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July 15, 1988, Vol 260, No. 3 >
ARTICLE | July 15, 1988

A Multicenter Comparison of Lovastatin and Cholestyramine Therapy for Severe Primary Hypercholesterolemia FREE

[+] Author Affiliations

Reprint requests to Merck Sharp & Dohme Research Laboratories, Rahway, NJ 07065 (Jonathan A. Tobert, MB, PhD).


JAMA. 1988;260(3):359-366. doi:10.1001/jama.1988.03410030075032
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References

This study compares lovastatin and cholestyramine resin therapy in patients with severe primary hypercholesterolemia. Two hundred sixty-four patients on lipid-lowering diets were randomized equally to receive 12 g of cholestyramine resin, 20 mg of lovastatin, or 40 mg of lovastatin, each twice a day. The mean reductions among the three groups after 12 weeks' treatment in levels of total plasma cholesterol (-17%, -27%, and -34%, respectively) and low-density lipoprotein cholesterol ( - 23%, - 32%, and - 42%, respectively) and the median reductions in apolipoprotein B levels (-21%, -28%, and -33%, respectively) were all significantly different between groups. Similar mean increases in high-density lipoprotein cholesterol levels (8%, 9%, and 8%, respectively) and median increases in apolipoprotein A-I levels (7%, 6%, and 11%, respectively) were observed in all treatment groups. Cholestyramine resin treatment had no significant effect on very low-density lipoprotein cholesterol and apolipoprotein A-ll levels and produced a median 11% increase in plasma triglyceride concentration; in contrast, administration of either 20 or 40 mg of lovastatin twice a day was associated with median reductions in very low-density lipoprotein cholesterol levels (-34% and -31%, respectively) and plasma triglyceride levels ( - 21% and - 27%, respectively) and median increases in levels of apolipoprotein A-ll (8% and 13%, respectively). Adverse events in all treatment groups were preponderantly in the gastrointestinal tract; gastrointestinal tract symptoms that could be attributed to therapy with a specific drug occurred in 58% of the cholestyramine resin group, 13% of the 20-mg lovastatin group, and 14% of the 40-mg lovastatin group. The only drug-attributable serious adverse event was a reversible myopathy in a patient taking 40 mg of lovastatin twice a day. We conclude that lovastatin is both more effective and better tolerated than cholestyramine resin in the treatment of primary hypercholesterolemia.

(JAMA 1988;260:359-366)

