Skip to main content
SpringerLink
Log in

Management of Dyslipidaemias

The Role of Simvastatin

  • Drugs in Disease Management
  • Published:
Disease Management and Health Outcomes

Abstract

Dyslipidaemias are major modifiable risk factors for the development of atherosclerosis and its sequelae, namely coronary heart disease (CHD) and peripheral vascular disease. CHD is the leading cause of morbidity and mortality in men and women in Western countries; the costs associated with this disease are substantial and place a large burden on society.

The goal of therapy in patients with dyslipidaemia is to achieve target serum lipid levels (established by treatment guidelines) in an effort to reduce the risk of asymptomatic individuals developing CHD (primary prevention) or to slow or retard the progression of atherosclerosis in patients with established CHD (secondary prevention). A multifactorial approach including lifestyle modifications and, if necessary, pharmacological intervention is recommended.

Simvastatin is a competitive and reversible inhibitor of the enzyme 3-hydroxy-3-methylglutaryl-coenzyme-A (HMG-CoA) reductase. It causes marked reductions in serum low density lipoprotein cholesterol (LDL-C) levels and reductions in serum triglyceride levels in patients with hypertriglyceridaemia. Simvastatin also increases serum high density lipoprotein cholesterol (HDL-C) levels and is the first HMG-CoA reductase inhibitor indicated for this use.

The Scandinavian Simvastatin Survival Study (4S) established that simvastatin 20 to 40 mg/day reduces total mortality (by 30% at 5 years compared with placebo) in patients with CHD, mostly because of a reduction in cardiovascular mortality (42% reduction at 5 years). This reduction in mortality was maintained for at least 8 years in simvastatin-treated patients in 4S. As secondary prevention simvastatin is cost effective in men, women and diabetic patients with CHD as shown by data from 4S. Available evidence also indicates that simvastatin slows the progression of coronary atherosclerosis. In patients with diabetes and CHD, 5-years’ treatment with simvastatin during 4S reduced the risk of coronary death and nonfatal myocardial infarction by 55% compared with a 32% reduction in nondiabetic patients with CHD. In high risk patients with CHD, other cardiovascular risk factors and dyslipidaemia, simvastatin 40 to 80 mg/day effectively reduced serum LDL-C and triglyceride levels and raised HDL-C levels.

The most common adverse events associated with simvastatin in clinical trials of 5 to 10 years’ duration were gastrointestinal upset and headache. These events were similar in incidence to that with placebo and did not necessitate a discontinuation of therapy. Asymptomatic elevations in hepatic transaminase levels and, rarely, myopathy have been described during simvastatin treatment.

Conclusions: The efficacy and tolerability of simvastatin at doses of up 80 mg/day are well established. Together with favourable effects on serum lipoprotein levels compared with related compounds and, more importantly, beneficial long term effects on morbidity and mortality in patients with CHD, simvastatin is firmly established as a first-line agent when cholesterol-altering pharmacotherapy is indicated for treatment of dyslipidaemia.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Table I
Table II
Table III
Table IV
Fig. 1
Fig. 2
Table V
Fig. 3
Table VI
Table VII
Table VIII

Similar content being viewed by others

References

  1. Plosker GL, McTavish D. Simvastatin: a reappraisal of its pharmacology and therapeutic efficacy in hypercholesterolaemia. Drugs 1995 Aug; 50: 334–63

    Article  PubMed  CAS  Google Scholar 

  2. Betteridge DJ, Dodson PM, Durrington PN, et al. Management of hyperlipidaemia: guidelines of the British Hyperlipidaemia Association. Postgrad Med J 1993; 69: 359–69

    Article  PubMed  CAS  Google Scholar 

  3. Ginsberg HN, Goldberg IJ. Disorders of lipoprotein metabolism. In: Fauci AS, Braunwald E, Isselbacher KJ, et al., editors. Harrison’ principles of internal medicine. 14th ed. New York: McGraw-Hill, 1998: 2138–49

    Google Scholar 

  4. Grundy SM, Bilheimer D, Chait A, et al. 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 Jun 16; 269: 3015–23

    Article  Google Scholar 

  5. Stone NJ. Secondary causes of hyperlipidemia. Med Clin North Am 1994 Jan; 78: 117–41

    PubMed  CAS  Google Scholar 

  6. Gaziano JM, Hennekens CH, O’Donnell CJ, et al. Fasting triglycerides, high-density lipoprotein, and risk of myocardial infarction. Circulation 1997; 96: 2520–5

    Article  PubMed  CAS  Google Scholar 

  7. Assmann G, Schulte H, von Eckardstein A. Hypertriglyceridemia and elevated lipoprotein(a) are risk factors for major coronary events in middle-aged men. Am J Cardiol 1996; 77: 1179–84

    Article  PubMed  CAS  Google Scholar 

  8. Cleeman JI, Lenfant C. The National Cholesterol Education Program: progress and prospects. JAMA 1998 Dec 23-30; 280: 2099–104

    Article  PubMed  CAS  Google Scholar 

  9. Rubins HB, Robins SJ, Collins D, et al. Gemfibrozil for the secondary prevention of coronary heart disease in men with low levels of high-density lipoprotein cholesterol. N Engl J Med 1999; 341: 410–8

    Article  PubMed  CAS  Google Scholar 

  10. Wood D, De Backer G, Faergeman O, et al. Prevention of coronary heart disease in clinical practice: recommendations of the Second Joint Task Force of European and other Societies on Coronary Prevention. Eur Heart J 1998 Oct; 19: 1434–503

