with Slo-Niacin® treatment alone compared with atorvastatin and also decreased when Slo-Niacin® was added to atorvastatin. Six subjects dropped out of the study, 3 for niacin-related symptoms.
Slo-Niacin® 1.5 g/d with atorvastatin 10 mg/d improved lipoprotein lipids, apoproteins, and inflammation markers without hepatotoxicity. Slo–Niacin® deserves further study as a cost-effective treatment of hyperlipidemia. (ClinicalTrials.gov Identifier: NCT00194402)
Shedding Light on High-Density Lipoprotein Cholesterol. The Post-ILLUMINATE Era<sup>*</sup>*Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology.
2008, Journal of the American College of Cardiology
Cholesteryl Ester Transfer Protein Inhibition. The Next Frontier in Combating Coronary Artery Disease?<sup>*</sup>*Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology.
2006, Journal of the American College of Cardiology
Importance and management of dyslipidemia in the metabolic syndrome
2005, American Journal of the Medical Sciences
The metabolic syndrome is a common disorder characterized by central obesity, impaired glucose tolerance, hypertension, and atherogenic dyslipidemia (including the combination of hypertriglyceridemia, low levels of high-density lipoprotein cholesterol, and a preponderance of small, dense low-density lipoprotein particles). In this manuscript, we review the pathogenesis and significance of dyslipidemia in the metabolic syndrome, the role of nonpharmacologic therapy with therapeutic lifestyle changes, and drug therapies, including statins, fibrates, nicotinic acid, and omega-3 fatty acids or fish oils, alone or in drug combinations, to improve lipids and reduce the chance of subsequent cardiovascular disease events.

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The American Journal of Cardiology

Abstract

References (11)

Management of lipids in primary and secondary prevention of cardiovascular diseases

National Cholesterol Education Program's recommendations and implications of “missing” high-density lipoprotein cholesterol in cardiac rehabilitation programs

Am J Cardiol

Dyslipidemias with desirable plasma total cholesterol levels and angiographically demonstrated coronary artery disease

Am J Cardiol

The Expert Panel. Report of the National Cholesterol Education Expert Panel on detection, evaluation, and treatment of high blood cholesterol in adults

Arch Intern Med

High-density lipoprotein cholesterol recommendations for routine testing and treatment

Postgrad Med

Cited by (58)

Dyslipidemia intervention in metabolic syndrome: Emphasis on improving lipids and clinical event reduction

A "hot" topic in dyslipidemia management-"how to beat a flush": Optimizing Niacin tolerability to promote long-term treatment adherence and coronary disease prevention

The SLIM study: Slo-Niacin® and Atorvastatin Treatment of Lipoproteins and Inflammatory Markers in Combined Hyperlipidemia

Shedding Light on High-Density Lipoprotein Cholesterol. The Post-ILLUMINATE Era<sup></sup>Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology.

Importance and management of dyslipidemia in the metabolic syndrome

Brief reportMarked benefit with sustained-release niacin therapy in patients with “isolated” very low levels of high-density lipoprotein cholesterol and coronary artery disease

Abstract

Am J Cardiol

Am J Cardiol

The Expert Panel. Report of the National Cholesterol Education Expert Panel on detection, evaluation, and treatment of high blood cholesterol in adults

Arch Intern Med

High-density lipoprotein cholesterol recommendations for routine testing and treatment

Postgrad Med

Brief report
Marked benefit with sustained-release niacin therapy in patients with “isolated” very low levels of high-density lipoprotein cholesterol and coronary artery disease