REFERENCES

1 +
 Lowering blood cholesterol to prevent heart disease . JAMA 1985;;253:2080-2086.
2 +
 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.
3 +
Connor WE, Connor SL:  The dietary treatment of hyperlipidemia: Rationale, technique, and efficacy . Med Clin North Am 1982;;66:485-518.
4 +
Alberts AW, Chen J, Kuron G, et al:  Mevinolin: A highly-potent competitive inhibitor of hydroxymethylglutaryl-coenzyme A reductase and a cholesterol-lowering agent . Proc Natl Acad Sci USA 1980;;77:3957-3961.
5 +
Brown MS, Goldstein JL:  Drugs used in the treatment of hyperlipoproteinemias , in Gilman AG, Goodman LS, Rall TW, et al (eds): The Pharmacological Basis of Therapeutics . New York, Macmillan Publishing Co Inc, 1985;, pp 827-845.
6 +
Lipid Research Clinics Program:  The Lipid Research Clinics Coronary Primary Prevention Trial results: I. Reduction in incidence of coronary heart disease . JAMA 1984;;251:351-364.
7 +
Lipid Research Clinics Program:  The Lipid Research Clinics Coronary Primary Prevention Trial results: II. The relationship of reduction in incidence of coronary heart disease to cholesterol lowering . JAMA 1984;;251:365-374.
8 +
Illingworth DR, Sexton GJ:  Hypercholesterolemic effects of mevinolin in patients with heterozygous familial hypercholesterolemia . J Clin Invest 1984;;74:1972-1978.
9 +
Hoeg JM, Maher MB, Zech LA, et al:  Effectiveness of mevinolin on plasma lipoprotein concentration in type II hyperlipoproteinemia . Am J Cardiol 1986;;57:933-939.
10 +
Lovastatin Study Group II:  Therapeutic response to lovastatin (mevinolin) in nonfamilial hypercholesterolemia . JAMA 1986;;256:2829-2834.
11 +
Havel RJ, Hunninghake DB, Illingworth DR, et al:  Lovastatin (mevinolin) in the treatment of heterozygous familial hypercholesterolemia: A multicenter study . Ann Intern Med 1987;;107:609-615.
12 +
Fredrickson DS, Levy RI, Lees RS:  Fat transport in lipoproteins: An integrated approach to mechanism and disorders . N Engl J Med 1967;;276:34-44, 93-103,148-156,215-225,273-281.
13 +
Lipid Research Clinics Program: Manual of Laboratory Operations: Lipid and Lipoprotein Analysis , US Dept of Health, Education, and Welfare publication (NIH) 75:628. Bethesda, Md, National Institutes of Health, 1982;.
14 +
Warnick GR, Albers JJ:  A comprehensive evaluation of the heparin manganese precipitation procedure for estimating high-density lipoprotein cholesterol . J Lipid Res 1978;;19:65-73.
15 +
Mendoza SG, Zerpa A, Carrasco H, et al:  Estradiol, testosterone, apolipoproteins, lipoprotein cholesterol, and lipolytic enzymes in men with premature myocardial infarction and angiographically assessed coronary occlusion . Artery 1983;;12:1-23.
16 +
Stein EA, Dipersio L, Pesce AJ, et al:  Enzymelinked immunoabsorbent assay of apolipoprotein All in plasma, with use of a monoclonal antibody . Clin Chem 1986;;32:967-971.
17 +
Young SG, Smith RS, Hogle DM, et al:  Two new monoclonal antibody-based enzyme-linked assays of apolipoprotein B . Clin Chem 1986;;32:1484-1490.
18 +
Yanagawa T, Kasagi F, Yoshimura T:  A method for estimating incidence rates of onchocerciasis from skin-snip biopsies with consideration of false negatives . Biometrics 1984;;40:301-311.
19 +
Puri ML:  Combining independent one-sample tests of significance . Ann Inst Stat Math 1967;;19:285-300.
20 +
Castelli W, Abbott R, McNamara P:  Summary estimates of cholesterol used to predict coronary heart disease . Circulation 1983;;67:730-734.
21 +
Grundy SM, Ahrens EH Jr, Salen GT:  Interruption of the enterohepatic circulation of bile acids in man: Comparative effects of cholestyramine and ideal exclusion of cholesterol metabolism . J Lab Clin Med 1971;;78:94-121.
22 +
Back P, Hamprecht B, Lynen F:  Regulation of cholesterol biosynthesis in rat liver: Diurnal changes in activity and influence of bile acids . Arch Biochem Biophys 1969;;133:11-21.
23 +
Beil U, Crouse JR, Einarsson K, et al:  Effects on interruption of the enterohepatic circulation of bile acids on the transport of very low-density lipoprotein triglycerides . Metabolism 1982;;31:438-444.
24 +
Witztum JL, Schonfeld G, Wiedman SW, et al:  Bile sequestrant therapy alters the composition of low-density and high-density lipoproteins . Metabolism 1979;;28:221-229.
25 +
Shepherd J, Packard CJ, Bicker S, et al:  Cholestyramine promotes receptor-mediated low-density lipoprotein catabolism . N Engl J Med 1980;; 302:1219-1222.
26 +
Durrington P, Bolton C, Hartog M:  Serum and lipoprotein apolipoprotein B levels in normal subjects and patients with hyperlipoproteinaemia . Clin Chem Acta 1978;;82:151-160.
27 +
Young SG, Witztum JL, Casal DC, et al:  Conservation of the low-density lipoprotein receptorbinding domain of apolipoprotein B . Arteriosclerosis 1986;;6:178-188.
28 +
Bilheimer DW, Grundy SM, Brown MS, et al:  Mevinolin and colestipol stimulate receptor-mediated clearance of low-density lipoprotein from plasma in familial hypercholesterolemia heterozygotes . Proc Natl Acad Sci USA 1983;;80:4124-4128.
29 +
Ma PT, Gil G, Sudhof TC, et al:  Mevinolin, an inhibitor of cholesterol synthesis, induces mRNA for low-density lipoprotein receptor in livers of hamsters and rabbits . Proc Natl Acad Sci USA 1986;;83:8370-8374.
30 +
Grundy SM, Vega GL:  Influence of mevinolin on metabolism of low-density lipoproteins in primary moderate hypercholesterolemia . J Lipid Res 1985;;26:1464-1475.
31 +
Tobert JA:  New developments in lipid-lowering therapy: The role of inhibitors of HMG-CoA reductase . Circulation 1987;;76:534-538.
32 +
Norman DJ, Illingworth DR, Munson J, et al:  Myolysis and acute renal failure in a heart-transplant patient receiving lovastatin . N Engl J Med 1988;;318:46-47.
33 +
East C, Alvizatos PA, Grundy SM, et al:  Rhabdomyolysis in patients receiving lovastatin after cardiac transplantation . N Engl J Med 1988;;318:4748.
34 +
Tobert JA:  Reply . N Engl J Med 1988;;318:48.
35 +
Hunninghake DB, Miller VT, Goldberg I, et al:  Lovastatin: Follow-up ophthalmologic data . JAMA 1988;;259:354-355.
36 +
Blankenhorn DH, Nessim SA, Johnson RL, et al:  Beneficial effects of combined colestipol-niacin therapy on coronary atherosclerosis and coronary venous bypass grafts . JAMA 1987;;257:3233-3240.
37 +
Canner PL, Berg KG, Wenger NK, et al:  Fifteen years mortality in coronary drug project patients: Long-term benefit with niacin . J Am Coll Cardiol 1986;;8:1245-1255.
38 +
Frick MH, Elo O, Haapa K, et al:  Helsinki heart study: Primary prevention trial with gemfibrozil in middle-aged men with dyslipidemia . N Engl J Med 1987;;317:1237-1245.
39 +
Tyroler HA:  Review of lipid-lowering clinical trials in relation to observational epidemiological studies . Circulation 1987;;76:515-522.
40 +
Illingworth DR:  Long-term administration of lovastatin in the treatment of hypercholesterolemia . Eur Heart J 1987;;8( (suppl E) ):103-111.