    Article  Google Scholar 

  11. Gordon DJ, Probstfield RJ, Garrison RJ, et al. High-density lipoprotein cholesterol and cardiovascular disease. Four prospective American studies. Circulation 1989; 79: 8–15

    Article  PubMed  CAS  Google Scholar 

  12. National Cholesterol Education Program. Second report of the expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel II). Circulation 1994; 89(3): 1333–445

    Article  Google Scholar 

  13. American Heart Association. 1999 Heart and Stroke Statistical Update. Dallas: American Heart Association, 1998

  14. Reckless JPD. Cost-effectiveness of hypolipidaemic drugs. Postgrad Med J 1993; 69 Suppl. 1: S30–3

    PubMed  Google Scholar 

  15. Alexander CM, Landsman PB, Boccuzzi SJ, et al. Impaired fasting glucose, lipid levels and prevalence of coronary heart disease: A US population perspective [abstract no. 294]. Diabetes 1998 May; 47 Suppl. 1: A75

    Google Scholar 

  16. Thelle DS. Epidemiology of hypercholesterolemia and European management guidelines. Cardiology 1990; 77 Suppl. 4: 2–7

    Article  PubMed  Google Scholar 

  17. EUROASPIRE Study Group. EUROASPIRE. A European Society of Cardiology survey of secondary prevention of coronary heart disease: principal results. Eur Heart J 1997; 18: 1569–82

    Article  Google Scholar 

  18. Turner RC, Millns H, Neil HAW, et al. Risk factors for coronary artery disease in non-insulin dependent diabetes mellitus: United Kingdom prospective diabetes study (UKPDS: 23). BMJ 1998; 316: 823–8

    Article  PubMed  CAS  Google Scholar 

  19. Stamler J, Vaccaro O, Neaton JD, et al. Diabetes, other risk factors, and 12-yr cardiovascular mortalilty for men screened in the Multiple Risk Factor Intervention Trial. Diabetes Care 1993; 16: 434–44

    Article  PubMed  CAS  Google Scholar 

  20. Grundy SM, Balady GJ, Criqui MH, et al. Primary prevention of coronary heart disease: guidance from Framingham. A statement for healthcare professionals from the AHA Task Force on Risk Reduction. Circulation 1998; 97: 1876–87

    Article  PubMed  CAS  Google Scholar 

  21. MRC/BHF Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol-lowering therapy and of antioxidant vitamin supplementation in a wide range of patients at increased risk of coronary heart disease death: early safety and efficacy experience. Eur Heart J 1999; 20: 725–41

    Article  Google Scholar 

  22. Pedersen TR, Kjekahus J, Berg K. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet 1994 Nov 19; 344: 1383–9

    Article  Google Scholar 

  23. Sacks FM, Pfeffer MA, Moye LA, et al. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. N Engl J Med 1996; 335(14): 1001–9

    Article  PubMed  CAS  Google Scholar 

  24. Pyörälä K, Pedersen TR, Kjekshus J, et al. Cholesterol lowering with simvastatin improves prognosis of diabetic patients with coronary heart disease: a subgroup analysis of the Scandinavian Simvastatin Survival Study (4S). Diabetes Care 1997 Apr; 20: 614–20

    Article  PubMed  Google Scholar 

  25. Haffner SM. Management of dyslipidemia in adults with diabetes. Diabetes Care 1998 Jan; 21: 160–78

    Article  PubMed  CAS  Google Scholar 

  26. Shepherd J, Cobbe S, Ford I, et al. Prevention of coronary heart diseasse with pravastatin in men with hypercholesterolemia. N Engl J Med 1995; 333: 1301–7

    Article  PubMed  CAS  Google Scholar 

  27. Downs J, Clearfield M, Weis S, et al. Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels. Results of AFCAPS/TexCAPS. JAMA 1998; 279(20): 1615–22

    Article  PubMed  CAS  Google Scholar 

  28. Pedersen TR, Kjekshus J, Berg K, et al. Cholesterol lowering and the use of healthcare resources: results of the Scandinavian Simvastatin Survival Study. Circulation 1996 May 15; 95: 1796–802

    Article  Google Scholar 

  29. Campeau L, Knatterud GL, Domanski M, et al. The effect of aggressive lowering of low-density lipoprotein cholesterol levels and low-dose anticoagulation on obstructive changes in saphenous-vein coronary-artery bypass grafts. N Engl J Med 1997; 336: 153–62

    Article  CAS  Google Scholar 

  30. American Diabetes Association. Management of dyslipidemia in adults with diabetes. Diabetes Care 1999 Jan; 22 Suppl. 1: S56–9

    Google Scholar 

  31. Avins AL, Browner WS. Improving the prediction of coronary heart disease to aid in the management of high cholesterol levels: what a difference a decade makes. JAMA 1998 Feb 11; 279: 445–9

    Article  PubMed  CAS  Google Scholar 

  32. Grundy SM, Balady GJ, Criqui MH, et al. When to start cholesterol-lowering therapy in patients with coronary heart disease: a statement for healthcare professionals from the American Heart Association Task Force on Risk Reduction. Circulation 1997; 95: 1683–5

    Article  PubMed  CAS  Google Scholar 

  33. Carr A, Samaras K, Chisholm DJ, et al. Pathogenesis of HIV-1-protease inhibitor-associated peripheral lipodystrophy, hyperlipidaemia, and insulin resistance. Lancet 1998 Jun 20; 351: 1881–3

