Current Atherosclerosis Reports

, Volume 11, Issue 4, pp 315–321 | Cite as

Review of the SPARCL trial and its subanalyses

Article

Abstract

The Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) study is a prospective, randomized, placebo-controlled trial that was designed to determine whether 80 mg/d of atorvastatin reduced the risk of fatal or nonfatal stroke in patients who had previously experienced a stroke or transient ischemic attack. It is unique in that it is the only trial to study this cohort of patients with no known coronary heart disease. The review recaps the results of the primary SPARCL data and discusses the findings of subsequent analyses that extend the conclusions from the study. Atorvastatin reduced the risk of stroke to a clinically persuasive degree. This benefit was present despite a small increase in risk of intracerebral hemorrhage. Factors were identified in SPARCL that might reduce this risk if implemented. Further subanalyses addressed other questions relative to stroke profile of benefit and potential mechanisms of statin action. SPARCL has established that statins have an important role in secondary stroke prevention.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References and Recommended Reading

  1. 1.
    Sacco RL, Adams R, Albers G, et al.: Guidelines for prevention of stroke in patients with ischemic stroke or transient ischemic attack: a statement for healthcare professionals from the American Heart Association/American Stroke Association Council on Stroke: co-sponsored by the Council on Cardiovascular Radiology and Intervention: the American Academy of Neurology affirms the value of this guideline. Stroke 2006, 37:577–617.PubMedCrossRefGoogle Scholar
  2. 2.
    Scandinavian Simvastatin Survival Study Group: Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet 1994, 344:1383–1389.Google Scholar
  3. 3.
    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, 339:1349–1357.CrossRefGoogle Scholar
  4. 4.
    Plehn JF, Davis BR, Sacks FM, et al.: Reduction of stroke incidence after myocardial infarction with pravastatin. The Cholesterol and Recurrent Events (CARE) study. Circulation 1999, 99:216–223.PubMedGoogle Scholar
  5. 5.
    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.PubMedCrossRefGoogle Scholar
  6. 6.
    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 placebocontrolled trial. Lancet 2004, 364:685–696.PubMedCrossRefGoogle Scholar
  7. 7.
    Heart Protection Collaborative Study 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.CrossRefGoogle Scholar
  8. 8.
    Amarenco P, Labreuche J, Lavallée P, Touboul PJ: Statin in stroke prevention and carotid atherosclerosis: systematic review and meta-analysis. Stroke 2004, 35:2902–2909.PubMedCrossRefGoogle Scholar
  9. 9.
    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.PubMedCrossRefGoogle Scholar
  10. 10.
    Heart Protection Collaborative Study Group: 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.CrossRefGoogle Scholar
  11. 11.
    The Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) Investigators: High-dose atorvastatin after stroke or transient ischemic attack. N Engl J Med 2006, 355:549–559CrossRefGoogle Scholar
  12. 12.
    Amarenco P, Lavallée PC, Touboul PJ: Stroke prevention, blood cholesterol and statins. Lancet Neurol 2004, 3:271–278.PubMedCrossRefGoogle Scholar
  13. 13.
    Vickrey BG, Rector TS, Wickstrom SL, et al.: Occurrence of secondary ischemic events among persons with atherosclerotic vascular disease. Stroke 2002, 33:901–906.PubMedCrossRefGoogle Scholar
  14. 14.
    Hardie K, Hankey GJ, Jamrozik K, et al.: Ten-year risk of first recurrent stroke and disability after first-ever stroke in the Perth Community Stroke Study. Stroke 2004, 35:731–735.PubMedCrossRefGoogle Scholar
  15. 15.
    Iso H, Jacobs DR, Wentworth D, et al., for the MRFIT Research Group: 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.PubMedGoogle Scholar
  16. 16.
    Yano K, Reed DM, McLean CJ: Serum cholesterol and hemorrhagic stroke in the Honolulu Heart Program. Stroke 1989, 20:1460–1465.PubMedGoogle Scholar
  17. 17.