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Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature

Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal

1 +
 Lowering blood cholesterol to prevent heart disease . JAMA 1985;;253:2080-2086.
2 +
 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.
3 +
Connor WE, Connor SL:  The dietary treatment of hyperlipidemia: Rationale, technique, and efficacy . Med Clin North Am 1982;;66:485-518.
4 +
Alberts AW, Chen J, Kuron G, et al:  Mevinolin: A highly-potent competitive inhibitor of hydroxymethylglutaryl-coenzyme A reductase and a cholesterol-lowering agent . Proc Natl Acad Sci USA 1980;;77:3957-3961.
5 +
Brown MS, Goldstein JL:  Drugs used in the treatment of hyperlipoproteinemias , in Gilman AG, Goodman LS, Rall TW, et al (eds): The Pharmacological Basis of Therapeutics . New York, Macmillan Publishing Co Inc, 1985;, pp 827-845.
6 +
Lipid Research Clinics Program:  The Lipid Research Clinics Coronary Primary Prevention Trial results: I. Reduction in incidence of coronary heart disease . JAMA 1984;;251:351-364.
7 +
Lipid Research Clinics Program:  The Lipid Research Clinics Coronary Primary Prevention Trial results: II. The relationship of reduction in incidence of coronary heart disease to cholesterol lowering . JAMA 1984;;251:365-374.
8 +
Illingworth DR, Sexton GJ:  Hypercholesterolemic effects of mevinolin in patients with heterozygous familial hypercholesterolemia . J Clin Invest 1984;;74:1972-1978.
9 +
Hoeg JM, Maher MB, Zech LA, et al:  Effectiveness of mevinolin on plasma lipoprotein concentration in type II hyperlipoproteinemia . Am J Cardiol 1986;;57:933-939.
10 +
Lovastatin Study Group II:  Therapeutic response to lovastatin (mevinolin) in nonfamilial hypercholesterolemia . JAMA 1986;;256:2829-2834.
11 +
Havel RJ, Hunninghake DB, Illingworth DR, et al:  Lovastatin (mevinolin) in the treatment of heterozygous familial hypercholesterolemia: A multicenter study . Ann Intern Med 1987;;107:609-615.
12 +
Fredrickson DS, Levy RI, Lees RS:  Fat transport in lipoproteins: An integrated approach to mechanism and disorders . N Engl J Med 1967;;276:34-44, 93-103,148-156,215-225,273-281.
13 +
Lipid Research Clinics Program: Manual of Laboratory Operations: Lipid and Lipoprotein Analysis , US Dept of Health, Education, and Welfare publication (NIH) 75:628. Bethesda, Md, National Institutes of Health, 1982;.
14 +
Warnick GR, Albers JJ:  A comprehensive evaluation of the heparin manganese precipitation procedure for estimating high-density lipoprotein cholesterol . J Lipid Res 1978;;19:65-73.
15 +
Mendoza SG, Zerpa A, Carrasco H, et al:  Estradiol, testosterone, apolipoproteins, lipoprotein cholesterol, and lipolytic enzymes in men with premature myocardial infarction and angiographically assessed coronary occlusion . Artery 1983;;12:1-23.
16 +
Stein EA, Dipersio L, Pesce AJ, et al:  Enzymelinked immunoabsorbent assay of apolipoprotein All in plasma, with use of a monoclonal antibody . Clin Chem 1986;;32:967-971.
17 +
Young SG, Smith RS, Hogle DM, et al:  Two new monoclonal antibody-based enzyme-linked assays of apolipoprotein B . Clin Chem 1986;;32:1484-1490.
18 +
Yanagawa T, Kasagi F, Yoshimura T:  A method for estimating incidence rates of onchocerciasis from skin-snip biopsies with consideration of false negatives . Biometrics 1984;;40:301-311.
19 +
Puri ML:  Combining independent one-sample tests of significance . Ann Inst Stat Math 1967;;19:285-300.
20 +
