Skip to main content
Top
Published in: Drug Safety 5/2006

01-05-2006 | Review Article

Overcoming ‘Ageism’ Bias in the Treatment of Hypercholesterolaemia

A Review of Safety Issues with Statins in the Elderly

Author: Dr Terry A. Jacobson

Published in: Drug Safety | Issue 5/2006

Login to get access

Abstract

Atherosclerosis is a progressive, lifelong condition that is the leading cause of death among middle-aged and elderly individuals aged ≥65 years. Up to 80% of elderly patients are found to have evidence of obstructive coronary heart disease at autopsy. Demographic trends, including the advancing median age and life expectancy of Western societies, suggest that a large share of the burden of atherosclerotic plaque is likely to be borne by elderly individuals. These trends are in part due to increases in a number of chronic diseases associated with adverse cardiovascular outcomes, including metabolic syndrome, diabetes mellitus and chronic kidney disease. Because the elderly have a higher attributable risk of coronary heart disease as a result of hypercholesterolaemia, more coronary deaths and overall events can be prevented via treatment in this age group compared with younger persons with hypercholesterolaemia. The efficacy, safety and tolerability of HMG-CoA reductase inhibitors (statins) have been confirmed in randomised, controlled, multicentre trials involving large numbers of patients aged ≥65 years. Although muscle symptoms such as myalgia are relatively common adverse events, more severe signs of myolysis such as myopathy and rhabdomyolysis are rare, but their risk is elevated by conditions (e.g. concomitant medications) that increase the systemic exposure of these agents. Statins differ in their susceptibility to increases in systemic exposure, but most statins have been demonstrated to be well tolerated and safe when administered to elderly patients. These favourable clinical findings should help clinicians counter highly prevalent ‘ageism’ bias in statin prescribing, whereby elderly patients, particularly those at highest cardiovascular risk, are often denied the benefits of statins without any meaningful foundation.
Literature
1.
go back to reference Williams MA, Fleg JL, Ades PA, et al. Secondary prevention of coronary heart disease in the elderly (with emphasis on patients ≥75 years of age): an American Heart Association scientific statement from the Council on Clinical Cardiology Subcommittee on Exercise, Cardiac Rehabilitation, and Prevention. Circulation 2002; 105: 1735–43PubMedCrossRef Williams MA, Fleg JL, Ades PA, et al. Secondary prevention of coronary heart disease in the elderly (with emphasis on patients ≥75 years of age): an American Heart Association scientific statement from the Council on Clinical Cardiology Subcommittee on Exercise, Cardiac Rehabilitation, and Prevention. Circulation 2002; 105: 1735–43PubMedCrossRef
2.
go back to reference Frost PH, Davis BR, Burlando AJ, et al. Serum lipids and incidence of coronary heart disease: findings from the Systolic Hypertension in the Elderly Program (SHEP). Circulation 1996; 94: 2381–8PubMedCrossRef Frost PH, Davis BR, Burlando AJ, et al. Serum lipids and incidence of coronary heart disease: findings from the Systolic Hypertension in the Elderly Program (SHEP). Circulation 1996; 94: 2381–8PubMedCrossRef
3.
go back to reference Collins R. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet 2002; 360: 7–22CrossRef Collins R. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet 2002; 360: 7–22CrossRef
4.
go back to reference Pearson TA, Laurora I, Chu H, et al. The Lipid Treatment Assessment Project (L-TAP): a multicenter survey to evaluate the percentages of dyslipidemic patients receiving lipid-lowering therapy and achieving low-density lipoprotein cholesterol goals. Arch Intern Med 2000; 160: 459–67PubMedCrossRef Pearson TA, Laurora I, Chu H, et al. The Lipid Treatment Assessment Project (L-TAP): a multicenter survey to evaluate the percentages of dyslipidemic patients receiving lipid-lowering therapy and achieving low-density lipoprotein cholesterol goals. Arch Intern Med 2000; 160: 459–67PubMedCrossRef
5.
go back to reference Grundy SM, Cleeman JI, Rifkind BM, et al. Cholesterol lowering in the elderly population: coordinating Committee of the National Cholesterol Education Program. Arch Intern Med 1999; 159: 1670–8PubMedCrossRef Grundy SM, Cleeman JI, Rifkind BM, et al. Cholesterol lowering in the elderly population: coordinating Committee of the National Cholesterol Education Program. Arch Intern Med 1999; 159: 1670–8PubMedCrossRef
7.
go back to reference Kuller L, Borhani N, Furberg C, et al. Prevalence of subclinical atherosclerosis and cardiovascular disease and association with risk factors in the Cardiovascular Health Study. Am J Epidemiol 1994; 139: 1164–79PubMed Kuller L, Borhani N, Furberg C, et al. Prevalence of subclinical atherosclerosis and cardiovascular disease and association with risk factors in the Cardiovascular Health Study. Am J Epidemiol 1994; 139: 1164–79PubMed
8.
go back to reference Kagansky N, Levy S, Berner Y, et al. Cholesterol lowering in the older population: time for reassessment? QJM 2001; 94: 457–63PubMedCrossRef Kagansky N, Levy S, Berner Y, et al. Cholesterol lowering in the older population: time for reassessment? QJM 2001; 94: 457–63PubMedCrossRef
9.
go back to reference Batchelor WB, Jollis JG, Friesinger GC. The challenge of health care delivery to the elderly patient with cardiovascular disease: demographic, epidemiologic, fiscal, and health policy implications. Cardiol Clin 1999; 17: 1–15, viiPubMedCrossRef Batchelor WB, Jollis JG, Friesinger GC. The challenge of health care delivery to the elderly patient with cardiovascular disease: demographic, epidemiologic, fiscal, and health policy implications. Cardiol Clin 1999; 17: 1–15, viiPubMedCrossRef
10.
go back to reference US Census Bureau: US interim projections by age, sex, race, and Hispanic origin. 2004 [online]. Available from URL: http://www.census.gov/ipc/www/usinterimproj/ [Accessed 2005 January 25] US Census Bureau: US interim projections by age, sex, race, and Hispanic origin. 2004 [online]. Available from URL: http://​www.​census.​gov/​ipc/​www/​usinterimproj/​ [Accessed 2005 January 25]
11.
go back to reference Grundy SM. Age as a risk factor: you are as old as your arteries. Am J Cardiol 1999; 83: 1455–7, A7PubMedCrossRef Grundy SM. Age as a risk factor: you are as old as your arteries. Am J Cardiol 1999; 83: 1455–7, A7PubMedCrossRef
12.
go back to reference Rumberger JA, Sheedy PF, Breen JF, et al. Electron beam computed tomography and coronary artery disease: scanning for coronary artery calcification. Mayo Clin Proc 1996; 71: 369–77PubMedCrossRef Rumberger JA, Sheedy PF, Breen JF, et al. Electron beam computed tomography and coronary artery disease: scanning for coronary artery calcification. Mayo Clin Proc 1996; 71: 369–77PubMedCrossRef
13.
go back to reference Rumberger JA, Simons DB, Fitzpatrick LA, et al. Coronary artery calcium area by electron-beam computed tomography and coronary atherosclerotic plaque area: a histopathologic correlative study. Circulation 1995; 92: 2157–62PubMedCrossRef Rumberger JA, Simons DB, Fitzpatrick LA, et al. Coronary artery calcium area by electron-beam computed tomography and coronary atherosclerotic plaque area: a histopathologic correlative study. Circulation 1995; 92: 2157–62PubMedCrossRef
14.