    Wiviott SD, Cannon CP, Morrow DA, et al.: Can low-density lipoprotein be too low? The safety and efficacy of achieving very low low-density lipoprotein with intensive statin therapy: a PROVE IT-TIMI 22 substudy. J Am Coll Cardiol 2005, 46:1411–1416.PubMedCrossRefGoogle Scholar
  18. 18.
    Waters DD, LaRosa JC, Barter P, et al.: Effects of intensive lipid lowering with atorvastatin on cerebrovascular events in patients with stable coronary disease: a Treating to New Targets (TNT) substudy [abstract 2019]. Circulation 2005, 112(17 Suppl 1):2020.Google Scholar
  19. 19.
    Bushnell CD, Hurn P, Colton C, et al.: Advancing the study of stroke in women. Summary and recommendations for future research from an NINDS-sponsored multidisciplinary working group. Stroke 2006, 37:2387–2399.PubMedCrossRefGoogle Scholar
  20. 20.
    Bushnell CD, Griffin J, Newby LK, et al.: Statin use and sex-specific stroke outcomes in patients with vascular disease. Stroke 2006, 37:1427–1431.PubMedCrossRefGoogle Scholar
  21. 21.
    Goldstein LB, Amerenco P, LaMonte M, et al.: Relative effects of statin therapy on stroke and cardiovascular events in men and women: secondary analysis of the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) study. Stroke 2008, 39:2444–2448.PubMedCrossRefGoogle Scholar
  22. 22.
    He W, Sengupta M, Velkoff VA, DeBarros KA: US Census Bureau, Current Population Reports, 65+ in the United States: 2005. Washington, DC: US Government Printing Office; 2005:23–29.Google Scholar
  23. 23.
    Robinson JG, Bakris G, Torner J, et al.: Is it time for a cardiovascular primary prevention trial in the elderly? Stroke 2007, 38:441–450.PubMedCrossRefGoogle Scholar
  24. 24.
    Olsson AG, Schwartz G, Szarek M, et al.: Effects of high-dose atorvastatin in patients >65 years of age with acute coronary syndrome (from the Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) study). Am J Cardiol 2007, 99:632–635.PubMedCrossRefGoogle Scholar
  25. 25.
    Cholesterol Treatment Trialists’ (CTT) Collaborators: 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.CrossRefGoogle Scholar
  26. 26.
    Chaturvedi S, Zivin J, Breazna A, et al.: Effect of atorvastatin in elderly patients with a recent stroke or transient ischemic attack. Neurology 2009, 72:688–694.PubMedCrossRefGoogle Scholar
  27. 27.
    Ko DT, Mamdani M, Alter DA: Lipid-lowering therapy with statins in high-risk elderly patients: The treatment-risk paradox. JAMA 2004, 291:1864–1870.PubMedCrossRefGoogle Scholar
  28. 28.
    Grundy SM, Cleeman JI, Merz CN, et al., for the Coordinating Committee of the National Cholesterol Education Program, Endorsed by the National Heart L, and Blood Institute, American College of Cardiology Foundation, and American Heart Association: Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation 2004, 110:227–239.PubMedCrossRefGoogle Scholar
  29. 29.
    Petty GW, Brown RD Jr, Whisnant JP, et al.: Ischemic stroke subtypes: a population-based study of functional outcome, survival, and recurrence. Stroke 2000, 31:1062–1068.PubMedGoogle Scholar
  30. 30.
    Albers GW, Amarenco P, Easton JD, et al.: Antithrombotic and thrombolytic therapy for ischemic stroke: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 2004, 126(3 Suppl):483S–512S.PubMedCrossRefGoogle Scholar
  31. 31.
    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.PubMedCrossRefGoogle Scholar
  32. 32.
    Sacco RL, Benjamin EJ, Broderick JP, et al.: American Heart Association Prevention Conference. IV. Prevention and Rehabilitation of Stroke. Risk factors. Stroke 1997, 28:1507–1517.PubMedGoogle Scholar
  33. 33.
    Amarenco P, Benavente MD, Goldstein LB, et al.: Results of the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial by stroke subtypes. Stroke 2009, 40:1405–1409.PubMedCrossRefGoogle Scholar
  34. 34.
    Gongora-Rivera F, Labreuche J, Jaramillo A, et al.: Autopsy prevalence of coronary atherosclerosis in patients with fatal stroke. Stroke 2007, 38:1203–1210.PubMedCrossRefGoogle Scholar
  35. 35.
    Goldstein LB, Amarenco P, Szarek M, et al.: Secondary analysis of hemorrhagic stroke in the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) Study. Neurology 2008, 70:2364–2370.PubMedCrossRefGoogle Scholar
  36. 36.