Castelli W, Abbott R, McNamara P:  Summary estimates of cholesterol used to predict coronary heart disease . Circulation 1983;;67:730-734.
21 +
Grundy SM, Ahrens EH Jr, Salen GT:  Interruption of the enterohepatic circulation of bile acids in man: Comparative effects of cholestyramine and ideal exclusion of cholesterol metabolism . J Lab Clin Med 1971;;78:94-121.
22 +
Back P, Hamprecht B, Lynen F:  Regulation of cholesterol biosynthesis in rat liver: Diurnal changes in activity and influence of bile acids . Arch Biochem Biophys 1969;;133:11-21.
23 +
Beil U, Crouse JR, Einarsson K, et al:  Effects on interruption of the enterohepatic circulation of bile acids on the transport of very low-density lipoprotein triglycerides . Metabolism 1982;;31:438-444.
24 +
Witztum JL, Schonfeld G, Wiedman SW, et al:  Bile sequestrant therapy alters the composition of low-density and high-density lipoproteins . Metabolism 1979;;28:221-229.
25 +
Shepherd J, Packard CJ, Bicker S, et al:  Cholestyramine promotes receptor-mediated low-density lipoprotein catabolism . N Engl J Med 1980;; 302:1219-1222.
26 +
Durrington P, Bolton C, Hartog M:  Serum and lipoprotein apolipoprotein B levels in normal subjects and patients with hyperlipoproteinaemia . Clin Chem Acta 1978;;82:151-160.
27 +
Young SG, Witztum JL, Casal DC, et al:  Conservation of the low-density lipoprotein receptorbinding domain of apolipoprotein B . Arteriosclerosis 1986;;6:178-188.
28 +
Bilheimer DW, Grundy SM, Brown MS, et al:  Mevinolin and colestipol stimulate receptor-mediated clearance of low-density lipoprotein from plasma in familial hypercholesterolemia heterozygotes . Proc Natl Acad Sci USA 1983;;80:4124-4128.
29 +
Ma PT, Gil G, Sudhof TC, et al:  Mevinolin, an inhibitor of cholesterol synthesis, induces mRNA for low-density lipoprotein receptor in livers of hamsters and rabbits . Proc Natl Acad Sci USA 1986;;83:8370-8374.
30 +
Grundy SM, Vega GL:  Influence of mevinolin on metabolism of low-density lipoproteins in primary moderate hypercholesterolemia . J Lipid Res 1985;;26:1464-1475.
31 +
Tobert JA:  New developments in lipid-lowering therapy: The role of inhibitors of HMG-CoA reductase . Circulation 1987;;76:534-538.
32 +
Norman DJ, Illingworth DR, Munson J, et al:  Myolysis and acute renal failure in a heart-transplant patient receiving lovastatin . N Engl J Med 1988;;318:46-47.
33 +
East C, Alvizatos PA, Grundy SM, et al:  Rhabdomyolysis in patients receiving lovastatin after cardiac transplantation . N Engl J Med 1988;;318:4748.
34 +
Tobert JA:  Reply . N Engl J Med 1988;;318:48.
35 +
Hunninghake DB, Miller VT, Goldberg I, et al:  Lovastatin: Follow-up ophthalmologic data . JAMA 1988;;259:354-355.
36 +
Blankenhorn DH, Nessim SA, Johnson RL, et al:  Beneficial effects of combined colestipol-niacin therapy on coronary atherosclerosis and coronary venous bypass grafts . JAMA 1987;;257:3233-3240.
37 +
Canner PL, Berg KG, Wenger NK, et al:  Fifteen years mortality in coronary drug project patients: Long-term benefit with niacin . J Am Coll Cardiol 1986;;8:1245-1255.
38 +
Frick MH, Elo O, Haapa K, et al:  Helsinki heart study: Primary prevention trial with gemfibrozil in middle-aged men with dyslipidemia . N Engl J Med 1987;;317:1237-1245.
39 +
Tyroler HA:  Review of lipid-lowering clinical trials in relation to observational epidemiological studies . Circulation 1987;;76:515-522.
40 +
Illingworth DR:  Long-term administration of lovastatin in the treatment of hypercholesterolemia . Eur Heart J 1987;;8( (suppl E) ):103-111.

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