    Article  PubMed  CAS  Google Scholar 

  34. Willett WC, Dietz WH, Colditz GA. Guidelines for healthy weight. N Engl J Med 1999; 341(6): 427–34

    Article  PubMed  CAS  Google Scholar 

  35. Leon AS, Connett J, Jacobs Jr DR, et al. Leisure-time physical activity levels and risk of coronary heart disease and death. The Multiple Risk Factor Intervention Trial. JAMA 1987; 258: 2388–95

    Article  PubMed  CAS  Google Scholar 

  36. Paffenbarger Jr RS, Hyde RT, Wing AL, et al. The association of changes in physical-activity level and other lifestyle characteristics with mortality among men. N Engl J Med 1993; 328: 538–45

    Article  PubMed  Google Scholar 

  37. Pate RR, Pratt M, Blair SN, et al. Physical activity and public health: a recommendation from the Centers for Disease Control and Prevention and the American College of Sports Medicine. JAMA 1995; 273: 402–7

    Article  PubMed  CAS  Google Scholar 

  38. American Diabetes Association. Diabetes mellitus and exercise. Diabetes Care 1997; 20 Suppl. 1: S51

    Google Scholar 

  39. Aquilani R, Tramarin R, Pedretti RF, et al. Despite good compliance, very low fat diet alone does not achieve recommended cholesterol goals in outpatients with coronary heart disease. Eur Heart J 1999; 20(14): 1020–9

    Article  PubMed  CAS  Google Scholar 

  40. Pedersen TR, Jahnsen KE, Vatn S, et al. Lipid intervention strategies in acute coronary syndromes: a randomised trial with simvastatin [abstract]. Atherosclerosis 1999 May; 144 Suppl. 1: 198

    Article  Google Scholar 

  41. Durrington P. Statins and fibrates in the management of diabetic dyslipidaemia [editorial; comment]. Diabet Med 1997 Jul; 14: 513–6

    Article  PubMed  CAS  Google Scholar 

  42. Knopp RH. Drug treatment of lipid disorders. N Engl J Med 1999; 341(7): 498–511

    Article  PubMed  CAS  Google Scholar 

  43. Adkins JC, Faulds D. Micronised fenofibrate: a review of its pharmacodynamic properties and clinical efficacy in the management of dyslipidaemia. Drugs 1997 Oct; 54: 615–33

    Article  PubMed  CAS  Google Scholar 

  44. Brown BG, Albers JJ, Fisher 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; 323: 1289–98

    Article  PubMed  CAS  Google Scholar 

  45. Frick MH, Elo O, Haapa K, et al. Helsinki Heart Study: primary-prevention trial with gemfibrozil in middle-aged men with dyslipidemia. Safety of treatment, changes in risk factors, and incidence of coronary heart disease. N Engl J Med 1987; 317: 1237–45

    Article  PubMed  CAS  Google Scholar 

  46. The Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study Group. Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. N Engl J Med 1998; 339: 1349–57

    Article  Google Scholar 

  47. Lipid Research Clinics Program. The Lipid Research Clinics Coronary Primary Prevention Trial results. Reduction in incidence of coronary heart disease. JAMA 1984; 251: 351–64

    Article  Google Scholar 

  48. Coronary Drug Project Research Group. Clofibrate and niacin in coronary heart disease. JAMA 1975; 231: 360–81

    Article  Google Scholar 

  49. 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: 1245–55

    Article  PubMed  CAS  Google Scholar 

  50. Stein EA, Plotkin D, Hunninghake DB, et al. Lipid altering efficacy of simvastatin in patients with hypertriglyceridemia. Atherosclerosis 1999; 144 Suppl. 1: 30

    Article  Google Scholar 

  51. Isaacsohn J, Hunninghake D, Schrott HA, et al. The efficacy of simvastatin in patients with hypertriglyceridemia. Atherosclerosis 1999; 144 Suppl. 1: 39

    Article  Google Scholar 

  52. Branchi A, Fiorenza AM, Rovellini A, et al. Lowering effects of four different statins on serum triglyceride level. Eur J Clin Pharmacol 1999; 55: 499–502

    Article  PubMed  CAS  Google Scholar 

  53. Stein EA. Extending therapy options in treating lipid disorders: a clinical review of cerivastatin, a novel HMG-CoAreductase inhibitor. Drugs 1998; 56 Suppl. 1: 25–31

    Article  PubMed  CAS  Google Scholar 

  54. Brown AS, Bakker-Arkema RG, Yellen L, et al. Treating patients with documented atherosclerosis to National Cholesterol Education Program-recommended low-density-lipoprotein cholesterol goals with atorvastatin, fluvastatin, lovastatin and simvastatin. J Am Coll Cardiol 1998 Sep; 32: 665–72

    Article  PubMed  CAS  Google Scholar 

  55. Dart A, Jerums G, Nicholson G, et al. A multicenter, doubleblind, one-year study comparing safety and efficacy of atorvastatin versus simvastatin in patients with hyper-cholesterolemia. Am J Cardiol 1997 Jul 1; 80: 39–44

    Article  PubMed  CAS  Google Scholar 

  56. Miettinen TA, Pyörälä K, Olsson AG, et al. Cholesterol-lowering therapy in women and elderly patients with myocardial infarction or angina pectoris: findings from the Scandinavian Simvastatin Survival Study (4S). Circulation 1997 Dec 16; 96: 4211–8

