New developments in the use of niacin for treatment of hyperlipidemia: New considerations in the use of an old drug

Coronary Artery Disease

Volumn 7, Issue 4, 1996, Pages 321-326

  Crouse III, John R ^a  

^a WAKE FOREST SCHOOL OF MEDICINE   (United States)

Author keywords

bile acid binding resin; combination therapy; coronary artery disease; hyperlipidemia; niacin; reductase inhibitor; toxicity

Indexed keywords

APOLIPOPROTEIN B100; CHOLESTEROL; FLUINDOSTATIN; HIGH DENSITY LIPOPROTEIN CHOLESTEROL; LIPOPROTEIN A; LOW DENSITY LIPOPROTEIN CHOLESTEROL; MEVINOLIN; NICOTINIC ACID; OXIDOREDUCTASE INHIBITOR; PRAVASTATIN; TRIACYLGLYCEROL;

CLINICAL TRIAL; CORONARY ARTERY DISEASE; DRUG EFFICACY; FLUSHING; GOUT; HEART DEATH; HEART INFARCTION; HEART PALPITATION; HUMAN; HYPERLIPIDEMIA; LIVER TOXICITY; PHARMACEUTICS; PHARMACOLOGY; PRIORITY JOURNAL; REVIEW; SUSTAINED RELEASE PREPARATION;

EID: 0029743885     PISSN: 09546928     EISSN: None     Source Type: Journal    
DOI: 10.1097/00019501-199604000-00009     Document Type: Review

References (52)