go back to reference Rumberger JA, Schwartz RS, Simons DB, et al. Relation of coronary calcium determined by electron beam computed tomography and lumen narrowing determined by autopsy. Am J Cardiol 1994; 73: 1169–73PubMedCrossRef Rumberger JA, Schwartz RS, Simons DB, et al. Relation of coronary calcium determined by electron beam computed tomography and lumen narrowing determined by autopsy. Am J Cardiol 1994; 73: 1169–73PubMedCrossRef
15.
go back to reference Schmermund A, Baumgart D, Gorge G, et al. Measuring the effect of risk factors on coronary atherosclerosis: coronary calcium score versus angiographic disease severity. J Am Coll Cardiol 1998; 31: 1267–73PubMedCrossRef Schmermund A, Baumgart D, Gorge G, et al. Measuring the effect of risk factors on coronary atherosclerosis: coronary calcium score versus angiographic disease severity. J Am Coll Cardiol 1998; 31: 1267–73PubMedCrossRef
16.
go back to reference Guerci AD, Spadaro LA, Popma JJ, et al. Relation of coronary calcium score by electron beam computed tomography to arteriographic findings in asymptomatic and symptomatic adults. Am J Cardiol 1997; 79: 128–33PubMedCrossRef Guerci AD, Spadaro LA, Popma JJ, et al. Relation of coronary calcium score by electron beam computed tomography to arteriographic findings in asymptomatic and symptomatic adults. Am J Cardiol 1997; 79: 128–33PubMedCrossRef
17.
go back to reference Ford ES, Giles WH, Mokdad AH. Increasing prevalence of the metabolic syndrome among U.S. adults. Diabetes Care 2004; 27: 2444–9PubMedCrossRef Ford ES, Giles WH, Mokdad AH. Increasing prevalence of the metabolic syndrome among U.S. adults. Diabetes Care 2004; 27: 2444–9PubMedCrossRef
18.
go back to reference American Heart Association. Women and cardiovascular diseases: statistics. Statistical fact sheet: populations [online]. Available from URL: http://www.americanheart.org/presenter.jhtml?.identifier = 3000941 [Accessed 2005 August 3] American Heart Association. Women and cardiovascular diseases: statistics. Statistical fact sheet: populations [online]. Available from URL: http://​www.​americanheart.​org/​presenter.​jhtml?​.​identifier = 3000941 [Accessed 2005 August 3]
19.
go back to reference Mosca L, Appel LJ, Benjamin EJ, et al. Evidence-based guidelines for cardiovascular disease prevention in women. J Am Coll Cardiol 2004; 43: 900–21PubMedCrossRef Mosca L, Appel LJ, Benjamin EJ, et al. Evidence-based guidelines for cardiovascular disease prevention in women. J Am Coll Cardiol 2004; 43: 900–21PubMedCrossRef
20.
go back to reference Herrington DM, Vittinghoff E, Lin F, et al. Statin therapy, cardiovascular events, and total mortality in the Heart and Estrogen/Progestin Replacement Study (HERS). Circulation 2002; 105: 2962–7PubMedCrossRef Herrington DM, Vittinghoff E, Lin F, et al. Statin therapy, cardiovascular events, and total mortality in the Heart and Estrogen/Progestin Replacement Study (HERS). Circulation 2002; 105: 2962–7PubMedCrossRef
21.
go back to reference Welty FK. Preventing clinically evident coronary heart disease in the postmenopausal woman. Menopause 2004; 11: 484–94PubMedCrossRef Welty FK. Preventing clinically evident coronary heart disease in the postmenopausal woman. Menopause 2004; 11: 484–94PubMedCrossRef
22.
go back to reference Mosca L, Ferris A, Fabunmi R, et al. Tracking women’s awareness of heart disease: an American Heart Association national study. Circulation 2004; 109: 573–9PubMedCrossRef Mosca L, Ferris A, Fabunmi R, et al. Tracking women’s awareness of heart disease: an American Heart Association national study. Circulation 2004; 109: 573–9PubMedCrossRef
23.
go back to reference Anavekar NS, McMurray JJ, Velazquez EJ, et al. Relation between renal dysfunction and cardiovascular outcomes after myocardial infarction. N Engl J Med 2004; 351: 1285–95PubMedCrossRef Anavekar NS, McMurray JJ, Velazquez EJ, et al. Relation between renal dysfunction and cardiovascular outcomes after myocardial infarction. N Engl J Med 2004; 351: 1285–95PubMedCrossRef
24.
go back to reference Weiner DE, Sarnak MJ. Managing dyslipidemia in chronic kidney disease. J Gen Intern Med 2004; 19: 1045–52PubMedCrossRef Weiner DE, Sarnak MJ. Managing dyslipidemia in chronic kidney disease. J Gen Intern Med 2004; 19: 1045–52PubMedCrossRef
25.
go back to reference National Kidney Foundation. National Kidney Foundation’s Kidney Disease Outcome Quality Initiative (K/DOQI) clinical practice guidelines on managing dyslipidemias in chronic kidney disease. Am J Kidney Dis 2003; 41: S1–S92 National Kidney Foundation. National Kidney Foundation’s Kidney Disease Outcome Quality Initiative (K/DOQI) clinical practice guidelines on managing dyslipidemias in chronic kidney disease. Am J Kidney Dis 2003; 41: S1–S92
26.
go back to reference Sarnak MJ, Levey AS, Schoolwerth AC, et al. Kidney disease as a risk factor for development of cardiovascular disease: a statement from the American Heart Association Councils on Kidney in Cardiovascular Disease, High Blood Pressure Research, Clinical Cardiology, and Epidemiology and Prevention. Circulation 2003; 108: 2154–69PubMedCrossRef Sarnak MJ, Levey AS, Schoolwerth AC, et al. Kidney disease as a risk factor for development of cardiovascular disease: a statement from the American Heart Association Councils on Kidney in Cardiovascular Disease, High Blood Pressure Research, Clinical Cardiology, and Epidemiology and Prevention. Circulation 2003; 108: 2154–69PubMedCrossRef
27.
go back to reference Chobanian AV, Bakris GL, Black HR, et al. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA 2003; 289: 2560–72PubMedCrossRef Chobanian AV, Bakris GL, Black HR, et al. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA 2003; 289: 2560–72PubMedCrossRef
28.
go back to reference Adult Treatment Panel. Third report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III): final report. Circulation 2002; 106: 3143–421 Adult Treatment Panel. Third report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III): final report. Circulation 2002; 106: 3143–421
29.
go back to reference Fedder DO, Koro CE, L’Italien GJ. New National Cholesterol Education Program III guidelines for primary prevention lipid-lowering drug therapy: projected impact on the size, sex, and age distribution of the treatment-eligible population. Circulation 2002; 105: 152–6PubMedCrossRef Fedder DO, Koro CE, L’Italien GJ. New National Cholesterol Education Program III guidelines for primary prevention lipid-lowering drug therapy: projected impact on the size, sex, and age distribution of the treatment-eligible population. Circulation 2002; 105: 152–6PubMedCrossRef
30.
go back to reference Levy AR, O’Brien BJ, McMullen E, et al. Rapid increase in statins newly dispensed to Ontario seniors between 1994 and 2000. Can J Cardiol 2003; 19: 665–9PubMed Levy AR, O’Brien BJ, McMullen E, et al. Rapid increase in statins newly dispensed to Ontario seniors between 1994 and 2000. Can J Cardiol 2003; 19: 665–9PubMed
31.
go back to reference DeWilde S, Carey IM, Bremner SA, et al. Evolution of statin prescribing 1994-2001: a case of agism but not of sexism? Heart 2003; 89: 417–21PubMedCrossRef DeWilde S, Carey IM, Bremner SA, et al. Evolution of statin prescribing 1994-2001: a case of agism but not of sexism? Heart 2003; 89: 417–21PubMedCrossRef
32.