    Article  PubMed  CAS  Google Scholar 

  57. Gotto Jr AM. Cholesterol management in theory and practice. Circulation 1997; 96(12): 4424–30

    Article  PubMed  Google Scholar 

  58. Mosca L, Grundy SM, Judelson D, et al. AHA/ACC Scientific Statement: Consensus Panel Statement. Guide to preventive cardiology for women. Circulation 1999; 99: 2480–4

    Article  PubMed  CAS  Google Scholar 

  59. Brown BG, Zhao X-Q, Sacco DE, et al. Lipid lowering and plaque regression. New insights into prevention of plaque disruption and clinical events in coronary disease. Circulation 1993 Jun; 87: 1781–91

    Article  PubMed  CAS  Google Scholar 

  60. Treasure CB, Klein JL, Weintraub WS, et al. Beneficial effects of cholesterol-lowering therapy on the coronary endothelium in patients with coronary artery disease. N Engl J Med 1995; 332: 481–7

    Article  PubMed  CAS  Google Scholar 

  61. Rosenson RS, Tangney CC. Antiatherothrombotic properties of statins: implications for cardiovascular event reduction. JAMA 1998 May 27; 279: 1643–50

    Article  PubMed  CAS  Google Scholar 

  62. Strandberg TE, Vanhanen H, Tikkanen MJ. Effect of statins on C-reactive protein in patients with coronary artery disease. Lancet 1999 Jan 9; 353: 118–9

    Article  PubMed  CAS  Google Scholar 

  63. Ridker PM, Rifai N, Pfeffer MA, et al. Inflammation, pravastatin, and the risk of coronary events after myocardial infarction in patients with average cholesterol levels. Circulation 1998; 98: 839–44

    Article  PubMed  CAS  Google Scholar 

  64. Bruckert E, DeGennes JL, Malbecq W, et al. Comparison of the efficacy of simvastatin and standard fibrate therapy in the treatment of primary hypercholesterolemia and combined hyperlipidemia. Clin Cardiol 1995 Nov; 18: 621–9

    Article  PubMed  CAS  Google Scholar 

  65. de Graaf J, Hendriks JCM, Demacker PNM, et al. Identification of multiple dense LDL subfractions with enhanced susceptibility to in vitro oxidation among hypertriglyceridemic subjects. Normalization after clofibrate treatment. Arterioscler Thromb 1993; 13: 712–9

    Article  PubMed  Google Scholar 

  66. Farmer JA, Gotto Jr AM. Choosing the right lipid-regulating agent: a guide to selection. Drugs 1996 Nov; 52: 649–61

    Article  PubMed  CAS  Google Scholar 

  67. Knopp RH, Alagona P, Davidson M, et al. Equivalent efficacy of a time-release form of niacin (Niaspan) given once-a-night versus plain niacin in the management of hyperlipidemia. Metabolism 1998; 47: 1097–104

    Article  PubMed  CAS  Google Scholar 

  68. Carlson LA, Hamsten A, Asplund A. Pronounced lowering of serum levels of lipoprotein Lp(a) in hyperlipidaemic subjects with nicotinic acid. J Intern Med 1989; 226: 271–6

    Article  PubMed  CAS  Google Scholar 

  69. Superko HR, Greenland P, Manchester RA, et al. Effectiveness of low-dose colestipol therapy in patients with moderate hypercholesterolemia. Am J Cardiol 1992; 70: 135–40

    Article  PubMed  CAS  Google Scholar 

  70. Darling GM, Johns JA, McCloud PI, et al. Estrogen and progestin compared with simvastatin for hypercholesterolemia in postmenopausal women. N Engl J Med 1997 Aug 28; 337: 595–601

    Article  PubMed  CAS  Google Scholar 

  71. McKinney KA, Thompson W. A practical guide to prescribing hormone replacement therapy. Drugs 1998; 56(1): 49–57

    Article  PubMed  CAS  Google Scholar 

  72. Hulley S, Grady D, Bush T, et al. Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. JAMA 1998; 280: 605–13

    Article  PubMed  CAS  Google Scholar 

  73. Shepherd J. Fibrates and statins in the treatment of hyperlipidaemia: an appraisal of their efficacy and safety. Eur Heart J 1995 Jan; 16: 5–13

    Article  PubMed  CAS  Google Scholar 

  74. Pedersen TR, Berg K, Cook TJ, et al. Safety and tolerability of cholesterol lowering with simvastatin during 5 years in the Scandinavian Simvastatin Survival Study. Arch Intern Med 1996 Oct 14; 156: 2085–92

    Article  PubMed  CAS  Google Scholar 

  75. Guyton JR, Capuzzi DM. Treatment of hyperlipidemia with combined niacin-statin regimens. Am J Cardiol 1998 Dec 17; 82 Suppl. 12A: 82U–4U

    Article  PubMed  CAS  Google Scholar 

  76. Ellen RLB, McPherson R. Long-term efficacy and safety of fenofibrate and a statin in the treatment of combined hyperlipidemia. Am J Cardiol 1998 Feb 26; 81: 60–5

    Article  Google Scholar 

  77. Feher MD, Foxton J, Banks D, et al. Long-term safety of statinfibrate combination treatment in the management of hyper cholesterolaemia in patients with coronary artery disease. Br Heart J 1995 Jul; 74: 14–7

