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Comparative Effects of Lovastatin and Niacin in Primary Hypercholesterolemia: A Prospective Trial

Comparative Effects of Lovastatin and Niacin in Primary Hypercholesterolemia: A Prospective Trial Abstract Background: Niacin and lovastatin are both effective drugs for the treatment of hypercholesterolemia and are among the drugs of first choice recommended by the adult treatment panel. To date, however, no studies have directly compared the lipoprotein-modifying effects and safety of lovastatin and niacin across their usual dosage range in patients with primary hypercholesterolemia. Methods: The efficacy and safety of lovastatin and niacin were compared in a controlled, randomized, open-label study of 26 weeks' duration that was conducted at five lipid clinics. One hundred thirty-six patients with primary hypercholesterolemia participated in the study. Entry criteria were a low-density lipoprotein (LDL) cholesterol level greater than 4.37 mmol/L (160 mg/dL) with coronary heart disease and/or more than two coronary heart disease risk factors or an LDL cholesterol level greater than 5.19 mmol/L (190 mg/dL) in patients without coronary heart disease or less than two coronary heart disease risk factors. The study consisted of a 4-week diet run-in period after which eligible patients were randomly assigned to receive treatment with either lovastatin (20 mg/d) or niacin (1.5 g/d) for 10 weeks. On the basis of the LDL cholesterol response and patient tolerance, the doses were sequentially increased to 40 and 80 mg/d of lovastatin or 3 and 4.5 g/d of niacin after 10 and 18 weeks of treatment, respectively. Results: In the two patient groups, 66% of patients treated with lovastatin and 54% of patients treated with niacin underwent full dosage titration. At all time points, lovastatin was significantly (P<.01) more effective than niacin in reducing LDL cholesterol levels (26% vs 5% at week 10, 28% vs 16% at week 18, and 32% vs 23% at week 26), whereas niacin was more effective (P<.01) in increasing high-density lipoprotein cholesterol levels (6% vs 20% at week 10, 8% vs 29% at week 18, and 7% vs 33% at week 26). Niacin reduced Lp(a) lipoprotein levels by 35% at week 26, whereas lovastatin had no effect. Cutaneous flushing was the most common side effect during treatment with niacin. Conclusions: Lovastatin and niacin both exerted favorable dose-dependent changes on the concentrations of plasma lipids and lipoproteins. Lovastatin was more effective in reducing LDL cholesterol concentrations, whereas niacin was more effective in increasing high-density lipoprotein cholesterol concentrations and reducing the Lp(a) lipoprotein level. Lovastatin was better tolerated than niacin, in large part because of the common cutaneous side effects of niacin.(Arch Intern Med. 1994;154:1586-1595) References 1. Figge HL, Figge J, Souney PF, Mutnick AH, Sacks F. Nicotinic acid: a review of its use in the treatment of lipid disorders . Pharmacotherapy . 1988;8:287-294. 2. Grundy SM. HMG-CoA reductase inhibitors for the treatment of hypercholesterolemia . N Engl J Med . 1988;319:24-32.Crossref 3. Gurakar A, Hoeg JM, Kostner G, Papadopoulos NM, Brewer HB Jr. Levels of lipoprotein(a) Lp(a) decline with neomycin and niacin treatment . Atherosclerosis . 1985;57:293-301.Crossref 4. Carlson LA, Hamsten A, Asplund A. Pronounced lowering of serum levels of lipoprotein(a) Lp(a) in hyperlipidemic subjects treated with nicotinic acid . J Intern Med . 1989;226:271-276.Crossref 5. Scanu AM, Fless GM. Lipoprotein(a) heterogeneity and biological relevance . J Clin Invest . 