go back to reference Reid FD, Cook DG, Whincup PH. Use of statins in the secondary prevention of coronary heart disease: is treatment equitable? Heart 2002; 88: 15–9PubMedCrossRef Reid FD, Cook DG, Whincup PH. Use of statins in the secondary prevention of coronary heart disease: is treatment equitable? Heart 2002; 88: 15–9PubMedCrossRef
33.
go back to reference Ko DT, Mamdani M, Alter DA. Lipid-lowering therapy with statins in high-risk elderly patients: the treatment-risk paradox. JAMA 2004; 291: 1864–70PubMedCrossRef Ko DT, Mamdani M, Alter DA. Lipid-lowering therapy with statins in high-risk elderly patients: the treatment-risk paradox. JAMA 2004; 291: 1864–70PubMedCrossRef
34.
go back to reference Whincup PH, Emberson JR, Lennon L, et al. Low prevalence of lipid lowering drug use in older men with established coronary heart disease. Heart 2002; 88: 25–9PubMedCrossRef Whincup PH, Emberson JR, Lennon L, et al. Low prevalence of lipid lowering drug use in older men with established coronary heart disease. Heart 2002; 88: 25–9PubMedCrossRef
35.
go back to reference Lalouschek W, Lang W, Greisenegger S, et al. Determination of lipid profiles and use of statins in patients with ischemic stroke or transient ischemic attack. Stroke 2003; 34: 105–10PubMedCrossRef Lalouschek W, Lang W, Greisenegger S, et al. Determination of lipid profiles and use of statins in patients with ischemic stroke or transient ischemic attack. Stroke 2003; 34: 105–10PubMedCrossRef
36.
go back to reference Anderson KM, Castelli WP, Levy D. Cholesterol and mortality: 30 years of follow-up from the Framingham study. JAMA 1987; 257: 2176–80PubMedCrossRef Anderson KM, Castelli WP, Levy D. Cholesterol and mortality: 30 years of follow-up from the Framingham study. JAMA 1987; 257: 2176–80PubMedCrossRef
37.
go back to reference Volpato S, Leveille SG, Corti MC, et al. The value of serum albumin and high-density lipoprotein cholesterol in defining mortality risk in older persons with low serum cholesterol. J Am Geriatr Soc 2001; 49: 1142–7PubMedCrossRef Volpato S, Leveille SG, Corti MC, et al. The value of serum albumin and high-density lipoprotein cholesterol in defining mortality risk in older persons with low serum cholesterol. J Am Geriatr Soc 2001; 49: 1142–7PubMedCrossRef
38.
go back to reference Staessen J, Amery A, Birkenhager W, et al. Is a high serum cholesterol level associated with long survival in elderly hypertensives? J Hypertens 1990; 8: 755–61PubMedCrossRef Staessen J, Amery A, Birkenhager W, et al. Is a high serum cholesterol level associated with long survival in elderly hypertensives? J Hypertens 1990; 8: 755–61PubMedCrossRef
39.
go back to reference Kronmal RA, Cain KC, Ye Z, et al. Total serum cholesterol levels and mortality risk as a function of age: a report based on the Framingham data. Arch Intern Med 1993; 153: 1065–73PubMedCrossRef Kronmal RA, Cain KC, Ye Z, et al. Total serum cholesterol levels and mortality risk as a function of age: a report based on the Framingham data. Arch Intern Med 1993; 153: 1065–73PubMedCrossRef
40.
go back to reference Raiha I, Marniemi J, Puukka P, et al. Effect of serum lipids, lipoproteins, and apolipoproteins on vascular and nonvascular mortality in the elderly. Arterioscler Thromb Vasc Biol 1997; 17: 1224–32PubMedCrossRef Raiha I, Marniemi J, Puukka P, et al. Effect of serum lipids, lipoproteins, and apolipoproteins on vascular and nonvascular mortality in the elderly. Arterioscler Thromb Vasc Biol 1997; 17: 1224–32PubMedCrossRef
41.
go back to reference Weverling-Rijnsburger AW, Blauw GJ, Lagaay AM, et al. Total cholesterol and risk of mortality in the oldest old. Lancet 1997; 350: 1119–23PubMedCrossRef Weverling-Rijnsburger AW, Blauw GJ, Lagaay AM, et al. Total cholesterol and risk of mortality in the oldest old. Lancet 1997; 350: 1119–23PubMedCrossRef
42.
go back to reference LaRosa JC, Grundy SM, Waters DD, et al. Intensive lipid lowering with atorvastatin in patients with stable coronary disease. N Engl J Med 2005; 352: 1425–35PubMedCrossRef LaRosa JC, Grundy SM, Waters DD, et al. Intensive lipid lowering with atorvastatin in patients with stable coronary disease. N Engl J Med 2005; 352: 1425–35PubMedCrossRef
43.
go back to reference Chalasani N. Statins and hepatotoxicity: focus on patients with fatty liver. Persp Clin Hepatol 2005; 41: 690–5 Chalasani N. Statins and hepatotoxicity: focus on patients with fatty liver. Persp Clin Hepatol 2005; 41: 690–5
44.
go back to reference Bellosta S, Paoletti R, Corsini A. Safety of statins: focus on clinical pharmacokinetics and drug interactions. Circulation 2004; 109: III-50–III-57CrossRef Bellosta S, Paoletti R, Corsini A. Safety of statins: focus on clinical pharmacokinetics and drug interactions. Circulation 2004; 109: III-50–III-57CrossRef
45.
47.
go back to reference Sica DA, Gehr TW. Rhabdomyolysis and statin therapy: relevance to the elderly. Am J Geriatr Cardiol 2002; 11: 48–55PubMedCrossRef Sica DA, Gehr TW. Rhabdomyolysis and statin therapy: relevance to the elderly. Am J Geriatr Cardiol 2002; 11: 48–55PubMedCrossRef
48.
go back to reference Phillips PS, Haas RH, Bannykh S, et al. Statin-associated myopathy with normal creatine kinase levels. Ann Intern Med 2002; 137: 581–5PubMed Phillips PS, Haas RH, Bannykh S, et al. Statin-associated myopathy with normal creatine kinase levels. Ann Intern Med 2002; 137: 581–5PubMed
49.
go back to reference Staffa JA, Chang J, Green L. Cerivastatin and reports of fatal rhabdomyolysis. N Engl J Med 2002; 346: 539–40PubMedCrossRef Staffa JA, Chang J, Green L. Cerivastatin and reports of fatal rhabdomyolysis. N Engl J Med 2002; 346: 539–40PubMedCrossRef
50.
go back to reference AstraZeneca: Crestor® (rosuvastatin calcium) [online]. Available from URL: http://www.astrazeneca-us.com/pi/crestor.pdf [Accessed 2005 February 18] AstraZeneca: Crestor® (rosuvastatin calcium) [online]. Available from URL: http://​www.​astrazeneca-us.​com/​pi/​crestor.​pdf [Accessed 2005 February 18]
51.
go back to reference Jacobson TA. Comparative pharmacokinetic interaction profiles of pravastatin, simvastatin, and atorvastatin when coadministered with cytochrome P450 inhibitors. Am J Cardiol 2004; 94: 1140–6PubMedCrossRef Jacobson TA. Comparative pharmacokinetic interaction profiles of pravastatin, simvastatin, and atorvastatin when coadministered with cytochrome P450 inhibitors. Am J Cardiol 2004; 94: 1140–6PubMedCrossRef
52.