1. The Coronary Drug Project Research Group: Clofibrate and niacin in coronary heart disease. JAMA 1975, 231:360-381.
2. Canner PL, Berge KG, Wenger NK, Stamler J, Friedman L, Prineas RJ, et al.: Fifteen year mortality in coronary drug project patients: longterm benefit with niacin. J Am Coll Cardiol 1986, 8:1245-1255.
3. Brown G, Zhao X-Q, Sacco DE, Albert JJ: Lipid lowering and plaque regression: new insights into prevention of plaque disruption and clinical events in coronary disease. Circulation 1993, 87:1781-1791. This article summarizes the experience with regard to angiographic progression and regression and clinical events for studies that had been conducted at the time of the review. Evidence is presented for retardation of progression and acceleration of regression, but the clinical effect far outweighs the effect on atherosclerosis progression. This seminal article has prompted re-thinking of the mechanism whereby cholesterol lowering reduces clinical events. New formulations invoke an endothelial stabilizing effect as much as (if not more than) an effect to retard progression of atherosclerosis.
4. Brown G, Albers JJ, Fisher LD, Schaefer SM, Lin J-T, Kaplan C, et al.: Regression of coronary artery disease as a result of intensive lipidlowering therapy in men with high levels of apolipoprotein B. N Engl J Med 1990, 323:1289-1298.
5. Cashin-Hemphill L, Mack WJ, Pogoda JM, Sanmarco ME, Azen SP, Blankenhorn DH: Beneficial effects of colestipol-niacin on coronary atherosclerosis. JAMA 1990, 264:3013-3017.
6. Kane JP, Malloy MJ, Ports TA, Phillips NR, Diehl JC, Havel RJ: Regression of coronary atherosclerosis during treatment of familial hypercholesterolemia with combined drug regimens. JAMA 1990, 264:3007-3012.
7. Haskell WL, Alderman EL, Fair JM, Maron DJ, Mackey SF, Superko R, et al.: Effects of intensive multiple risk factor reduction on coronary atherosclerosis and clinical cardiac events in men and women with coronary artery disease. Circulation 1994, 89:975-990.
8. Grundy SM, Mok HYI, Zech L, Berman M: Influence of nicotinic acid metabolism of cholesterol and triglycerides in man. J Lipid Res 1981, 22:24-36.
9. Blum CB, Levy RI, Eisenberg S, Hall M, Goebel RH, Berman M: High density lipoprotein metabolism in man. J Clin Invest 1977, 60:795-807.
10. McKenney JM, Proctor JD, Harris S, Chinchili VM: A comparison of the efficacy and toxic effects of sustained vs immediate-release niacin in hypercholesterolemic patients. JAMA 1994, 271:672-710. At least partly because there is no patent protection for use of niacin, there has been a paucity of articles even defining as basic a feature of its use as dose-response relationships. This article provides detailed information on this topic, and, in addition, compares effects of the immediate and the sustainedrelease preparations. Furthermore there is an extensive discussion of the toxicity of the agent, prompting editorial comment [JAMA 1994, 271:709-710] and several letters to the editor [JAMA 1994, 272:513-515].
11. McKenney JM, Proctor JD, Harris S, Chinchili VM: A comparison of the efficacy and toxic effects of sustained vs immediate-release niacin in hypercholesterolemic patients. JAMA 1994, 271:672-710. At least partly because there is no patent protection for use of niacin, there has been a paucity of articles even defining as basic a feature of its use as dose-response relationships. This article provides detailed information on this topic, and, in addition, compares effects of the immediate and the sustainedrelease preparations. Furthermore there is an extensive discussion of the toxicity of the agent, prompting editorial comment [JAMA 1994, 271:709-710] and several letters to the editor [JAMA 1994, 272:513-515].
12. McKenney JM, Proctor JD, Harris S, Chinchili VM: A comparison of the efficacy and toxic effects of sustained vs immediate-release niacin in hypercholesterolemic patients. JAMA 1994, 271:672-710. At least partly because there is no patent protection for use of niacin, there has been a paucity of articles even defining as basic a feature of its use as dose-response relationships. This article provides detailed information on this topic, and, in addition, compares effects of the immediate and the sustainedrelease preparations. Furthermore there is an extensive discussion of the toxicity of the agent, prompting editorial comment [JAMA 1994, 271:709-710] and several letters to the editor [JAMA 1994, 272:513-515].
13. Carlson LA, Olsson AG, Ballantyne D: On the rise in low density and high density lipoproteins in response to the treatment of hypertriglyceridaemia in type IV and type V hyperliproteinaemias. Atherosclerosis 1977, 26:603-609. Increases in HDL with reduction of tryglycerides are generally accepted. Not as well known is the effect of tryglyceride lowering to increase the concentration of LDL as well. This 'classic' article describes these effects as patients with hypertriglyceridemia experience reduction of their triglycerides due to treatment with niacin or fibrates.
14. Lavie CJ, Mailander L, Milani RV: Marked benefit with sustained-release niacin therapy in patients with 'isolated' very low levels of high-density lipoprotein cholesterol and coronary artery disease. Am J Cardiol 1992, 69:1083-1085.
