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Drugs

, Volume 69, Issue 6, pp 633–647 | Cite as

Pharmacotherapy for the Secondary Prevention of Stroke

  • Kazunori ToyodaEmail author
Therapy in Practice

Abstract

Stroke recurrence continues to be the major risk for stroke survivors. Risk factor control and antithrombotic medication are two major strategies for patients with a prior stroke or transient ischaemic attack (TIA) to prevent stroke recurrence.

Hypertension, dyslipidaemia and diabetes mellitus are risk factors that are modifiable by pharmacotherapy, as well as by lifestyle modification. Antihypertensive treatment is recommended for secondary stroke prevention for both hypertensive and normotensive patients. HMG-CoA reductase inhibitor (statin) therapy to obtain an intensive lipid-lowering effect is also highly recommended. A recent trial indicated that treatment with pioglitazone is effective for patients with type 2 diabetes. However, the evidence for risk factor control is relatively new, and further studies are needed for better evidence-based prevention.

For patients with noncardioembolic ischaemic stroke or TIA, antiplatelet therapy rather than anticoagulation is recommended to reduce the risk of recurrent stroke and other cardiovascular events. Aspirin was the first antiplatelet agent to have established evidence for secondary stroke prevention. Currently, aspirin monotherapy, the combination of aspirin and extendedrelease dipyridamole, and clopidogrel monotherapy are recommended as the major choices. The combination of aspirin and clopidogrel is not routinely recommended. Adjusted-dose warfarin with a target international normalized ratio range between 2.0 and 3.0 is recommended after an ischaemic stroke or TIA associated with nonvalvular atrial fibrillation. Bleeding complications are a critical problem with antithrombotic therapy. Warfarin, as well as antiplatelet therapy, increases the incidence of bleeding and worsens the severity of the bleeding events. Choosing antithrombotic agents and their intensity (dosage) appropriate to the stroke mechanism and the patient’s condition are essential for secondary stroke prevention.

Keywords

International Normalize Ratio Antiplatelet Agent Cilostazol Recurrent Stroke Antithrombotic Therapy 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgements

This article was partially supported by a Grant-in-Aid (H20-Junkanki-Ippan-019) from the Ministry of Health, Labour and Welfare, Japan, and a Grant-in-Aid for Scientific Research (Kiban C, #20591039) from the Japan Society for the Promotion of Science. The author has no conflicts of interest that are directly relevant to the content of this review.