go back to reference Prueksaritanont T, Subramanian R, Fang X, et al. Glucuronidation of statins in animals and humans: a novel mechanism of statin lactonization. Drug Metab Dispos 2002; 30: 505–12PubMedCrossRef Prueksaritanont T, Subramanian R, Fang X, et al. Glucuronidation of statins in animals and humans: a novel mechanism of statin lactonization. Drug Metab Dispos 2002; 30: 505–12PubMedCrossRef
53.
go back to reference Graham DJ, Staffa JA, Shatin D, et al. Incidence of hospitalized rhabdomyolysis in patients treated with lipid-lowering drugs. JAMA 2004; 292: 2585–90PubMedCrossRef Graham DJ, Staffa JA, Shatin D, et al. Incidence of hospitalized rhabdomyolysis in patients treated with lipid-lowering drugs. JAMA 2004; 292: 2585–90PubMedCrossRef
54.
go back to reference Jones PH, Davidson MH. Reporting rate of rhabdomyolysis with fenofibrate + statin versus gemfibrozil + any statin. Am J Cardiol 2005; 95: 120–2PubMedCrossRef Jones PH, Davidson MH. Reporting rate of rhabdomyolysis with fenofibrate + statin versus gemfibrozil + any statin. Am J Cardiol 2005; 95: 120–2PubMedCrossRef
55.
go back to reference Psaty BM, Furberg CD, Ray WA, et al. Potential for conflict of interest in the evaluation of suspected adverse drug reactions: use of cerivastatin and risk of rhabdomyolysis. JAMA 2004; 292: 2622–31PubMedCrossRef Psaty BM, Furberg CD, Ray WA, et al. Potential for conflict of interest in the evaluation of suspected adverse drug reactions: use of cerivastatin and risk of rhabdomyolysis. JAMA 2004; 292: 2622–31PubMedCrossRef
56.
go back to reference Insull W Jr, Isaacsohn J, Kwiterovich P. Efficacy and safety of cerivastatin 0.8mg in patients with hypercholesterolaemia: the pivotal placebo-controlled clinical trial. Cerivastatin Study Group. J Int Med Res 2000; 28: 47–68PubMed Insull W Jr, Isaacsohn J, Kwiterovich P. Efficacy and safety of cerivastatin 0.8mg in patients with hypercholesterolaemia: the pivotal placebo-controlled clinical trial. Cerivastatin Study Group. J Int Med Res 2000; 28: 47–68PubMed
57.
go back to reference Law MR, Wald NJ, Rudnicka AR. Quantifying effect of statins on low density lipoprotein cholesterol, ischaemic heart disease, and stroke: systematic review and meta-analysis. BMJ 2003; 326: 1423–9PubMedCrossRef Law MR, Wald NJ, Rudnicka AR. Quantifying effect of statins on low density lipoprotein cholesterol, ischaemic heart disease, and stroke: systematic review and meta-analysis. BMJ 2003; 326: 1423–9PubMedCrossRef
58.
go back to reference Colhoun HM, Betteridge DJ, Durrington PN, et al. Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): multicentre randomised placebo-controlled trial. Lancet 2004; 364: 685–96PubMedCrossRef Colhoun HM, Betteridge DJ, Durrington PN, et al. Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): multicentre randomised placebo-controlled trial. Lancet 2004; 364: 685–96PubMedCrossRef
59.
go back to reference Sever PS, Dahlof B, Poulter NR, et al. Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trial-Lipid Lowering Arm (ASCOT-LLA): a multicentre randomised controlled trial. Lancet 2003; 361: 1149–58PubMedCrossRef Sever PS, Dahlof B, Poulter NR, et al. Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trial-Lipid Lowering Arm (ASCOT-LLA): a multicentre randomised controlled trial. Lancet 2003; 361: 1149–58PubMedCrossRef
60.
go back to reference Downs JR, 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. Air Force/Texas Coronary Atherosclerosis Prevention Study. JAMA 1998; 279: 1615–22PubMedCrossRef Downs JR, 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. Air Force/Texas Coronary Atherosclerosis Prevention Study. JAMA 1998; 279: 1615–22PubMedCrossRef
61.
go back to reference Bradford RH, Shear CL, Chremos AN, et al. Expanded Clinical Evaluation of Lovastatin (EXCEL) study results: two-year efficacy and safety follow-up. Am J Cardiol 1994; 74: 667–73PubMedCrossRef Bradford RH, Shear CL, Chremos AN, et al. Expanded Clinical Evaluation of Lovastatin (EXCEL) study results: two-year efficacy and safety follow-up. Am J Cardiol 1994; 74: 667–73PubMedCrossRef
62.
go back to reference Shepherd J, Blauw GJ, Murphy MB, et al. Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial. Lancet 2002; 360: 1623–30PubMedCrossRef Shepherd J, Blauw GJ, Murphy MB, et al. Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial. Lancet 2002; 360: 1623–30PubMedCrossRef
63.
go back to reference Downs JR, Clearfield M, Tyroler HA, et al. Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TeXCAPS): additional perspectives on tolerability of long-term treatment with lovastatin. Am J Cardiol 2001; 87: 1074–9PubMedCrossRef Downs JR, Clearfield M, Tyroler HA, et al. Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TeXCAPS): additional perspectives on tolerability of long-term treatment with lovastatin. Am J Cardiol 2001; 87: 1074–9PubMedCrossRef
64.
go back to reference Shepherd J, Cobbe SM, Ford I, et al. Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. West of Scotland Coronary Prevention Study Group. N Engl J Med 1995; 333: 1301–7PubMedCrossRef Shepherd J, Cobbe SM, Ford I, et al. Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. West of Scotland Coronary Prevention Study Group. N Engl J Med 1995; 333: 1301–7PubMedCrossRef
65.
go back to reference Salonen R, Nyyssonen K, Porkkala E, et al. Kuopio Atherosclerosis Prevention Study (KAPS). A population-based primary preventive trial of the effect of L D L lowering on atherosclerotic progression in carotid and femoral arteries. Circulation 1995; 92: 1758–64PubMedCrossRef Salonen R, Nyyssonen K, Porkkala E, et al. Kuopio Atherosclerosis Prevention Study (KAPS). A population-based primary preventive trial of the effect of L D L lowering on atherosclerotic progression in carotid and femoral arteries. Circulation 1995; 92: 1758–64PubMedCrossRef
66.
go back to reference Byington RP, Jukema JW, Salonen JT, et al. Reduction in cardiovascular events during pravastatin therapy: pooled analysis of clinical events of the Pravastatin Atherosclerosis Intervention Program. Circulation 1995; 92: 2419–25PubMedCrossRef Byington RP, Jukema JW, Salonen JT, et al. Reduction in cardiovascular events during pravastatin therapy: pooled analysis of clinical events of the Pravastatin Atherosclerosis Intervention Program. Circulation 1995; 92: 2419–25PubMedCrossRef
67.
go back to reference Schwartz GG, Olsson AG, Ezekowitz MD, et al. Effects of atorvastatin on early recurrent ischemic events in acute coronary syndromes: the MIRACL study: a randomized controlled trial. JAMA 2001; 285: 1711–8PubMedCrossRef Schwartz GG, Olsson AG, Ezekowitz MD, et al. Effects of atorvastatin on early recurrent ischemic events in acute coronary syndromes: the MIRACL study: a randomized controlled trial. JAMA 2001; 285: 1711–8PubMedCrossRef
68.
go back to reference Waters DD, Schwartz GG, Olsson AG, et al. Effects of atorvastatin on stroke in patients with unstable angina or non-Q-wave myocardial infarction: a Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) substudy. Circulation 2002; 106: 1690–5PubMedCrossRef Waters DD, Schwartz GG, Olsson AG, et al. Effects of atorvastatin on stroke in patients with unstable angina or non-Q-wave myocardial infarction: a Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) substudy. Circulation 2002; 106: 1690–5PubMedCrossRef
69.