1990;85:1709-1715.Crossref 6. Scanu AM. Lipoprotein(a): a genetic risk factor for premature coronary heart disease . JAMA . 1992;267:3326-3329.Crossref 7. Seed M, Hoppichler F, Reaveley D, et al. Relation of serum lipoprotein(a) concentration and apolipoprotein(a) phenotype to coronary heart disease in patients with familial hypercholesterolemia . N Engl J Med . 1990;322:1494-1499.Crossref 8. Ridker PM, Hennekens CH, Stampfer MJ. A prospective study of lipoprotein(a) and the risk of myocardial infarction . JAMA . 1993;270:2195-2199.Crossref 9. Recommendations for treatment of hyperlipidemia in adults: a joint statement of the Nutrition Committee and the Council on Arteriosclerosis . Circulation . 1984;69:1067A-1090A. 10. Report of the National Cholesterol Education Program expert panel on detection, evaluation, and treatment of high blood cholesterol in adults . Arch Intern Med . 1988;148:36-69.Crossref 11. Harris WS, Held JD, Dujovne CA. The dietary RISCC rating: a novel method to assess the hyperlipidemic potential of a diet . Arterioscler Thromb . 1988;8: 633. Abstract. 12. Lipid Research Clinics Program. Manual of Laboratory Operations: Lipid and Lipoprotein Analysis . Washington, DC: US Dept of Health Education and Welfare; 1982. Publication NIH 75-628. 13. Warnick GR, Albers JJ. A comprehensive evaluation of the heparin manganese precipitation procedure for estimating high-density lipoprotein cholesterol . J Lipid Res . 1978;19:65-76. 14. Stein EA, DiPersio L, Pesce AJ, et al. Enzyme-linked immunoabsorbent assay of apolipoprotein A-II in plasma using a monoclonal antibody . Clin Chem . 1986; 32:967-971. 15. Stein EA, Kreisberg R, Miller V, et al. Effect of simvastatin and cholestyramine in familial and nonfamilial hypercholesterolemia . Arch Intern Med . 1990;150: 341-345.Crossref 16. Miller JA, Stein EA, Kaplan LA. Development of a competitive binding enzyme-linked immunoabsorbent assay (ELISA) for plasma apoprotein E using a monoclonal antibody (Mab) . Clin Chem . 1990;36:964. 17. Stein EA, Kumbla L, Miller J, Srivastiva L, Kashyap ML. Development and evaluation of a competitive ELISA for Lp(a) . Clin Chem . 1992;38:1067. 18. Puri ML. Combining independent one sample tests of significance . Ann Inst Stat Math . 1967;19:285-300.Crossref 19. Klotz JH. The Wilcoxon, ties, and the computer . J Am Stat Assoc . 1966;61: 772-787.Crossref 20. Bradford RH, Shear CL, Chremos AN, et al. Expanded clinical evaluation of lovastatin (EXCEL) study results . Arch Intern Med . 1991;151:43-49.Crossref 21. Shepherd J, Packard CJ, Patsch JR, Gotto AM, Taunton D. Effects of nicotinic acid therapy on plasma high density lipoprotein subfraction distribution and composition and on apolipoprotein A metabolism . J Clin Invest . 1979;63:858-867.Crossref 22. Wahlberg G, Walldius G, Olsson AG, Kirstein P. Effects of nicotinic acid on serum cholesterol concentrations of high density lipoprotein subfractions HDL2 and HDL3 in hyperlipoproteinaemia . J Intern Med . 1990;228:151-157.Crossref 23. Johansson J, Carlson LA. The effects of nicotinic acid treatment on high density lipoprotein particle size subclass levels in hyperlipidaemic subjects . Atherosclerosis . 1990;83:207-216.Crossref 24. Knopp RH, Ginsberg J, Albers JJ, et al. Contrasting effects of unmodified and time-release forms of niacin on lipoproteins in hyperlipidemic subjects: clues to mechanism of action of niacin . Metabolism . 1985;32:642-650.Crossref 25. Helve E, Tikkanen MJ. Comparison of lovastatin and probucol in treatment of familial and non-familial hypercholesterolemia: different effects on lipoprotein profiles . Atherosclerosis . 