The American Journal of Medicine
Volume 121, Issue 1 , Pages 24-33 , January 2008

Statin Therapy in Stroke Prevention: A Meta-analysis Involving 121,000 Patients

  • Christopher O’Regan, MSc

      Affiliations

    • Department of Epidemiology, London School of Hygiene and Tropical Medicine, London, UK
    • ,
  • Ping Wu, MBBS, MSc

      Affiliations

    • Department of Epidemiology, London School of Hygiene and Tropical Medicine, London, UK
    • ,
  • Paul Arora, MSc

      Affiliations

    • Centre for Global Health Research, University of Toronto, Ontario, Canada
    • ,
  • Dan Perri, BScPhm, MD

      Affiliations

    • Department of Medicine, McMaster University, Hamilton, Ontario, Canada
    • ,
  • Edward J. Mills, MSc, PhD

      Affiliations

    • Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada.
    • Dr. Mills is supported by the Canadian Institutes of Health Research.
    • Corresponding Author InformationRequests for reprints should be addressed to Edward J. Mills, MSc, PhD, Department of Clinical Epidemiology and Biostatistics McMaster University, 1200 Main Street West, Rm. 2C12, Hamilton, Ontario L8N 3Z5, Canada.

References 

  1. American Heart Association. Heart Disease and Stroke Statistics—2006 Update. Dallas, TX: American Heart Association; 2006;
  2. Cholesterol, diastolic blood pressure, and stroke: 13,000 strokes in 450,000 people in 45 prospective cohorts (Prospective studies collaboration). Lancet. 1995;346:1647–1653
  3. Iso H, Jacobs DR, Wentworth D, et al. Serum cholesterol levels and six-year mortality from stroke in 350,977 men screened for the multiple risk factor intervention trial. N Engl J Med. 1989;320:904–910
  4. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet. 1994;344:1383–1389
  5. 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;335:1001–1009
  6. White HD, Simes RJ, Anderson NE, et al. Pravastatin therapy and the risk of stroke. N Engl J Med. 2000;343:317–326
  7. Heart Protection Study Collaborative Group. Mrc/bhf heart protection study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet. 2002;360:7–22
  8. 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;285:1711–1718
  9. 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;361:1149–1158
  10. Collins R, Armitage J, Parish S, et al. Effects of cholesterol-lowering with simvastatin on stroke and other major vascular events in 20,536 people with cerebrovascular disease or other high-risk conditions. Lancet. 2004;363:757–767
  11. Bucher HC, Griffith LE, Guyatt GH. Effect of hmgcoa reductase inhibitors on stroke (A meta-analysis of randomized, controlled trials). Ann Intern Med. 1998;128:89–95
  12. Hebert PR, Gaziano JM, Chan KS, Hennekens CH. Cholesterol lowering with statin drugs, risk of stroke, and total mortality (An overview of randomized trials). JAMA. 1997;278:313–321
  13. Blauw GJ, Lagaay AM, Smelt AH, Westendorp RG. Stroke, statins, and cholesterol (A meta-analysis of randomized, placebo-controlled, double-blind trials with hmg-coa reductase inhibitors). Stroke. 1997;28:946–950
  14. Briel M, Studer M, Glass TR, Bucher HC. Effects of statins on stroke prevention in patients with and without coronary heart disease: a meta-analysis of randomized controlled trials. Am J Med. 2004;117:596–606
  15. Vaughan CJ, Gotto AM, Basson CT. The evolving role of statins in the management of atherosclerosis. J Am Coll Cardiol. 2000;35:1–10
  16. Briel M, Nordmann AJ, Bucher HC. Statin therapy for prevention and treatment of acute and chronic cardiovascular disease: update on recent trials and meta-analyses. Curr Opin Lipidol. 2005;16:601–605
  17. Bucher HC, Griffith LE, Guyatt GH. Systematic review on the risk and benefit of different cholesterol-lowering interventions. Arterioscler Thromb Vasc Biol. 1999;19:187–195
  18. Studer M, Briel M, Leimenstoll B, et al. Effect of different antilipidemic agents and diets on mortality: a systematic review. Arch Intern Med. 2005;165:725–730
  19. Zhou Z, Rahme E, Pilote L. Are statins created equal? (Evidence from randomized trials of pravastatin, simvastatin, and atorvastatin for cardiovascular disease prevention). Am Heart J. 2006;151:273–281
  20. Baigent C, Keech A, Kearney PM, et al. Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins. Lancet. 2005;366:1267–1278
  21. NICE. Assessment report: coronary heart disease—statins. Available at: http://www.Nice.Org.Uk/pdf/statins_assessment_report.Pdf 2005. Accessed November 13, 2007.