go back to reference Athyros VG, Papageorgiou AA, Mercouris BR, et al. Treatment with atorvastatin to the National Cholesterol Educational Program goal versus ‘usual’ care in secondary coronary heart disease prevention: the GREek Atorvastatin and Coronaryheart-disease Evaluation (GREACE) study. Curr Med Res Opin 2002; 18: 220–8PubMedCrossRef Athyros VG, Papageorgiou AA, Mercouris BR, et al. Treatment with atorvastatin to the National Cholesterol Educational Program goal versus ‘usual’ care in secondary coronary heart disease prevention: the GREek Atorvastatin and Coronaryheart-disease Evaluation (GREACE) study. Curr Med Res Opin 2002; 18: 220–8PubMedCrossRef
70.
go back to reference Cannon CP, Braunwald E, McCabe CH, et al. Intensive versus moderate lipid lowering with statins after acute coronary syndromes. N Engl J Med 2004; 350: 1495–504PubMedCrossRef Cannon CP, Braunwald E, McCabe CH, et al. Intensive versus moderate lipid lowering with statins after acute coronary syndromes. N Engl J Med 2004; 350: 1495–504PubMedCrossRef
71.
go back to reference Serruys PW, de Feyter P, Macaya C, et al. Fluvastatin for prevention of cardiac events following successful first percutaneous coronary intervention: a randomized controlled trial. JAMA 2002; 287: 3215–22PubMedCrossRef Serruys PW, de Feyter P, Macaya C, et al. Fluvastatin for prevention of cardiac events following successful first percutaneous coronary intervention: a randomized controlled trial. JAMA 2002; 287: 3215–22PubMedCrossRef
72.
go back to reference Herd JA. The Lipoprotein and Coronary Atherosclerosis Study (LCAS): lipid and metabolic factors related to atheroma and clinical events. Am J Med 1998; 104: 42S–9SPubMedCrossRef Herd JA. The Lipoprotein and Coronary Atherosclerosis Study (LCAS): lipid and metabolic factors related to atheroma and clinical events. Am J Med 1998; 104: 42S–9SPubMedCrossRef
73.
go back to reference Herd JA, Ballantyne CM, Farmer JA, et al. Effects of fluvastatin on coronary atherosclerosis in patients with mild to moderate cholesterol elevations (Lipoprotein and Coronary Atherosclerosis Study [LCAS]). Am J Cardiol 1997; 80: 278–86PubMedCrossRef Herd JA, Ballantyne CM, Farmer JA, et al. Effects of fluvastatin on coronary atherosclerosis in patients with mild to moderate cholesterol elevations (Lipoprotein and Coronary Atherosclerosis Study [LCAS]). Am J Cardiol 1997; 80: 278–86PubMedCrossRef
74.
go back to reference Riegger G, Abletshauser C, Ludwig M, et al. The effect of fluvastatin on cardiac events in patients with symptomatic coronary artery disease during one year of treatment. Atherosclerosis 1999; 144: 263–70PubMedCrossRef Riegger G, Abletshauser C, Ludwig M, et al. The effect of fluvastatin on cardiac events in patients with symptomatic coronary artery disease during one year of treatment. Atherosclerosis 1999; 144: 263–70PubMedCrossRef
75.
go back to reference Post-CABG Investigators. 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. The Post Coronary Artery Bypass Graft Trial Investigators. N Engl J Med 1997; 336: 153–62 Post-CABG Investigators. 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. The Post Coronary Artery Bypass Graft Trial Investigators. N Engl J Med 1997; 336: 153–62
76.
go back to reference Furberg CD, Adams HP Jr, Applegate WB, et al. Effect of lovastatin on early carotid atherosclerosis and cardiovascular events. Asymptomatic Carotid Artery Progression Study (ACAPS) Research Group. Circulation 1994; 90: 1679–87PubMedCrossRef Furberg CD, Adams HP Jr, Applegate WB, et al. Effect of lovastatin on early carotid atherosclerosis and cardiovascular events. Asymptomatic Carotid Artery Progression Study (ACAPS) Research Group. Circulation 1994; 90: 1679–87PubMedCrossRef
77.
go back to reference Weintraub WS, Boccuzzi SJ, Klein JL, et al. Lack of effect of lovastatin on restenosis after coronary angioplasty. Lovastatin Restenosis Trial Study Group. N Engl J Med 1994; 331: 1331–7PubMedCrossRef Weintraub WS, Boccuzzi SJ, Klein JL, et al. Lack of effect of lovastatin on restenosis after coronary angioplasty. Lovastatin Restenosis Trial Study Group. N Engl J Med 1994; 331: 1331–7PubMedCrossRef
78.
go back to reference 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. The Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study Group. N Engl J Med 1998; 339: 1349–57 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. The Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study Group. N Engl J Med 1998; 339: 1349–57
79.
go back to reference White HD, Simes RJ, Anderson NE, et al. Pravastatin therapy and the risk of stroke. N Engl J Med 2000; 343: 317–26PubMedCrossRef White HD, Simes RJ, Anderson NE, et al. Pravastatin therapy and the risk of stroke. N Engl J Med 2000; 343: 317–26PubMedCrossRef
80.
go back to reference Pfeffer MA, Keech A, Sacks FM, et al. Safety and tolerability of pravastatin in long-term clinical trials: Prospective Pravastatin Pooling (PPP) Project. Circulation 2002; 105: 2341–6PubMedCrossRef Pfeffer MA, Keech A, Sacks FM, et al. Safety and tolerability of pravastatin in long-term clinical trials: Prospective Pravastatin Pooling (PPP) Project. Circulation 2002; 105: 2341–6PubMedCrossRef
81.
go back to reference Sacks FM, Pfeffer MA, Moye LA, et al. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. Cholesterol and Recurrent Events Trial investigators. N Engl J Med 1996; 335: 1001–9PubMedCrossRef Sacks FM, Pfeffer MA, Moye LA, et al. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. Cholesterol and Recurrent Events Trial investigators. N Engl J Med 1996; 335: 1001–9PubMedCrossRef
82.
go back to reference Byington RP, Davis BR, Plehn JF, et al. Reduction of stroke events with pravastatin: the Prospective Pravastatin Pooling (PPP) Project. Circulation 2001; 103: 387–92PubMedCrossRef Byington RP, Davis BR, Plehn JF, et al. Reduction of stroke events with pravastatin: the Prospective Pravastatin Pooling (PPP) Project. Circulation 2001; 103: 387–92PubMedCrossRef
83.
go back to reference PMSG Investigators. Effects of pravastatin in patients with serum total cholesterol levels from 5.2 to 7.8 mmol/liter (200 to 300 mg/dl) plus two additional atherosclerotic risk factors. The Pravastatin Multinational Study Group for Cardiac Risk Patients. Am J Cardiol 1993; 72: 1031–7 PMSG Investigators. Effects of pravastatin in patients with serum total cholesterol levels from 5.2 to 7.8 mmol/liter (200 to 300 mg/dl) plus two additional atherosclerotic risk factors. The Pravastatin Multinational Study Group for Cardiac Risk Patients. Am J Cardiol 1993; 72: 1031–7
84.
go back to reference 4S Investigators. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet 1994; 344: 1383–9 4S Investigators. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet 1994; 344: 1383–9
85.