1988;72:189-197.Crossref 26. The Lovastatin Pravastatin Study Group. A multicenter comparative trial of lovastatin and pravastatin in the treatment of hypercholesterolemia . Am J Cardiol . 1993;71:810-815.Crossref 27. Seed M, Perombelon N, O'Connor B, Reaveley D, Knight B. The effect of nicotinic acid and acipimox on Lp(a) concentration and turnover . Presented at Drugs Affecting Lipid Metabolism; September 15, 1992 ; Florence, Italy. 28. Saito Y, Yoshita S, Nakaya N, Hata Y, Goto Y. Comparison between morning and evening doses of simvastatin in hyperlipidemic subjects: a double-blind comparative study . Arterioscler Thromb . 1991;11:816-826.Crossref 29. Patterson DJ, Dew EW, Gyorkey F, Graham DY. Niacin hepatitis . South Med J . 1983;76:239-241.Crossref 30. Christensen NA, Achor RW, Berge KG, Mason HL. Nicotinic acid treatment of hypercholesterolemia, comparison of plain and sustained action preparations, and report of two cases of jaundice . JAMA . 1961;177:546-550.Crossref 31. Mullin GE, Greenson JK, Mitchell MC. Fulminant hepatic failure after ingestion of sustained-release nicotinic acid . Ann Intern Med . 1989;111:253-255.Crossref 32. Blankenhorn DH, Nessim SA, Johnson RL, Sanmarco ME, Azen SP, Cashin-Hemphill L. Beneficial effects of combined colestipol-niacin therapy on coronary atherosclerosis and coronary venous bypass grafts . JAMA . 1987;257: 3233-3240.Crossref 33. Brown G, Albers JJ, Fischer LD, et al. Regression of coronary artery disease as a result of intensive lipid-lowering therapy in men with high levels of apolipoprotein B . N Engl J Med . 1990;330:1291-1298. 34. The Coronary Drug Project Research Group. Clofibrate and niacin in coronary heart disease . JAMA . 1975;231:360-381.Crossref 35. Canner PL, Berge KG, Wenger NK, et al. Fifteen year mortality in coronary drug project patients: long-term benefit with niacin . J Am Coll Cardiol . 1986; 8:1245-1255.Crossref 36. Luria MH. Effect of low-dose niacin on high-density lipoprotein cholesterol and total cholesterol/high-density lipoprotein cholesterol ratio . Arch Intern Med . 1988;148:2943-2945.Crossref 37. Squires RW, Allison TG, Gau GT, Miller TD, Kottke BA. Low-dose, time-release nicotinic acid: effects in selected patients with low concentrations of high density lipoprotein cholesterol . Mayo Clin Proc . 1992;67:855-860.Crossref 38. Alderman JD, Pasternak RC, Sacks FM, Smith HS, Monrad ES, Grossman W. Effect of a modified, well-tolerated niacin regimen on serum total cholesterol, high density lipoprotein cholesterol and the cholesterol to high density lipoprotein ratio . Am J Cardiol . 1989;64:725-729.Crossref 39. Lepre F, Campbell B, Crane S, Hickman P. Low-dose sustained-release nicotinic acid (Tri-B3) and lipoprotein(a) . Am J Cardiol . 1992;70:133.Crossref 40. Parsons WB. Studies of nicotinic acid in hypercholesterolemia: changes in hepatic function, carbohydrate tolerance and uric acid metabolism . Arch Intern Med . 1961;107:653-667.Crossref 41. Blankenhorn DH, Azen SP, Kramsch DC, et al. Coronary angiographic changes with lovastatin therapy: the Monitored Atherosclerosis Regression Study (MARS) . Ann Intern Med . 1993;119:969-976.Crossref 42. Davey-Smith G, Song F, Sheldon TA. Cholesterol-lowering and mortality: the importance of considering initial level of risk . BMJ . 1993;306:1367-1373.Crossref http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Internal Medicine American Medical Association

Comparative Effects of Lovastatin and Niacin in Primary Hypercholesterolemia: A Prospective Trial

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Publisher
American Medical Association
Copyright
Copyright © 1994 American Medical Association. All Rights Reserved.