    Article  PubMed  CAS  Google Scholar 

  78. Slater EE, MacDonald JS. Mechanism of action and biological profile of HMG CoA reductase inhibitors: a new therapeutic alternative. Drugs 1988; 36 Suppl. 3: 72–82

    Article  PubMed  CAS  Google Scholar 

  79. Grundy SM. HMG-CoA reductase inhibitors for treatment of hypercholesterolemia. N Engl J Med 1988 Jul 7; 319: 24–33

    Article  PubMed  CAS  Google Scholar 

  80. Mölgaard J, Wärjerstam-Elf S, Olsson AG. Efficacy and safety of simvastatin for high-risk hypercholesterolemia. Am J Cardiol 1999 Apr 1; 83: 1043–8

    Article  PubMed  Google Scholar 

  81. Stein EA, Davidson MH, Dobs AS, et al. Efficacy and safety of simvastatin 80 mg/day in hypercholesterolemic patients. Am J Cardiol 1998 Aug 1; 82: 311–6

    Article  PubMed  CAS  Google Scholar 

  82. Ose L, Kastelein JJP, Scott R, et al. Efficacy and six-month safety of simvastatin 80 mg/day: results from the Worldwide Simvastatin Expanded Dose Program (WSEDP). Nutr Metabol Cardiovasc Dis 1998 Jun; 8: 135–43

    CAS  Google Scholar 

  83. Pedersen TR, Wilhelmsen L, Faergeman O, et al. Extended follow-up of patients in the Scandinavian Simvastatin Survival Study (4S) shows increased survival benefit of simvastatin therapy [abstract]. Circulation 1998 Oct 27; 98 Suppl.: I–451

    Google Scholar 

  84. Davidson MH, Stein EA, Dujovne CA, et al. The efficacy and six-week tolerability of simvastatin 80 and 160 mg/day. Am J Cardiol 1997 Jan 1; 79: 38–42

    Article  PubMed  CAS  Google Scholar 

  85. Lennernäs H, Fager G. Pharmacodynamics and pharmacokinetics of the HMG-CoA reductase inhibitors: similarities and differences. Clin Pharmacokinet 1997 May; 32: 403–25

    Article  PubMed  Google Scholar 

  86. Crouse III JR, Frolich J, Ose L, et al. Effects of high doses of simvastatin and atorvastatin on high-density lipoprotein cholesterol and apolipoprotein A-1. Am J Cardiol 1999 May 15: 1476–7

    Article  Google Scholar 

  87. Jones P, Kafonek S, Laurora I, et al. Comparative dose efficacy study of atorvastatin versus simvastatin, pravastatin, lovastatin, and fluvastatin in patients with hypercholesterolemia (The CURVES Study). Am J Cardiol 1998 Mar 1; 81: 582–7

    Article  PubMed  CAS  Google Scholar 

  88. Haria M, McTavish D. Pravastatin: a reappraisal of its pharmacological properties and clinical effectiveness in the management of coronary heart disease. Drugs 1997 Feb; 53: 299–336

    Article  PubMed  CAS  Google Scholar 

  89. Bristol-Meyers Squibb Company. Pravachol (pravastatin sodium) Product information. Princeton (NJ), 1998

  90. Plosker GL, Wagstaff AJ. Fluvastatin: a review of its pharmacology and use in the management of hypercholesterolaemia. Drugs 1996 Mar; 51: 433–59

    Article  PubMed  CAS  Google Scholar 

  91. McClellan KJ, Wiseman LR, McTavish D. Cerivastatin. Drugs 1998 Mar; 55: 415–20

    Article  PubMed  CAS  Google Scholar 

  92. Bischoff H, Heller AH. Preclinical and clinical pharmacology of cerivastatin. Am J Cardiol 1998; 82: 18J–25J

    Article  PubMed  CAS  Google Scholar 

  93. Boberg M, Angerbauer R, Fey P, et al. Metabolism of cerivastatin by human liver microsomes in vitro: characterization of primary metabolic pathways and of cytochrome P450 isoenzymes involved. Drug Metab Dispos 1997; 25(3): 321–31

    PubMed  CAS  Google Scholar 

  94. Bayer Corporation. Baycol (cerivastatin sodium tablets). West Haven (CT), 1999

  95. Lea AP, McTavish D. Atorvastatin: a review of its pharmacology and therapeutic potential in the management of hyperlipidaemias. Drugs 1997 May; 53: 828–47

    Article  PubMed  CAS  Google Scholar 

  96. Pitt B, Waters D, Brown WV, et al. Aggressive lipid-lowering therapy compared with angioplasty in stable coronary artery disease. Atorvastatin versus Revascularization Treatment Investigators. N Engl J Med 1999; 341: 70–6

    Article  PubMed  CAS  Google Scholar 

  97. Parke-Davis. Lipitor (atorvastatin calcium) Product information. Morris Plains (NJ), 1999

  98. Merck. Zocor (simvastatin) Product information. West Point (PA), 1999

  99. Hunninghake DB, Plotkin D, Stepanavage M, et al. Large and dose dependent effects of simvastatin 40 and 80 mg/day in combined hyperlipidemia [abstract]. Atherosclerosis 1999; 144 Suppl. 1: 191

    Google Scholar 

  100. Raal FJ, Pilcher GJ, Illingworth DR, et al. Expanded-dose simvastatin is effective in homozygous familial hypercholesterolaemia. Atherosclerosis 1997 Dec; 135: 249–56