  22. Meade MO, Guyatt GH, Cook RJ, et al. Agreement between alternative classifications of acute respiratory distress syndrome. Am J Respir Crit Care Med. 2001;163:490–493
  23. Sheehe PR. Combination of log relative risk in retrospective studies of disease. Am J Public Health Nations Health. 1966;56:1745–1750
  24. Fleiss JL. The statistical basis of meta-analysis. Stat Methods Med Res. 1993;2:121–145
  25. DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7:177–188
  26. Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med. 2002;21:1539–1558
  27. Thompson SG, Higgins JP. How should meta-regression analyses be undertaken and interpreted?. Stat Med. 2002;21:1559–1573
  28. 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;72:1031–1037
  29. Effect of simvastatin on coronary atheroma: the Multicentre Anti-Atheroma Study (MAAS). Lancet. 1994;344:633–638
  30. 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;339:1349–1357
  31. Results of the low-dose (20 mg) pravastatin gissi prevenzione trial in 4271 patients with recent myocardial infarction: do stopped trials contribute to overall knowledge? (Gissi prevenzione investigators (Gruppo Italiano per lo studio della sopravvivenza nell’infarto miocardico- GISSI)). Ital Heart J. 2000;1:810–820
  32. Major outcomes in moderately hypercholesterolemic, hypertensive patients randomized to pravastatin vs usual care: the antihypertensive and lipid-lowering treatment to prevent heart attack trial (ALLHAT-LLT). JAMA. 2002;288:2998–3007
  33. Adams HP. Effect of cholesterol-lowering medications on progression of mild atherosclerotic lesions of the carotid arteries and on the risk of stroke. Cerebrovasc Dis. 1995;5:171–177
  34. Amarenco P, Bogousslavsky J, Callahan A, et al. High-dose atorvastatin after stroke or transient ischemic attack. N Engl J Med. 2006;355:549–559
  35. Asselbergs FW, Diercks GF, Hillege HL, et al. Effects of fosinopril and pravastatin on cardiovascular events in subjects with microalbuminuria. Circulation. 2004;110:2809–2816
  36. 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 Coronary-heart-disease Evaluation (GREACE) study). Curr Med Res Opin. 2002;18:220–228
  37. Bestehorn HP, Rensing UF, Roskamm H, et al. The effect of simvastatin on progression of coronary artery disease (The multicenter coronary intervention study (CIS)). Eur Heart J. 1997;18:226–234
  38. Blankenhorn DH, Azen SP, Kramsch DM, et al. Coronary angiographic changes with lovastatin therapy (The monitored atherosclerosis regression study (MARS)). Ann Intern Med. 1993;119:969–976
  39. 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;364:685–696
  40. Crouse JR, Byington RP, Bond MG, et al. Pravastatin, lipids, and atherosclerosis in the carotid arteries (PLAC-ii). Am J Cardiol. 1995;75:455–459
  41. 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;279:1615–1622
  42. Hedblad B, Wikstrand J, Janzon L, et al. Low-dose metoprolol cr/xl and fluvastatin slow progression of carotid intima-media thickness: Main results from the beta-blocker cholesterol-lowering asymptomatic plaque study (BCAPS). Circulation. 2001;103:721–1726
  43. 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;361:2024–2031
  44. Jukema JW, Bruschke AV, van Boven AJ, et al. Effects of lipid lowering by pravastatin on progression and regression of coronary artery disease in symptomatic men with normal to moderately elevated serum cholesterol levels (The regression growth evaluation statin study (REGRESS)). Circulation. 1995;91:2528–2540
  45. Koren MJ, Hunninghake DB. Clinical outcomes in managed-care patients with coronary heart disease treated aggressively in lipid-lowering disease management clinics: the Alliance study. J Am Coll Cardiol. 2004;44:1772–1779
  46. Liem AH, van Boven AJ, Veeger NJ, et al. Effect of fluvastatin on ischaemia following acute myocardial infarction: a randomized trial. Eur Heart J. 2002;23:1931–1937
  47. Makuuchi H, Furuse A, Endo M, et al. Effect of pravastatin on progression of coronary atherosclerosis in patients after coronary artery bypass surgery. Circ J. 2005;69:636–643
  48. Mercuri M, Bond MG, Sirtori CR, et al. Pravastatin reduces carotid intima-media thickness progression in an asymptomatic hypercholesterolemic mediterranean population: the Carotid Atherosclerosis Italian Ultrasound Study. Am J Med. 1996;101:627–634
  49. Mohler ER, Hiatt WR, Creager MA. Cholesterol reduction with atorvastatin improves walking distance in patients with peripheral arterial disease. Circulation. 2003;108:1481–1486