ISSN
0003-9926
eISSN
1538-3679
DOI
10.1001/archinte.1994.00420140051007
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Abstract

Abstract Background: Niacin and lovastatin are both effective drugs for the treatment of hypercholesterolemia and are among the drugs of first choice recommended by the adult treatment panel. To date, however, no studies have directly compared the lipoprotein-modifying effects and safety of lovastatin and niacin across their usual dosage range in patients with primary hypercholesterolemia. Methods: The efficacy and safety of lovastatin and niacin were compared in a controlled, randomized, open-label study of 26 weeks' duration that was conducted at five lipid clinics. One hundred thirty-six patients with primary hypercholesterolemia participated in the study. Entry criteria were a low-density lipoprotein (LDL) cholesterol level greater than 4.37 mmol/L (160 mg/dL) with coronary heart disease and/or more than two coronary heart disease risk factors or an LDL cholesterol level greater than 5.19 mmol/L (190 mg/dL) in patients without coronary heart disease or less than two coronary heart disease risk factors. The study consisted of a 4-week diet run-in period after which eligible patients were randomly assigned to receive treatment with either lovastatin (20 mg/d) or niacin (1.5 g/d) for 10 weeks. On the basis of the LDL cholesterol response and patient tolerance, the doses were sequentially increased to 40 and 80 mg/d of lovastatin or 3 and 4.5 g/d of niacin after 10 and 18 weeks of treatment, respectively. Results: In the two patient groups, 66% of patients treated with lovastatin and 54% of patients treated with niacin underwent full dosage titration. At all time points, lovastatin was significantly (P<.01) more effective than niacin in reducing LDL cholesterol levels (26% vs 5% at week 10, 28% vs 16% at week 18, and 32% vs 23% at week 26), whereas niacin was more effective (P<.01) in increasing high-density lipoprotein cholesterol levels (6% vs 20% at week 10, 8% vs 29% at week 18, and 7% vs 33% at week 26). Niacin reduced Lp(a) lipoprotein levels by 35% at week 26, whereas lovastatin had no effect. Cutaneous flushing was the most common side effect during treatment with niacin. Conclusions: Lovastatin and niacin both exerted favorable dose-dependent changes on the concentrations of plasma lipids and lipoproteins. Lovastatin was more effective in reducing LDL cholesterol concentrations, whereas niacin was more effective in increasing high-density lipoprotein cholesterol concentrations and reducing the Lp(a) lipoprotein level. Lovastatin was better tolerated than niacin, in large part because of the common cutaneous side effects of niacin.(Arch Intern Med. 1994;154:1586-1595) References 1. Figge HL, Figge J, Souney PF, Mutnick AH, Sacks F. Nicotinic acid: a review of its use in the treatment of lipid disorders . Pharmacotherapy . 1988;8:287-294. 2. Grundy SM. HMG-CoA reductase inhibitors for the treatment of hypercholesterolemia . N Engl J Med . 1988;319:24-32.Crossref 3. Gurakar A, Hoeg JM, Kostner G, Papadopoulos NM, Brewer HB Jr. Levels of lipoprotein(a) Lp(a) decline with neomycin and niacin treatment . Atherosclerosis . 1985;57:293-301.Crossref 4. Carlson LA, Hamsten A, Asplund A. Pronounced lowering of serum levels of lipoprotein(a) Lp(a) in hyperlipidemic subjects treated with nicotinic acid . J Intern Med . 1989;226:271-276.Crossref 5. Scanu AM, Fless GM. Lipoprotein(a) heterogeneity and biological relevance . J Clin Invest . 