go back to reference MAAS Investigators. Effect of simvastatin on coronary atheroma: the Multicentre Anti-Atheroma Study (MAAS). Lancet 1994; 344: 633–8 MAAS Investigators. Effect of simvastatin on coronary atheroma: the Multicentre Anti-Atheroma Study (MAAS). Lancet 1994; 344: 633–8
86.
go back to reference de Lemos JA, Blazing MA, Wiviott SD, et al. Early intensive vs a delayed conservative simvastatin strategy in patients with acute coronary syndromes: phase Z of the A to Z trial. JAMA 2004; 292: 1307–16PubMedCrossRef de Lemos JA, Blazing MA, Wiviott SD, et al. Early intensive vs a delayed conservative simvastatin strategy in patients with acute coronary syndromes: phase Z of the A to Z trial. JAMA 2004; 292: 1307–16PubMedCrossRef
87.
go back to reference Holdaas H, Fellstrom B, Jardine AG, et al. Effect of fluvastatin on cardiac outcomes in renal transplant recipients: a multicentre, randomised, placebo-controlled trial. Lancet 2003; 361: 2024–31PubMedCrossRef Holdaas H, Fellstrom B, Jardine AG, et al. Effect of fluvastatin on cardiac outcomes in renal transplant recipients: a multicentre, randomised, placebo-controlled trial. Lancet 2003; 361: 2024–31PubMedCrossRef
88.
90.
go back to reference Perger L, Kohler M, Fattinger K, et al. Fatal liver failure with atorvastatin [letter]. J Hepatol 2003; 39: 1096–107CrossRef Perger L, Kohler M, Fattinger K, et al. Fatal liver failure with atorvastatin [letter]. J Hepatol 2003; 39: 1096–107CrossRef
91.
go back to reference Tolman KG. Defining patient risk from expanded preventive therapies. Am J Cardiol 2000; 85: 15E–9EPubMedCrossRef Tolman KG. Defining patient risk from expanded preventive therapies. Am J Cardiol 2000; 85: 15E–9EPubMedCrossRef
92.
go back to reference Russo MW, Galanko JA, Shrestha R, et al. Liver transplantation from drug induced liver injury in the United States. Liver Transpl 2004; 10: 1018–23PubMedCrossRef Russo MW, Galanko JA, Shrestha R, et al. Liver transplantation from drug induced liver injury in the United States. Liver Transpl 2004; 10: 1018–23PubMedCrossRef
93.
go back to reference Graziadei IW, Obermoser GE, Sepp NT, et al. Drug-induced lupus-like syndrome associated severe autoimmune hepatitis. Lupus 2003; 12: 409–12PubMedCrossRef Graziadei IW, Obermoser GE, Sepp NT, et al. Drug-induced lupus-like syndrome associated severe autoimmune hepatitis. Lupus 2003; 12: 409–12PubMedCrossRef
94.
go back to reference Pelli N, Setti M, Ceppa P, et al. Autoimmune hepatitis revealed by atorvastatin. Eur J Gastro Hepatol 2003; 15: 921–4CrossRef Pelli N, Setti M, Ceppa P, et al. Autoimmune hepatitis revealed by atorvastatin. Eur J Gastro Hepatol 2003; 15: 921–4CrossRef
95.
go back to reference Parke-Davis. Lipitor® (atorvastatin calcium): US prescribing information [online]. Available from URL: http://www.pfizer.com/download/uspi_lipitor.pdf. [Accessed 2005 February 18] Parke-Davis. Lipitor® (atorvastatin calcium): US prescribing information [online]. Available from URL: http://​www.​pfizer.​com/​download/​uspi_​lipitor.​pdf.​ [Accessed 2005 February 18]
96.
go back to reference Novartis. Lescol®, Lescol® XL (fluvastatin sodium): US prescribing information [online]. Available from URL: http://www.pharma.us.novartis.com/product/pi/pdf/Lescol.pdf. [Accessed 2005 February 18] Novartis. Lescol®, Lescol® XL (fluvastatin sodium): US prescribing information [online]. Available from URL: http://​www.​pharma.​us.​novartis.​com/​product/​pi/​pdf/​Lescol.​pdf.​ [Accessed 2005 February 18]
97.
go back to reference Farnier M, Bortolini M, Salko T, et al. Frequency of creatine kinase elevation during treatment with fluvastatin in combination with fibrates (bezafibrate, fenofibrate, or gemfibrozil). Am J Cardiol 2003; 91: 238–40PubMedCrossRef Farnier M, Bortolini M, Salko T, et al. Frequency of creatine kinase elevation during treatment with fluvastatin in combination with fibrates (bezafibrate, fenofibrate, or gemfibrozil). Am J Cardiol 2003; 91: 238–40PubMedCrossRef
98.
go back to reference Pauciullo P, Borgnino C, Paoletti R, et al. Efficacy and safety of a combination of fluvastatin and bezafibrate in patients with mixed hyperlipidaemia (FACT study). Atherosclerosis 2000; 150: 429–36PubMedCrossRef Pauciullo P, Borgnino C, Paoletti R, et al. Efficacy and safety of a combination of fluvastatin and bezafibrate in patients with mixed hyperlipidaemia (FACT study). Atherosclerosis 2000; 150: 429–36PubMedCrossRef
99.
go back to reference Ballantyne CM, McKenney J, Trippe BS. Efficacy and safety of an extended-release formulation of fluvastatin for once-daily treatment of primary hypercholesterolemia. Am J Cardiol 2000; 86: 759–63PubMedCrossRef Ballantyne CM, McKenney J, Trippe BS. Efficacy and safety of an extended-release formulation of fluvastatin for once-daily treatment of primary hypercholesterolemia. Am J Cardiol 2000; 86: 759–63PubMedCrossRef
100.
go back to reference Bruckert E, Lievre M, Giral P, et al. Short-term efficacy and safety of extended-release fluvastatin in a large cohort of elderly patients. Am J Geriatr Cardiol 2003; 12: 225–31PubMed Bruckert E, Lievre M, Giral P, et al. Short-term efficacy and safety of extended-release fluvastatin in a large cohort of elderly patients. Am J Geriatr Cardiol 2003; 12: 225–31PubMed
101.
go back to reference Lye M, Valacio R, Reckless JP, et al. Elderly patients with hypercholesterolaemia: a double-blind study of the efficacy, safety and tolerability of fluvastatin. Coron Artery Dis 1998; 9: 583–90PubMedCrossRef Lye M, Valacio R, Reckless JP, et al. Elderly patients with hypercholesterolaemia: a double-blind study of the efficacy, safety and tolerability of fluvastatin. Coron Artery Dis 1998; 9: 583–90PubMedCrossRef
102.
go back to reference Bruckert E, Hayem G, Dejager S, et al. Risk of muscular symptoms with high dosage statin therapy in 7924 hyperlipidemic patients in French clinical practice. American College of Cardiology; 2005 March 6-9; Orlando, FL Bruckert E, Hayem G, Dejager S, et al. Risk of muscular symptoms with high dosage statin therapy in 7924 hyperlipidemic patients in French clinical practice. American College of Cardiology; 2005 March 6-9; Orlando, FL
103.
go back to reference Serruys PW, De Feyter PJ, Benghozi R, et al. The Lescol® Intervention Prevention Study (LIPS): a double-blind, placebo-controlled, randomized trial of the long-term effects of fluvastatin after successful transcatheter therapy in patients with coronary heart disease. Int J Cardiovasc Intervent 2001; 4: 165–72PubMed Serruys PW, De Feyter PJ, Benghozi R, et al. The Lescol® Intervention Prevention Study (LIPS): a double-blind, placebo-controlled, randomized trial of the long-term effects of fluvastatin after successful transcatheter therapy in patients with coronary heart disease. Int J Cardiovasc Intervent 2001; 4: 165–72PubMed
104.