    Article  PubMed  CAS  Google Scholar 

  101. Sigurdsson G, Haraldsdottir SO, Melberg TH, et al. Simvastatin compared to fluvastatin in the reduction of serum lipids and apolipoproteins in patients with ischaemic heart disease and moderate hypercholesterolaemia. Acta Cardiol 1998; 53(1): 7–14

    PubMed  CAS  Google Scholar 

  102. Simvastatin Pravastatin Study Group. Comparison of the efficacy, safety and tolerability of simvastatin and pravastatin for hypercholesterolemia. Am J Cardiol 1993 Jun 15; 71: 1408–14

    Article  Google Scholar 

  103. Ose L, Scott R, Simvastatin-Fluvastatin Study Group. Doubleblind comparison of the efficacy and tolerability of simvastatin and fluvastatin in patients with primary hypercholesterolaemia. Clin Drug Invest 1995 Sep; 10: 127–38

    Article  CAS  Google Scholar 

  104. Farmer JA, Washington LC, Jones PH. Comparative effects of simvastatin and lovastatin in patients with hypercholesterolemia. Clin Ther 1992 Sep-Oct; 14: 708–17

    PubMed  CAS  Google Scholar 

  105. Betteridge DJ. International multicentre comparison of cerivastatin with placebo and simvastatin for the treatment of patients with primary hypercholesterolaemia. Int J Clin Pract 1999; 53(4): 243–50

    PubMed  CAS  Google Scholar 

  106. Leiter LA, Hanna K, Canadian Cerivastatin Study Group. Efficacy and safety of cerivastatin in primary hypercholesterolemia: A long term comparative titration study with simvastatin. Can J Cardiol 1999; 15(5): 545–55

    PubMed  CAS  Google Scholar 

  107. Best J, Dart A, Hamilton I, et al. A one-year study comparing atorvastatin and simvastatin in patients with hypercholesterolemia. Presented at the 66th Congress of the European Atherosclerosis Society; Florence, Italy; 13 Jul 1996

  108. Recto II CS, Acosta S, Dobs A. Comparison of the efficacy and tolerability of simvastatin and atorvastatin in the treatment of hypercholesterolemia. Clin Cardiol. In press

  109. Merck & Co Inc. Zocor(R) (simvastatin) gains exclusive indication to raise good (HDL) cholesterol in people with high bad (LDL) cholesterol. Media Release: [2 pages], 9 Aug 1999. Available from: URL: http://www.merck.com

  110. Wierzbicki AS, Lumb PJ, Chik G, et al. Comparison of therapy with simvastatin 80mg and atorvastatin 80mg in patients with familial hypercholesterolaemia. Int J Clin Pract 1999; 53: 609–11

    PubMed  CAS  Google Scholar 

  111. Farrer M, Winocour PH, Evans K, et al. Simvastatin in noninsulin-dependent diabetes mellitus: effect on serum lipids, lipoproteins and haemostatic measures. Diabetes Res Clin Pract 1994 Mar; 23: 111–9

    Article  PubMed  CAS  Google Scholar 

  112. Hwu CM, Kwok CF, Chen HS, et al. Lack of effect of simvastatin on insulin sensitivity in Type 2 diabetic patients with hypercholesterolaemia: results from a double-blind, randomized, placebo-controlled crossover study. Diabetic Med 1999; 16: 749–54

    Article  PubMed  CAS  Google Scholar 

  113. Tikkanen MJ, Laakso M, Ilmonen M, et al. Treatment of hypercholesterolemia and combined hyperlipidemia with simvastatin and gemfibrozil in patients with NIDDM: a multicenter comparison study. Diabetes Care 1998 Apr; 21: 477–81

    Article  PubMed  CAS  Google Scholar 

  114. Jeck T, Riesen WF, Keller U. Comparison of bezafibrate and simvastatin in the treatment of dyslipidaemia in patients with NIDDM. Diabetic Med 1997 Jul; 14: 564–70

    Article  PubMed  CAS  Google Scholar 

  115. Ryan TJ, Anderson JL, Antman EM, et al. ACC/AHA Guidelines for the Management of Patients with Acute Myocardial Infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Comittee on Management of Acute Myocardial Infarction). J Am Coll Cardiol 1996; 28: 1328–428

    Article  PubMed  CAS  Google Scholar 

  116. Khong TK, Missouris CG, Murda’h M. The use of HMG Co-A reductase inhibitors following acute myocardial infarction in hospital practice. Postgrad Med J 1998 Oct; 74: 600–1

    Article  PubMed  CAS  Google Scholar 

  117. Pedersen TR, Kjekshus J, Berg K. Baseline serum cholesterol and treatment effect in the Scandinavian Simvastatin Survival Study (4S). Lancet 1995 May 20; 345: 1274–5

    Google Scholar 

  118. Hebert PR, Gaziano JM, Chan KS, et al. Cholesterol lowering with statin drugs, risk of stroke, and total mortality: an overview of randomized trials. JAMA 1997 Jul 23-30; 278: 313–21

    Article  PubMed  CAS  Google Scholar 

  119. Gorelick PB, Sacco RL, Smith DB, et al. Prevention of a first stroke: a review of guidelines and a multidisciplinary consensus statement from the National Stroke Association. JAMA 1999 Mar 24-31; 281: 1112–20