15. Squires RW, Allison TG, Gau GT, Miller TD, Kottke BA: Low-dose timerelease nicotinic acid: effects in selected patients with low concentrations of high-density lipoprotein cholesterol. Mayo Clin Proc 1992, 67:855-860.
16. King JM, Crouse JR, Terry JG, Morgan TM, Spray BJ, Miller NE: Evaluation of effects of unmodified niacin on fasting and postprandial plasma lipids in normolipidemic men with hypoalphalipoproteinemia. Am J Med 1994, 97:323-331. Several drugs that alter lipids have been shown to favorably influence the postprandial triglyceride excusion that results from a fatty meal. This study shows that niacin has a beneficial effect on postprandial lipids. Also reviewed in this study are the effects of niacin on lipids and lipoproteins in comparison with a fibrate (gemfibrozil). Niacin has more dramatic effects on both LDL and HDL than the fibrate.
17. Vega GL, Grundy SM: Lipoprotein responses to treatment with lovastatin, gemfibrozil, and nicotinic acid in normolipidemic patients with hypoalphalipoproteinemia. Arch Intern Med 1994, 154:73-82.
18. Kreisberg RA: Low high-density lipoprotein cholesterol: what does it mean, what can we do about it and what should we do about it? Am J Med 1993, 94:1-6.
19. Martin-Jadraque R, Tato F, Mostaza JM, Vega GL, Grundy SM: Effectiveness of low-dose crystalline nicotinic acid in men with low high-density lipoprotein cholesterol levels. Arch Intern Med 1996, 156:1081-1088.
20. Rodriguez CR, Seman LJ, Ordovas JM, Jenner J, Genest MSJ, Wilson PWF, et al.: Lipoprotein(a) and coronary heart disease. Chem Phys Lipids 1994, 67/68:389-398. This is an excellent and up-to-date review of the chemistry, action, and pathophysiology of Lp(a). This lipoprotein species is destined to be heard more from in coming years.
21. Carlson LA, Hamsten A, Asplund A: Pronounced lowering of serum levels of lipoprotein Lp(a) in hyperlipidaemic subjects treated with nicotinic acid. J Intern Med 1989, 226:271-276.
22. Illingworth DR, Stein EA, Mitchel YB, Dujovne CA, Frost PH, Knopp RH, et al.: Comparative effects of lovastatin and nlacin in primary hypercholesterolemia. Arch Intern Med 1994, 154:1586-1560. Niacin favorably influences Lp(a); reductase inhibitors do not. Another agent of considerable interest that also influences Lp(a) is estrogen, and postmenopausal estrogen use is associated with decreased levels of Lp(a), which, in turn, is associated with decreased CAD [see Arch Intern Med 1993, 153:1462-1468 for estrogen and Lp(a), and Arch Intern Med 1990, 150:2557-2562 for the CAD reduction].
23. Illingworth DR, Stein EA, Mitchel YB, Dujovne CA, Frost PH, Knopp RH, et al.: Comparative effects of lovastatin and nlacin in primary hypercholesterolemia. Arch Intern Med 1994, 154:1586-1560. Niacin favorably influences Lp(a); reductase inhibitors do not. Another agent of considerable interest that also influences Lp(a) is estrogen, and postmenopausal estrogen use is associated with decreased levels of Lp(a), which, in turn, is associated with decreased CAD [see Arch Intern Med 1993, 153:1462-1468 for estrogen and Lp(a), and Arch Intern Med 1990, 150:2557-2562 for the CAD reduction].
24. Illingworth DR, Stein EA, Mitchel YB, Dujovne CA, Frost PH, Knopp RH, et al.: Comparative effects of lovastatin and nlacin in primary hypercholesterolemia. Arch Intern Med 1994, 154:1586-1560. Niacin favorably influences Lp(a); reductase inhibitors do not. Another agent of considerable interest that also influences Lp(a) is estrogen, and postmenopausal estrogen use is associated with decreased levels of Lp(a), which, in turn, is associated with decreased CAD [see Arch Intern Med 1993, 153:1462-1468 for estrogen and Lp(a), and Arch Intern Med 1990, 150:2557-2562 for the CAD reduction].
25. Gurakar A, Hoeg JM, Kostner G, Papadopoulos NM, Brewer HB: Levels of lipoprotein Lp(a) decline with neomycin and niacin treatment Atherosclerosis 1985, 57:293-301.
26. Zilversmit DB: Atherogenesis: a postprandial phenomenon. Circulation 1979, 60:473-485. This classic article presented the first rationale for the concept that postprandial lipids might be a risk factor for CAD. It has been followed up on by many publications over the following years.
27. Blankenhom DH, Alaupovic P, Wickham E, Chin HP, Azen SP: Prediction of angiographic change in native human coronary arteries and aortocoronary bypass grafts: lipid and nonlipid factors. Circulation 1990,81:470-476.
28. Hodis HN, Mack WJ, Azen SP, Alaupovic, P, Pogoda JM, LaBree L, et al.: Triglyceride and cholesterol-rich lipoproteins have a differential effect on mild/moderate and severe lesion progression as assessed by quantitative coronary angiography in a controlled trial of lovastatin. Circulation 1994, 90:42-49.
29. Phillips NR, Waters D, Have RJ: Plasma lipoproteins and progression of coronary artery disease evaluated by angiography and clinical events. Circulation 1993, 88:2762-2770.
30. Cohn JS: Postprandial lipid metabolism. Curr Opin Lipidol 1994, 5:185-190.
31. Innerarity TL, Mahley RW, Weisgraber KH, Bersot TP, Krauss RM, Vega GL, et al.: Familial defective apolipoprotein B100: a mutation of apolipoprotein B that causes hypercholesterolemia. J Lipid Res 1990, 31:1337-1349. Description of a genetic disorder not related to hepatic receptor status that results in elevated levels of LDL in the plasma and premature CAD.