  50. Nakagawa T, Kobayashi T, Awata N, et al. Randomized, controlled trial of secondary prevention of coronary sclerosis in normocholesterolemic patients using pravastatin: final 5-year angiographic follow-up of the prevention of coronary sclerosis (PCS) study. Int J Cardiol. 2004;97:107–114
  51. Nakamura H, Arakawa K, Itakura H, et al. Primary prevention of cardiovascular disease with pravastatin in Japan (MEGA study): a prospective randomised controlled trial. Lancet. 2006;368:1155–1163
  52. O’Rourke B, Barbir M, Mitchell AG, et al. Efficacy and safety of fluvastatin therapy for hypercholesterolemia after heart transplantation: results of a randomised double blind placebo controlled study. Int J Cardiol. 2004;94:235–240
  53. Petronio AS, Amoroso G, Limbruno U, et al. Simvastatin does not inhibit intimal hyperplasia and restenosis but promotes plaque regression in normocholesterolemic patients undergoing coronary stenting: a randomized study with intravascular ultrasound. Am Heart J. 2005;149:520–526
  54. Salonen R, Nyyssonen K, Porkkala E, et al. Kuopio Atherosclerosis Prevention Study (KAPS) (A population-based primary preventive trial of the effect of LDL lowering on atherosclerotic progression in carotid and femoral arteries). Circulation. 1995;92:1758–1764
  55. 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;287:3215–3222
  56. Shepherd J, Blauw GJ, Murphy MB, et al. Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial. Lancet. 2002;360:1623–1630
  57. 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;333:1301–1307
  58. Stone PH, Lloyd-Jones DM, Kinlay S, et al. Effect of intensive lipid lowering, with or without antioxidant vitamins, compared with moderate lipid lowering on myocardial ischemia in patients with stable coronary artery disease: the vascular basis for the treatment of myocardial ischemia study. Circulation. 2005;111:1747–1755
  59. Teo KK, Burton JR, Buller CE, et al. Long-term effects of cholesterol lowering and angiotensin-converting enzyme inhibition on coronary atherosclerosis: the simvastatin/enalapril coronary atherosclerosis trial (SCAT). Circulation. 2000;102:1748–1754
  60. Wanner C, Krane V, Marz W, et al. Atorvastatin in patients with type 2 diabetes mellitus undergoing hemodialysis. N Engl J Med. 2005;353:238–248
  61. Waters D, Higginson L, Gladstone P, et al. Effects of monotherapy with an hmg-coa reductase inhibitor on the progression of coronary atherosclerosis as assessed by serial quantitative arteriography (The Canadian Coronary Atherosclerosis Intervention Trial). Circulation. 1994;89:959–968
  62. Yokoi H, Nobuyoshi M, Mitsudo K, et al. Three-year follow-up results of angiographic intervention trial using an hmg-coa reductase inhibitor to evaluate retardation of obstructive multiple atheroma (ATHEROMA) study. Circ J. 2005;69:875–883
  63. Zanchetti A, Crepaldi G, Bond MG, et al. Different effects of antihypertensive regimens based on fosinopril or hydrochlorothiazide with or without lipid lowering by pravastatin on progression of asymptomatic carotid atherosclerosis: principal results of PHYLLIS—a randomized double-blind trial. Stroke. 2004;35:2807–2812
  64. Sakamoto T, Kojima S, Ogawa H, et al. Effects of early statin treatment on symptomatic heart failure and ischemic events after acute myocardial infarction in Japanese. Am J Cardiol. 2006;97:1165–1171
  65. Iwashita M, Matsushita Y, Sasaki J, et al. Relation of serum total cholesterol and other factors to risk of cerebral infarction in Japanese men with hypercholesterolemia. Circ J. 2005;69:1–6
  66. Goldstein LB, Amarenco P, Bogousslavsky J, et al. Statins for secondary stroke prevention in patients without known coronary heart disease: the jury is still out. Cerebrovasc Dis. 2004;18:1–2
  67. Song F, Altman DG, Glenny AM, Deeks JJ. Validity of indirect comparison for estimating efficacy of competing interventions: Empirical evidence from published meta-analyses. BMJ. 2003;326:472
  68. Silva MA, Swanson AC, Gandhi PJ, Tataronis GR. Statin-related adverse events: a meta-analysis. Clin Ther. 2006;28:26–35
  69. Trubelja N, Vaughan C, Coplan NL. The role of statins in preventing stroke. Prev Cardiol. 2005;8:98–101

PII: S0002-9343(07)00977-1

doi: 10.1016/j.amjmed.2007.06.033

The American Journal of Medicine
Volume 121, Issue 1 , Pages 24-33 , January 2008

Article Tools

* Image Usage & Resolution