    Article  PubMed  CAS  Google Scholar 

  120. Oliver MF, de Feyter PJ, Lubsen J, et al. Effect of simvastatin on coronary atheroma: the Multicentre Anti-Atheroma Study (MAAS). Lancet 1994 Sep 3; 344: 633–8

    Article  Google Scholar 

  121. Bestehorn H-P, Rensing UFE, Roskamm H, et al. The effect of simvastatin on progression of coronary artery disease: the Multicenter Coronary Intervention Study (CIS). Eur Heart J 1997 Feb; 18: 226–34

    Article  PubMed  CAS  Google Scholar 

  122. Haffner SM, Alexander CM, Cook TJ, et al. Reduced coronary events in simvastatin-treated patients with coronary heart disease and diabetes or impaired fasting glucose levels. Subgroup analyses in the Scandanavian Simvastatin Survival Study. Arch Intern Med 1999; 159: 2661–7

    Article  PubMed  CAS  Google Scholar 

  123. Gruer PJK, Vega JM, Mercuri MF, et al. Concomitant use of cytochrome P450 3A4 inhibitors and simvastatin. Am J Cardiol 1999; 84: 811–5

    Article  PubMed  CAS  Google Scholar 

  124. Davidson MH, Stein EA, Hunninghake D, et al. The efficacy and safety of simvastatin 80mg; pooled results from world-wide clinical studies. Atherosclerosis 1999; 144 Suppl. 1: 30

    Article  Google Scholar 

  125. Kastelein JP, Ose L, Stein EA, et al. Simvastatin 80 mg/d is effective and well tolerated: results from long term studies in more than 1000 patients [abstract]. 13th International Symposium on Drugs Affecting Lipid Metabolism; Florence, Italy 1998 May 30: 79

  126. Campana C, Iacona I, Regazzi MB, et al. Efficacy and pharmacokinetics of simvastatin in heart transplant recipients. Ann Pharmacother 1995 Mar; 29: 235–9

    PubMed  CAS  Google Scholar 

  127. Vanhaecke J, Van Cleemput J, Van Lierde J, et al. Safety and efficacy of low dose simvastatin in cardiac transplant recipients treated with cyclosporine. Transplantation 1994 Jul 15; 58: 42–5

    PubMed  CAS  Google Scholar 

  128. Arnadottir M, Eriksson L-O, Germershausen JI, et al. Low-dose simvastatin is a well-tolerated and efficacious cholesterollowering agent in ciclosporin-treated kidney transplant recipients: double-blind, randomized, placebo-controlled study in 40 patients. Nephron 1994 Sep; 68: 57-62

    Google Scholar 

  129. Capone D, Stanziale P, Gentile A, et al. Effects of simvastatin and pravastatin on hyperlipidemia and cyclosporin blood levels in renal transplant recipients. Am J Nephrol 1999; 19(3): 411–5

    Article  PubMed  CAS  Google Scholar 

  130. Mölgaard J, Lundh BL, von Schenck H, et al. Long-term efficacy and safety of simvastatin alone and in combination therapy in treatment of hypercholesterolaemia. Atherosclerosis 1991 Dec; 91 Suppl.: S21–8

    Article  PubMed  Google Scholar 

  131. Bilheimer DW. Long-term clinical tolerance of lovastatin and simvastatin. Cardiology 1990; 77 Suppl. 4: 58–65

    Article  PubMed  Google Scholar 

  132. Boccuzzi SJ, Bocanegra TS, Walker JF, et al. Long-term safety and efficacy profile of simvastatin. Am J Cardiol 1991; 68: 1127–31

    Article  PubMed  CAS  Google Scholar 

  133. Leino M, Rouhiainen P, Tuovinen E, et al. Lens opacity: five year follow-up of patients with hypercholesterolemia receiving simvastatin treatment. J Toxicol Cutaneous Ocul Toxicol 1993; 12(4): 285–92

    Article  Google Scholar 

  134. Johannesson M, Jönsson B, Kjekshus J, et al. Cost effectiveness of simvastatin treatment to lower cholesterol levels in patients with coronary heart disease. N Engl J Med 1997 Jan 30; 336: 332–6

    Article  PubMed  CAS  Google Scholar 

  135. Jönsson B, Johannesson M, Kjekshus J. Cost-effectiveness of cholesterol lowering: results from the Scandinavian Simva-statin Survival Study (4S). Eur Heart J 1996 Jul; 17: 1001–7

    Article  PubMed  Google Scholar 

  136. Grover SA, Coupal L, Paquet S. Cost-effectiveness of 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors in the secondary prevention of cardiovascular disease: forecasting the incremental benefits of preventing coronary and cerebrovascular events. Arch Intern Med 1999 Mar 22; 159: 593–600

    Article  PubMed  CAS  Google Scholar 

  137. Goldman L, Garber AM, Grover SA, et al. Task force 6. Cost effectiveness of assessment and management of risk factors. J Am Coll Cardiol 1996 Apr; 27: 1020–30

    Article  PubMed  CAS  Google Scholar 

  138. Herman WH, Alexander CM, Cook JR, et al. Effect of simvastatin treatment on cardiovascular resource utilization in impaired fasting glucose and diabetes. Diabetes Care 1999; 22: 1771–8

    Article  PubMed  CAS  Google Scholar 

  139. Jönsson B, Cook JR, Pedersen TR. The cost-effectiveness of lipid lowering in patients with diabetes: results from the 4S trial. Diabetologia 1999; 42: 1293–301