go back to reference Benghozi R, Bortolini M, Jia Y, et al. Frequency of creatine kinase elevation during treatment with fluvastatin. Am J Cardiol 2002; 89: 231–3PubMedCrossRef Benghozi R, Bortolini M, Jia Y, et al. Frequency of creatine kinase elevation during treatment with fluvastatin. Am J Cardiol 2002; 89: 231–3PubMedCrossRef
105.
go back to reference Bristol-Myers Squibb: Pravachol® (pravastatin sodium). US prescribing information [online]. Available from URL: http://www.bms.com/cgi-bin/anybin.pl?sql=select%20PPI%20from%20TB_PRODUCT_PPI%20where%20PPI_SEQ=56 [Accessed 2005 February 18] Bristol-Myers Squibb: Pravachol® (pravastatin sodium). US prescribing information [online]. Available from URL: http://​www.​bms.​com/​cgi-bin/​anybin.​pl?​sql=​select%20PPI%20from%20TB_PRODUCT_PPI%20where%20PPI_SEQ=56 [Accessed 2005 February 18]
106.
go back to reference Bjerre LM, LeLorier J. Do statins cause cancer? A meta-analysis of large randomized clinical trials. Am J Med 2001; 110: 716–23PubMedCrossRef Bjerre LM, LeLorier J. Do statins cause cancer? A meta-analysis of large randomized clinical trials. Am J Med 2001; 110: 716–23PubMedCrossRef
107.
go back to reference Hunt D, Young P, Simes J, et al. Benefits of pravastatin on cardiovascular events and mortality in older patients with coronary heart disease are equal to or exceed those seen in younger patients: results from the LIPID trial. Ann Intern Med 2001; 134: 931–40PubMed Hunt D, Young P, Simes J, et al. Benefits of pravastatin on cardiovascular events and mortality in older patients with coronary heart disease are equal to or exceed those seen in younger patients: results from the LIPID trial. Ann Intern Med 2001; 134: 931–40PubMed
108.
go back to reference Shepherd J, Hunninghake DB, Stein EA, et al. Safety of rosuvastatin. Am J Cardiol 2004; 94: 882–8PubMedCrossRef Shepherd J, Hunninghake DB, Stein EA, et al. Safety of rosuvastatin. Am J Cardiol 2004; 94: 882–8PubMedCrossRef
109.
go back to reference Jones PH, Davidson MH, Stein EA, et al. Comparison of the efficacy and safety of rosuvastatin versus atorvastatin, simvastatin, and pravastatin across doses (STELLAR* Trial). Am J Cardiol 2003; 92: 152–60PubMedCrossRef Jones PH, Davidson MH, Stein EA, et al. Comparison of the efficacy and safety of rosuvastatin versus atorvastatin, simvastatin, and pravastatin across doses (STELLAR* Trial). Am J Cardiol 2003; 92: 152–60PubMedCrossRef
110.
go back to reference Martin PD, Dane AL, Nwose OM, et al. No effect of age or gender on the pharmacokinetics of rosuvastatin: a new HMGCoA reductase inhibitor. J Clin Pharmacol 2002; 42: 1116–21PubMedCrossRef Martin PD, Dane AL, Nwose OM, et al. No effect of age or gender on the pharmacokinetics of rosuvastatin: a new HMGCoA reductase inhibitor. J Clin Pharmacol 2002; 42: 1116–21PubMedCrossRef
111.
go back to reference Galson SK for the US Food and Drug Administration. Rejection of Public Citizen petition (cited 3/11/05) Docket No. 2004P-0113CP1 [online]. Available from URL: http://www.fda.gov/cder/drug/infopage/rosuvastatin/crestor_CP.pdf. [Accessed 2005 August 30] Galson SK for the US Food and Drug Administration. Rejection of Public Citizen petition (cited 3/11/05) Docket No. 2004P-0113CP1 [online]. Available from URL: http://​www.​fda.​gov/​cder/​drug/​infopage/​rosuvastatin/​crestor_​CP.​pdf.​ [Accessed 2005 August 30]
112.
go back to reference Brewer HB. Benefit-risk assessment of rosuvastatin 10 to 40 milligrams. Am J Cardiol 2003; 92: 23K–9KPubMedCrossRef Brewer HB. Benefit-risk assessment of rosuvastatin 10 to 40 milligrams. Am J Cardiol 2003; 92: 23K–9KPubMedCrossRef
113.
go back to reference Vidt DG, Cressman MD, Harris S, et al. Rosuvastatin-induced arrest in progression of renal disease. Cardiology 2004; 102: 52–60PubMedCrossRef Vidt DG, Cressman MD, Harris S, et al. Rosuvastatin-induced arrest in progression of renal disease. Cardiology 2004; 102: 52–60PubMedCrossRef
114.
go back to reference Alsheikh-Ali A, Ambrose MS, Kuvin JT, et al. The safety of rosuvastatin as used in common clinical practice: a postmarketing analysis. Circulation 2005; 111: 3051–7PubMedCrossRef Alsheikh-Ali A, Ambrose MS, Kuvin JT, et al. The safety of rosuvastatin as used in common clinical practice: a postmarketing analysis. Circulation 2005; 111: 3051–7PubMedCrossRef
115.
116.
go back to reference Merck. Zocor® (simvastatin): US prescribing information [online]. Available from URL: http://www.zocor.com/zocor/shared/documents/english/pi.pdf [Accessed 2005 February 18] Merck. Zocor® (simvastatin): US prescribing information [online]. Available from URL: http://​www.​zocor.​com/​zocor/​shared/​documents/​english/​pi.​pdf [Accessed 2005 February 18]
117.
go back to reference Miettinen TA, Pyorala 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; 96: 4211–8PubMedCrossRef Miettinen TA, Pyorala 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; 96: 4211–8PubMedCrossRef
118.
go back to reference Lipka L, Sager P, Strony J, et al. Efficacy and safety of coadministration of ezetimibe and statins in elderly patients with primary hypercholesterolaemia. Drugs Aging 2004; 21: 1025–32PubMedCrossRef Lipka L, Sager P, Strony J, et al. Efficacy and safety of coadministration of ezetimibe and statins in elderly patients with primary hypercholesterolaemia. Drugs Aging 2004; 21: 1025–32PubMedCrossRef
119.
go back to reference Abbott TriCor® (fenofibrate): US prescribing information [online]. Available from URL: http://www.rxabbott.com/pdf/tricorpi.pdf [Accessed 2005 March 25] Abbott TriCor® (fenofibrate): US prescribing information [online]. Available from URL: http://​www.​rxabbott.​com/​pdf/​tricorpi.​pdf [Accessed 2005 March 25]
120.
go back to reference Omar MA, Wilson JP. FDA adverse event reports on statin-associated rhabdomyolysis. Ann Pharmacother 2002; 36: 288–95PubMedCrossRef Omar MA, Wilson JP. FDA adverse event reports on statin-associated rhabdomyolysis. Ann Pharmacother 2002; 36: 288–95PubMedCrossRef
121.
go back to reference Corsini A. The safety of HMG-CoA reductase inhibitors in special populations at high cardiovascular risk. Cardiovasc Drugs Ther 2003; 17: 265–85PubMedCrossRef Corsini A. The safety of HMG-CoA reductase inhibitors in special populations at high cardiovascular risk. Cardiovasc Drugs Ther 2003; 17: 265–85PubMedCrossRef
122.