1990;85:1709-1715.Crossref 6. Scanu AM. Lipoprotein(a): a genetic risk factor for premature coronary heart disease . JAMA . 1992;267:3326-3329.Crossref 7. Seed M, Hoppichler F, Reaveley D, et al. Relation of serum lipoprotein(a) concentration and apolipoprotein(a) phenotype to coronary heart disease in patients with familial hypercholesterolemia . N Engl J Med . 1990;322:1494-1499.Crossref 8. Ridker PM, Hennekens CH, Stampfer MJ. A prospective study of lipoprotein(a) and the risk of myocardial infarction . JAMA . 1993;270:2195-2199.Crossref 9. Recommendations for treatment of hyperlipidemia in adults: a joint statement of the Nutrition Committee and the Council on Arteriosclerosis . Circulation . 1984;69:1067A-1090A. 10. Report of the National Cholesterol Education Program expert panel on detection, evaluation, and treatment of high blood cholesterol in adults . Arch Intern Med . 1988;148:36-69.Crossref 11. Harris WS, Held JD, Dujovne CA. The dietary RISCC rating: a novel method to assess the hyperlipidemic potential of a diet . Arterioscler Thromb . 1988;8: 633. Abstract. 12. Lipid Research Clinics Program. Manual of Laboratory Operations: Lipid and Lipoprotein Analysis . Washington, DC: US Dept of Health Education and Welfare; 1982. Publication NIH 75-628. 13. Warnick GR, Albers JJ. A comprehensive evaluation of the heparin manganese precipitation procedure for estimating high-density lipoprotein cholesterol . J Lipid Res . 1978;19:65-76. 14. Stein EA, DiPersio L, Pesce AJ, et al. Enzyme-linked immunoabsorbent assay of apolipoprotein A-II in plasma using a monoclonal antibody . Clin Chem . 1986; 32:967-971. 15. Stein EA, Kreisberg R, Miller V, et al. Effect of simvastatin and cholestyramine in familial and nonfamilial hypercholesterolemia . Arch Intern Med . 1990;150: 341-345.Crossref 16. Miller JA, Stein EA, Kaplan LA. Development of a competitive binding enzyme-linked immunoabsorbent assay (ELISA) for plasma apoprotein E using a monoclonal antibody (Mab) . Clin Chem . 1990;36:964. 17. Stein EA, Kumbla L, Miller J, Srivastiva L, Kashyap ML. Development and evaluation of a competitive ELISA for Lp(a) . Clin Chem . 1992;38:1067. 18. Puri ML. Combining independent one sample tests of significance . Ann Inst Stat Math . 1967;19:285-300.Crossref 19. Klotz JH. The Wilcoxon, ties, and the computer . J Am Stat Assoc . 1966;61: 772-787.Crossref 20. Bradford RH, Shear CL, Chremos AN, et al. Expanded clinical evaluation of lovastatin (EXCEL) study results . Arch Intern Med . 1991;151:43-49.Crossref 21. Shepherd J, Packard CJ, Patsch JR, Gotto AM, Taunton D. Effects of nicotinic acid therapy on plasma high density lipoprotein subfraction distribution and composition and on apolipoprotein A metabolism . J Clin Invest . 1979;63:858-867.Crossref 22. Wahlberg G, Walldius G, Olsson AG, Kirstein P. Effects of nicotinic acid on serum cholesterol concentrations of high density lipoprotein subfractions HDL2 and HDL3 in hyperlipoproteinaemia . J Intern Med . 1990;228:151-157.Crossref 23. Johansson J, Carlson LA. The effects of nicotinic acid treatment on high density lipoprotein particle size subclass levels in hyperlipidaemic subjects . Atherosclerosis . 1990;83:207-216.Crossref 24. Knopp RH, Ginsberg J, Albers JJ, et al. Contrasting effects of unmodified and time-release forms of niacin on lipoproteins in hyperlipidemic subjects: clues to mechanism of action of niacin . Metabolism . 1985;32:642-650.Crossref 25. Helve E, Tikkanen MJ. Comparison of lovastatin and probucol in treatment of familial and non-familial hypercholesterolemia: different effects on lipoprotein profiles . Atherosclerosis . 