    Article  PubMed  Google Scholar 

  140. Goa KL, Barradell LB, McTavish D. Simvastatin: a reappraisal of its cost effectiveness in dyslipidaemia and coronary heart disease. Pharmacoeconomics 1997 Jan; 11: 89–110

    Article  PubMed  CAS  Google Scholar 

  141. Ose L, Davidson MH, Stein EA, et al. Lipid-altering efficacy and safety of simvastatin 80 mg/day: long-term experience in a large group of patients with hypercholesterolemia. Clin Cardiol 2000; 23: 39–46

    Article  PubMed  CAS  Google Scholar 

  142. Merck Sharp & Dohme Ltd. Study of the effectiveness of additional reductions in cholesterol and homocysteine (SEARCH). Merck Sharp & Dohme Ltd (Hertfordshire), 1998 (Data on file)

  143. Scrip. Merck’ “A to Z” unstable angina trial. Scrip 1999 Sep 10 (2471): 19

  144. Merck & Co. 4S & Beyond. Simvastatin targets atherosclerosis and cardiovascular disease: exciting new studies for the next millenium. Merck & Co., Inc., 1999 (Data on file)

  145. Rindone JP, Arriola G. Conversion from fluvastatin to simvastatin therapy at a dose ratio of 8 to 1: effect on serum lipid levels and cost. Clin Ther 1998 Mar-Apr; 20: 340–6

    Article  PubMed  CAS  Google Scholar 

  146. Giles PD, Cunnington AR, Payne M, et al. Cholesterol reduction for the secondary prevention of coronary heart disease: a successful multi-disciplinary approach to implementing evidence-based treatment in a district general hospital. J Clin Effect 1998 Dec; 3: 156–60

    Google Scholar 

  147. Cattin L, DaCol PG, Bordin P, et al. Efficacy and safety of simvastatin in current clinical practice: the Italian Family Physician Simvastatin Study. Curr Ther Res Clin Exp 1996 Jun; 57: 418–29

    Article  CAS  Google Scholar 

  148. Petitta A, Ward RE, Anandan JV, et al. The cost-effectiveness impact of a preferred agent HMG-CoA reductase inhibitor policy in a managed care population. J Manage Care Pharm 1997 Sep-Oct; 3: 548–53

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Adis International Limited, 41 Centorian Drive, Private Bag 65901, Mairangi Bay, Auckland 10, New Zealand

    Karen M. Hvizdos & Karen L. Goa

Authors
  1. Karen M. Hvizdos
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Karen L. Goa
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Karen M. Hvizdos.

Additional information

Various sections of the manuscript reviewed by: B.G. Brown, University of Washington School of Medicine, Seattle, Washington, USA; J.R. Crouse, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA; J.A. Farmer, Baylor College of Medicine, Houston, Texas, USA; M.L. Kashyap, University of California, Irvine, Cholesterol Research Center, Long Beach, California, USA; N. Lewis, Lewis Consulting Group, Inc., Wilmington, Delaware, USA; A.G. Olsson, Clinical Research Center, University Hospital, Linköping, Sweden; E.A. Stein, Medical Research Laboratories, Highland Heights, Kentucky, USA; C.W. White, University of Minnesota Medical School, Minneapolis, Minnesota, USA; M.D. Wilson, Health Core Inc., Newark, Delaware, USA.

Data Selection

Sources: Medical literature published in any language since 1983 on simvastatin, identified using AdisBase (a proprietary database of Adis International, Auckland, New Zealand) and Medline. Additional references were identified from the reference lists of published articles. Bibliographical information, including contributory unpublished data, was also requested from the company developing the drug.

Search strategy: AdisBase search terms were ‘Hyperlipidaemia’ or ‘Hypercholesterolaemia’ or ‘Arteriosclerosis’ and (‘guideline’ or ‘guideline-utilisation’ or ‘practice-guideline’ or ‘disease-management-programmes’ or ‘treatment-algorithms’ or ‘reviews-on-treatment’ or ‘cost-of-illness’) or ‘Simvastatin’ or ‘Epistatin’ or ‘MK-733’ or ‘Synvinolin’ or ‘Velastatin’ and (‘review’ or ‘clinical-study’). Medline search terms were ‘Hyperlipidaemia’ or ‘Hypercholesterolaemia’ or ‘Arteriosclerosis’ and (‘guidelines’ or ‘decision-making’ or ‘health-policy’ or ‘managed-care-programmes’ or ‘outcome-assessment-health-care’ or ‘clinical-protocols’ or ‘guideline in pt’ or ‘practice-guideline in pt’), or ‘Simvastatin’ or ‘Epistatin’ or ‘MK 733’ or ‘Synvinolin’ and ‘review in pt’. Searches were last updated 10 January 2000.

Selection: Studies in patients with dyslipidaemia who received simvastatin. Inclusion of studies was based mainly on the methods section of the trials. When available, large, well controlled trials with appropriate statistical methodology were preferred. Relevant pharmacodynamic, pharmacokinetic, pharmacoeconomic and epidemiological data are also included.

Index terms: simvastatin, dyslipidaemia, disease management, reviews on treatment.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hvizdos, K.M., Goa, K.L. Management of Dyslipidaemias. Dis-Manage-Health-Outcomes 7, 83–109 (2000). https://doi.org/10.2165/00115677-200007020-00004

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00115677-200007020-00004

Keywords

Search

Navigation