32. Schmidt EB, Illingworth DR, Bacon S, Russell SJ, Thatcher SR, Mahley RW, et al.: Hypolipidemic effects of nicotinic acid in patients with familial defective apollpoprotein B-100. Metabolism 1993, 42:137-139. Niacin favorably affects LDL in patients with this disorder; the effect is far greater than in patients with heterozygous familial hypercholesterolemia, suggesting that in a patient with markedly elevated LDL responds dramatically to niacin they may have this disorder.
33. Austin MA, Hokanson JE, Brunzell JD: Characterization of low-density lipoprotein subclasses: methodologic approaches and clinical relevance. Curr Opin Lipidol 1993, 5:395-403. Small dense LDL may be another 'new' risk factor for CAD. It is difficult to disentangle the unique effect of this particle from its many companions, increased triglyceride, decreased HDL, and the manifold accompanying characteristics of 'syndrome X' (insulin resistance, hypertension, abdominal obesity).
34. Superko HR, Krauss RM: Differential effects of nicotinic acid in subjects with different LDL subclass patterns. Atherosclerosis 1992, 95:69-76.
35. Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults: Summary of the second report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation and treatment of high blood cholesterol in adults (Adult Treatment Panel II). JAMA 1993, 269:3015-3023. This is the 'revised' version of the National Cholesterol Education Program Guidelines first published in 1988 [Arch Intern Med 1993, 148:36-69]. Emphasized in the new version are the importance of HDL-C, and the need for very intensive treatment of LDL in patients with prevalent CAD. Essential reading for anyone involved in the treatment of hyperlipidemia.
36. Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults: Summary of the second report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation and treatment of high blood cholesterol in adults (Adult Treatment Panel II). JAMA 1993, 269:3015-3023. This is the 'revised' version of the National Cholesterol Education Program Guidelines first published in 1988 [Arch Intern Med 1993, 148:36-69]. Emphasized in the new version are the importance of HDL-C, and the need for very intensive treatment of LDL in patients with prevalent CAD. Essential reading for anyone involved in the treatment of hyperlipidemia.
37. Vacek JL, Dittmeier G, Chiarelli T, White J, Bell HH: Comparison of lovastatin (20 mg) and nicotinic acid (1.2 g) with either drug alone for type II hyperlipoproteinemia. Am J Cardiol 1995, 76:182-184.
38. O'Keefe JH, Harris WS, Nelson J, Windsor SL: Effects of pravastatin with niacin or magnesium on lipid levels and postprandial lipemia. Am J Cardiol 1995, 76:480-484.
39. Davignon J, Roederer G, Montigny M, Hayden MR, Tan M-H, Connelly PW, et al.: Comparative efficacy and safety of pravastatin, nicotinic acid and the two combined in patients with hypercholesterolemia. Am J Cardiol 1994, 73:339-345.
40. Jacobson TA, Chin MM, Fromell GJ, Jokubaitis LA, Amorosa LF: Fluvastatin with and without niacin for hypercholesterolemia. Am J Cardiol 1994, 74:149-154.
41. Jacobson TA, Jokubaitis LA, Amorosa LF: Fluvastatin and niacin in hypercholesterolemia: a preliminary report on gender differences in efficacy. Am J Med 1994, 96 (suppl 6A):64S-68S.
42. Jacobson TA, Amorosa LF: Combination therapy with fluvastatin and niacin in hypercholesterolemia: a preliminary report on safety. Am J Cardiol 1994, 73:25D-29D.
43. Reaven P, Witztum JL: Lovastatin, nicotinic acid, and rhabdomyolysis [letter]. Ann Intern Med 1988, 109:597-598.
44. Norman DJ, Illingsworth DR, Munson J, Hsenpud J: Myolysis and acute renal failure in a heart-transplant recipient receiving lovastatin [letter]. N Engl J Med 1988, 318:46-47.
45. Henkin Y, Johnson KC, Segrest JP: Rechallenge with crystalline niacin after drug-induced hepatitis from sustained-release niacin. JAMA 1990, 264:241-243.
46. Dalton TA, Berry RS: Hepatotoxicity associated with sustained-release niacin. Am J Med 1991, 93:102-104.
47. Patel SD, Taylor HC: Intrahepatic cholestasis during nicotinic acid therapy. Cleveland Clin J Med 1994, 61:70-75.
48. Gibbons LW, Gonzalez V, Gordon N, Grundy S: The prevalence of side effects with regular and sustained-release nicotinic acid. Am J Med 1995, 99:378-385.
49. Keenan JM, Fontaine PL, Wenz JB, Myers S, Huang Z, Ripein CM: Niacin revisited: a randomized, controlled trial of wax-matrix sustainedrelease niacin in hypercholesterolemia. Arch Intern Med 1991, 151:1424-1432.
50. Keenan JM, Bae C-Y, Fontaine PL, Wenz JB, Myers S, Huang Z, et al.: Treatment of hypercholesterolemia: comparison of younger versus older patients using wax-matrix sustained-release niacin. J Am Geriatr Soc 1992, 40:12-18.
51. Garg A, Grundy SM: Nicotinic acid as therapy for dyslipidemia in non insulin-dependent diabetes mellitus. JAMA 1990, 264:723-726. For fairly obvious reasons there have been few publications on the use of niacin in patients with diabetes mellitus. This publication suggests that the effect of niacin to worsen glucose tolerance is quite real, although there are patients who can tolerate this combination with improvement of their lipid profiles.
52. Schwartz ML: Severe reversible hyperglycemia as a consequence of niacin therapy. Arch Intern Med 1993, 153:2050-2052.