1988;72:189-197.Crossref 26. The Lovastatin Pravastatin Study Group. A multicenter comparative trial of lovastatin and pravastatin in the treatment of hypercholesterolemia . Am J Cardiol . 1993;71:810-815.Crossref 27. Seed M, Perombelon N, O'Connor B, Reaveley D, Knight B. The effect of nicotinic acid and acipimox on Lp(a) concentration and turnover . Presented at Drugs Affecting Lipid Metabolism; September 15, 1992 ; Florence, Italy. 28. Saito Y, Yoshita S, Nakaya N, Hata Y, Goto Y. Comparison between morning and evening doses of simvastatin in hyperlipidemic subjects: a double-blind comparative study . Arterioscler Thromb . 1991;11:816-826.Crossref 29. Patterson DJ, Dew EW, Gyorkey F, Graham DY. Niacin hepatitis . South Med J . 1983;76:239-241.Crossref 30. Christensen NA, Achor RW, Berge KG, Mason HL. Nicotinic acid treatment of hypercholesterolemia, comparison of plain and sustained action preparations, and report of two cases of jaundice . JAMA . 1961;177:546-550.Crossref 31. Mullin GE, Greenson JK, Mitchell MC. Fulminant hepatic failure after ingestion of sustained-release nicotinic acid . Ann Intern Med . 1989;111:253-255.Crossref 32. Blankenhorn DH, Nessim SA, Johnson RL, Sanmarco ME, Azen SP, Cashin-Hemphill L. Beneficial effects of combined colestipol-niacin therapy on coronary atherosclerosis and coronary venous bypass grafts . JAMA . 1987;257: 3233-3240.Crossref 33. Brown G, Albers JJ, Fischer LD, et al. Regression of coronary artery disease as a result of intensive lipid-lowering therapy in men with high levels of apolipoprotein B . N Engl J Med . 1990;330:1291-1298. 34. The Coronary Drug Project Research Group. Clofibrate and niacin in coronary heart disease . JAMA . 1975;231:360-381.Crossref 35. Canner PL, Berge KG, Wenger NK, et al. Fifteen year mortality in coronary drug project patients: long-term benefit with niacin . J Am Coll Cardiol . 1986; 8:1245-1255.Crossref 36. Luria MH. Effect of low-dose niacin on high-density lipoprotein cholesterol and total cholesterol/high-density lipoprotein cholesterol ratio . Arch Intern Med . 1988;148:2943-2945.Crossref 37. Squires RW, Allison TG, Gau GT, Miller TD, Kottke BA. Low-dose, time-release nicotinic acid: effects in selected patients with low concentrations of high density lipoprotein cholesterol . Mayo Clin Proc . 1992;67:855-860.Crossref 38. Alderman JD, Pasternak RC, Sacks FM, Smith HS, Monrad ES, Grossman W. Effect of a modified, well-tolerated niacin regimen on serum total cholesterol, high density lipoprotein cholesterol and the cholesterol to high density lipoprotein ratio . Am J Cardiol . 1989;64:725-729.Crossref 39. Lepre F, Campbell B, Crane S, Hickman P. Low-dose sustained-release nicotinic acid (Tri-B3) and lipoprotein(a) . Am J Cardiol . 1992;70:133.Crossref 40. Parsons WB. Studies of nicotinic acid in hypercholesterolemia: changes in hepatic function, carbohydrate tolerance and uric acid metabolism . Arch Intern Med . 1961;107:653-667.Crossref 41. Blankenhorn DH, Azen SP, Kramsch DC, et al. Coronary angiographic changes with lovastatin therapy: the Monitored Atherosclerosis Regression Study (MARS) . Ann Intern Med . 1993;119:969-976.Crossref 42. Davey-Smith G, Song F, Sheldon TA. Cholesterol-lowering and mortality: the importance of considering initial level of risk . BMJ . 1993;306:1367-1373.Crossref

Journal

Archives of Internal MedicineAmerican Medical Association

Published: Jul 25, 1994

References