go back to reference Chang JT, Staffa JA, Parks M, et al. Rhabdomyolysis with HMG-CoA reductase inhibitors and gemfibrozil combination therapy. Pharmacoepidemiol Drug Saf 2004; 13: 417–26PubMedCrossRef Chang JT, Staffa JA, Parks M, et al. Rhabdomyolysis with HMG-CoA reductase inhibitors and gemfibrozil combination therapy. Pharmacoepidemiol Drug Saf 2004; 13: 417–26PubMedCrossRef
123.
go back to reference Papadakis JA, Ganotakis ES, Jagroop IA, et al. Statin + fibrate combination therapy fluvastatin with bezafibrate or ciprofibrate in high risk patients with vascular disease. Int J Cardiol 1999; 69: 237–44PubMedCrossRef Papadakis JA, Ganotakis ES, Jagroop IA, et al. Statin + fibrate combination therapy fluvastatin with bezafibrate or ciprofibrate in high risk patients with vascular disease. Int J Cardiol 1999; 69: 237–44PubMedCrossRef
124.
go back to reference Prueksaritanont T, Tang C, Qiu Y, et al. Effects of fibrates on metabolism of statins in human hepatocytes. Drug Metab Dispos 2002; 30(11): 1280–7PubMedCrossRef Prueksaritanont T, Tang C, Qiu Y, et al. Effects of fibrates on metabolism of statins in human hepatocytes. Drug Metab Dispos 2002; 30(11): 1280–7PubMedCrossRef
125.
go back to reference Fischer V, Johanson L, Heitz F, et al. The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor fluvastatin: effect on human cytochrome P-450 and implications for metabolic drug interactions. Drug Metab Dispos 1999; 27: 410–6PubMed Fischer V, Johanson L, Heitz F, et al. The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor fluvastatin: effect on human cytochrome P-450 and implications for metabolic drug interactions. Drug Metab Dispos 1999; 27: 410–6PubMed
126.
go back to reference Kyrklund C, Backman JT, Neuvonen M, et al. Gemfibrozil increases plasma pravastatin concentrations and reduces pravastatin renal clearance. Clin Pharmacol Ther 2003; 73: 538–44PubMedCrossRef Kyrklund C, Backman JT, Neuvonen M, et al. Gemfibrozil increases plasma pravastatin concentrations and reduces pravastatin renal clearance. Clin Pharmacol Ther 2003; 73: 538–44PubMedCrossRef
127.
go back to reference Schneck DW, Birmingham BK, Zalikowski JA, et al. The effect of gemfibrozil on the pharmacokinetics of rosuvastatin. Clin Pharmacol Ther 2004; 75: 455–63PubMedCrossRef Schneck DW, Birmingham BK, Zalikowski JA, et al. The effect of gemfibrozil on the pharmacokinetics of rosuvastatin. Clin Pharmacol Ther 2004; 75: 455–63PubMedCrossRef
128.
go back to reference Spence JD, Munoz CE, Hendricks L, et al. Pharmacokinetics of the combination of fluvastatin and gemfibrozil. Am J Cardiol 1995; 76: 80A–3APubMedCrossRef Spence JD, Munoz CE, Hendricks L, et al. Pharmacokinetics of the combination of fluvastatin and gemfibrozil. Am J Cardiol 1995; 76: 80A–3APubMedCrossRef
129.
go back to reference Backman JT, Kyrklund C, Kivisto KT, et al. Plasma concentrations of active simvastatin acid are increased by gemfibrozil. Clin Pharmacol Ther 2000; 68: 122–9PubMedCrossRef Backman JT, Kyrklund C, Kivisto KT, et al. Plasma concentrations of active simvastatin acid are increased by gemfibrozil. Clin Pharmacol Ther 2000; 68: 122–9PubMedCrossRef
130.
go back to reference Wiklund O, Angelin B, Bergman M, et al. Pravastatin and gemfibrozil alone and in combination for the treatment of hypercholesterolemia. Am J Med 1993; 94: 13–20PubMedCrossRef Wiklund O, Angelin B, Bergman M, et al. Pravastatin and gemfibrozil alone and in combination for the treatment of hypercholesterolemia. Am J Med 1993; 94: 13–20PubMedCrossRef
131.
go back to reference Davidson MH. Combination therapy for dyslipidemia: safety and regulatory considerations. Am J Cardiol 2002; 90: 50K–60KPubMedCrossRef Davidson MH. Combination therapy for dyslipidemia: safety and regulatory considerations. Am J Cardiol 2002; 90: 50K–60KPubMedCrossRef
132.
go back to reference Brown BG, Zhao XQ, Chait A, et al. Simvastatin and niacin, antioxidant vitamins, or the combination for the prevention of coronary disease. N Engl J Med 2001; 345: 1583–92PubMedCrossRef Brown BG, Zhao XQ, Chait A, et al. Simvastatin and niacin, antioxidant vitamins, or the combination for the prevention of coronary disease. N Engl J Med 2001; 345: 1583–92PubMedCrossRef
133.
go back to reference Zhao X-Q, Morse JS, Dowdy AA, et al. Safety and tolerability of simvastatin plus niacin in patients with coronary artery disease and low high-density lipoprotein cholesterol (the HDL Atherosclerosis Treatment Study). Am J Cardiol 2004; 93: 307–12PubMedCrossRef Zhao X-Q, Morse JS, Dowdy AA, et al. Safety and tolerability of simvastatin plus niacin in patients with coronary artery disease and low high-density lipoprotein cholesterol (the HDL Atherosclerosis Treatment Study). Am J Cardiol 2004; 93: 307–12PubMedCrossRef
134.
go back to reference Kashyap ML, McGovern ME, Berra K, et al. Long-term safety and efficacy of a once-daily niacin/lovastatin formulation for patients with dyslipidemia. Am J Cardiol 2002; 89: 672–8PubMedCrossRef Kashyap ML, McGovern ME, Berra K, et al. Long-term safety and efficacy of a once-daily niacin/lovastatin formulation for patients with dyslipidemia. Am J Cardiol 2002; 89: 672–8PubMedCrossRef
135.
go back to reference Jacobson TA, Amorosa LF. Combination therapy with fluvastatin and niacin in hypercholesterolemia: a preliminary report on safety. Am J Cardiol 1994; 73: 25D–9DPubMedCrossRef Jacobson TA, Amorosa LF. Combination therapy with fluvastatin and niacin in hypercholesterolemia: a preliminary report on safety. Am J Cardiol 1994; 73: 25D–9DPubMedCrossRef
136.
go back to reference Pasternak RC, Brown LE, Stone PH, et al. for the Harvard Atherosclerosis Reversibility Project (HARP) Study Group. Effect of combination therapy with lipid-reducing drugs in patients with coronary heart disease and “normal” cholesterol levels: a randomized, placebo-controlled trial. Ann Intern Med 1996; 125: 529–40PubMed Pasternak RC, Brown LE, Stone PH, et al. for the Harvard Atherosclerosis Reversibility Project (HARP) Study Group. Effect of combination therapy with lipid-reducing drugs in patients with coronary heart disease and “normal” cholesterol levels: a randomized, placebo-controlled trial. Ann Intern Med 1996; 125: 529–40PubMed
Metadata
Title
Overcoming ‘Ageism’ Bias in the Treatment of Hypercholesterolaemia
A Review of Safety Issues with Statins in the Elderly
Author
Dr Terry A. Jacobson
Publication date
01-05-2006
Publisher
Springer International Publishing
Published in
Drug Safety / Issue 5/2006
Print ISSN: 0114-5916
Electronic ISSN: 1179-1942
DOI
https://doi.org/10.2165/00002018-200629050-00005

Other articles of this Issue 5/2006

Drug Safety 5/2006 Go to the issue