    Hennerici O, Huelsboemer HB, Hefter H, et al.: Natural history of asymptomatic extracranial disease. Results of a long-term prospective study. Brain 1987, 110:777–791.PubMedCrossRefGoogle Scholar
  37. 37.
    Hankey GJ, Jamrozik K, Broadhurst RJ, et al.: Five-year survival after first-ever stroke and related prognostic factors in the Perth Community Stroke Study. Stroke 2000, 31:2080–2086.PubMedGoogle Scholar
  38. 38.
    Sillesen H, Amerenco P, Hennerici M, et al.: Atorvastatin reduces the risk of cardiovascular events in patients with carotid atherosclerosis: a secondary analysis of hemorrhagic stroke in the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial. Stroke 2008, 39:3297–3302.PubMedCrossRefGoogle Scholar
  39. 39.
    Executive Committee for the Asymptomatic Carotid Atherosclerosis Study: End-arterectomy for asymptomatic carotid stenosis. JAMA 1995, 273:1421–1428.CrossRefGoogle Scholar
  40. 40.
    MRC Asymptomatic Carotid Surgery Trial (ACST) Collaborative Group: Prevention of disabling and fatal strokes by successful carotid endarterectomy in patients without recent neurological symptoms: randomised controlled trial. Lancet 2004, 363:1491–502.CrossRefGoogle Scholar
  41. 41.
    Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults: Executive summary of the 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). JAMA 2001, 285:2486–2497.CrossRefGoogle Scholar
  42. 42.
    Jackson C, Sudlow C: Comparing risks of death and recurrent vascular events between lacunar and non-lacunar infarction. Brain 2005, 128:2507–2517.PubMedCrossRefGoogle Scholar
  43. 43.
    Prospective Studies Collaboration: Cholesterol, diastolic blood pressure, and stroke: 13,000 strokes in 450,000 people in 45 prospective cohorts. Lancet 1995, 346:1647–1653.CrossRefGoogle Scholar
  44. 44.
    Amarenco P, Goldstein LB, Callahan A, et al.: Baseline blood pressure, low-and high-density lipoproteins, and triglycerides and the risk of vascular events in the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial. Atherosclerosis 2008 Sep 18 [Epub ahead of print].Google Scholar
  45. 45.
    Patel A, Woodward M, Campbell DJ, et al.: Plasma lipids predict myocardial infarction, but not stroke, in patients with established cerebrovascular disease. Eur Heart J 2005, 26:1910–1915.PubMedCrossRefGoogle Scholar
  46. 46.
    Amarenco P, Goldstein LB, Szarek M, et al.: Effects of intense low-density lipoprotein cholesterol reduction in patients with stroke or transient ischemic attack. Stroke 2007, 38:3198–3204.PubMedCrossRefGoogle Scholar
  47. 47.
    Delanty N, Vaughan CJ: Vascular effects of statins in stroke. Stroke 1997, 28:2315–2320.PubMedGoogle Scholar
  48. 48.
    Takemoto M, Liao JK: Pleiotropic effects of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors. Arterioscler Thromb Vasc Biol 2001, 21:1712–1719.PubMedCrossRefGoogle Scholar
  49. 49.
    Amarenco P, Goldstein LB, Messig M, et al.: Relative and cumulative effects of lipid and blood pressure control in the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial. Stroke 2009 (in press).Google Scholar
  50. 50.
    Gaede P, Vedel P, Larsen N, et al.: Multifactorial intervention and cardiovascular disease in patients with type 2 diabetes. N Engl J Med 2003, 348:383–393.PubMedCrossRefGoogle Scholar
  51. 51.
    Gaede P, Lund-Andersen H, Parving HH, Pedersen O: Effect of a multifactorial intervention on mortality in type 2 diabetes. N Engl J Med 2008, 358:580–591.PubMedCrossRefGoogle Scholar
  52. 52.
    Ariesen MJ, Claus SP, Rinkel GJ, Algra A: Risk factors for intracerebral hemorrhage in the general population: a systematic review. Stroke 2003, 34:2060–2065.PubMedCrossRefGoogle Scholar
  53. 53.
    Hill MD, Silver FL, Austin PC, Tu JV: Rate of stroke recurrence in patients with primary intracerebral hemorrhage. Stroke 2000, 31:123–127.PubMedGoogle Scholar
  54. 54.
    PROGRESS Collaborative Group: Randomised trial of a perindopril-based blood-pressure-lowering regimen among 6105 individuals with previous stroke or transient ischaemic attack. Lancet 2001, 358:1033–1041.CrossRefGoogle Scholar

Copyright information

© Current Medicine Group, LLC 2009

Authors and Affiliations

  1. 1.Rosalind Franklin University of Medicine & ScienceNorth ChicagoUSA

Personalised recommendations