References

  1. 1.
    Rundek T, Sacco RL. Outcome following stroke. In: Mohr JP, Choi DW, Grotta JC, et al., editors. Stroke: pathophysiology, diagnosis, and management. 4th ed. Philadelphia (PA): Churchill Livingstone, 2004: 35–57Google Scholar
  2. 2.
    Dhamoon MS, Sciacca RR, Rundek T, et al. Recurrent stroke and cardiac risks after first ischemic stroke: the Northern Manhattan Study. Neurology 2006 Mar 14; 66(5): 641–6PubMedCrossRefGoogle Scholar
  3. 3.
    Johnston SC, Gress DR, Browner WS, et al. Short-term prognosis after emergency department diagnosis of TIA. JAMA 2000 Dec 13; 284(22): 2901–6PubMedCrossRefGoogle Scholar
  4. 4.
    Lovett JK, Dennis MS, Sandercock PA, et al. Very early risk of stroke after a first transient ischemic attack. Stroke 2003 Aug; 34(8): e138–40PubMedCrossRefGoogle Scholar
  5. 5.
    Coull AJ, Lovett JK, Rothwell PM, Oxford Vascular Study. Population based study of early risk of stroke after transient ischaemic attack or minor stroke: implications for public education and organisation of services. BMJ 2004 Feb 7; 328(7435): 326PubMedCrossRefGoogle Scholar
  6. 6.
    Hill MD, Yiannakoulias N, Jeerakathil T, et al. The high risk of stroke immediately after transient ischemic attack: a population-based study. Neurology 2004 Jun 8; 62(11): 2015–20PubMedCrossRefGoogle Scholar
  7. 7.
    Kleindorfer D, Panagos P, Pancioli A, et al. Incidence and short-term prognosis of transient ischemic attack in a population-based study. Stroke 2005 Apr; 36(4): 720–3PubMedCrossRefGoogle Scholar
  8. 8.
    Tsivgoulis G, Spengos K, Manta P, et al. Validation of the ABCD score in identifying individuals at high early risk of stroke after a transient ischemic attack: a hospital-based case series study. Stroke 2006 Dec; 37(12): 2892–7PubMedCrossRefGoogle Scholar
  9. 9.
    Correia M, Silva MR, Magalhães R, et al. Transient ischemic attacks in rural and urban northern Portugal: incidence and short-term prognosis. Stroke 2006 Jan; 37(1): 50–5PubMedCrossRefGoogle Scholar
  10. 10.
    Toyoda K, Okada Y, Kobayashi S, for the Japan Standard Stroke Registry Study group. Early recurrence of ischemic stroke in Japanese patients: the Japan Standard Stroke Registry Study. Cerebrovasc Dis 2007; 24(2–3): 289–95PubMedCrossRefGoogle Scholar
  11. 11.
    Lavallée PC, Meseguer E, Abboud H, et al. A transient ischaemic attack clinic with round-the-clock access (SOS-TIA): feasibility and effects. Lancet Neurol 2007 Nov; 6(11): 953–60PubMedCrossRefGoogle Scholar
  12. 12.
    Rothwell PM, Giles MF, Chandratheva A, et al. Effect of urgent treatment of transient ischaemic attack and minor stroke on early recurrent stroke (EXPRESS study): a prospective population-based sequential comparison. Lancet 2007 Oct 20; 370(9596): 1432–42PubMedCrossRefGoogle Scholar
  13. 13.
    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 Feb; 37(2): 577–617Google Scholar
  14. 14.
    Adams RJ, Albers G, Alberts MJ, et al. Update to the AHA/ASA recommendations for the prevention of stroke in patients with stroke and transient ischemic attack. Stroke 2008 May; 39(5): 1647–52PubMedCrossRefGoogle Scholar
  15. 15.
    European Stroke Organisation (ESO) Executive Committee and the ESO Writing Committee. Guidelines for management of ischaemic stroke and transient ischaemic attack 2008. Cerebrovasc Dis 2008 May; 25(5): 457–507CrossRefGoogle Scholar
  16. 16.
    Albers GW, Amarenco P, Easton JD, et al. Antithrombotic and thrombolytic therapy for ischemic stroke: American College of Chest Physicians evidence-based clinical practice guidelines. 8th ed. Chest 2008 Jun; 133 (6 Suppl.): 630–69SCrossRefGoogle Scholar
  17. 17.
    Shinohara Y, Yamaguchi T. Outline of the Japanese guidelines for the management of stroke 2004 and subsequent revision. Int J Stroke 2008 Feb; 3(1): 55–62PubMedCrossRefGoogle Scholar
  18. 18.
    Turnbull F, Blood Pressure Lowering Treatment Trialists’ Collaboration. Effects of different blood-pressure-lowering regimens on major cardiovascular events: results of prospectively-designed overviews of randomised trials. Lancet 2003 Nov 8; 362(9395): 1527–35PubMedCrossRefGoogle Scholar
  19. 19.
    Amarenco P, Labreuche J, Lavallee P, et al. Statins in stroke prevention and carotid atherosclerosis: systemic review and up-to-date meta-analysis. Stroke 2004 Dec; 35(12): 2902–9PubMedCrossRefGoogle Scholar
  20. 20.
    Goldstein LB, Adams R, Alberts MJ, et al. Primary prevention of ischemic stroke: a guideline from the American Heart Association/American Stroke Association Stroke Council. Co-sponsored by the Atherosclerotic Peripheral Vascular Disease Interdisciplinary Working Group; Cardiovascular Nursing Council; Clinical Cardiology Council; Nutrition, Physical Activity, and Metabolism Council; and the Quality of Care and Outcomes Research Interdisciplinary Working Group: the American Academy of Neurology affirms the value of this guideline. Stroke 2006 Jun; 37(6): 1583–633Google Scholar
  21. 21.
    PROGRESS Collaborative Group. Randomised trial of a perindopril-based blood-pressure-lowering regimen among 6,105 individuals with previous stroke or transient ischaeic attack. Lancet 2001 Sep 29; 358(9287): 1033–41CrossRefGoogle Scholar
  22. 22.
    Amarenco P, Bogousslavsky J, Callahan 3rd A, et al. Highdose atorvastatin after stroke or transient ischemic attack. N Engl J Med 2006 Aug 10; 355(6): 549–59PubMedCrossRefGoogle Scholar
  23. 23.
    Wilcox R, Bousser MG, Betteridge DJ, et al. Effects of pioglitazone in patients with type 2 diabetes with or without previous stroke: results from PROactive (PROspective pioglitAzone Clinical Trial In macroVascularEvents 04). Stroke 2007 Mar; 38(3): 865–73PubMedCrossRefGoogle Scholar
  24. 24.
    Tzourio C, Anderson C, Chapman N, et al. Effects of blood pressure lowering with perindopril and indapamide therapy on dementia and cognitive decline in patients with cerebrovascular disease. Arch Intern Med 2003 May 12; 163(9): 1069–75PubMedCrossRefGoogle Scholar
  25. 25.
    Fransen M, Anderson C, Chalmers J, et al. Effects of a perindopril-based blood pressure-lowering regimen on disability and dependency in 6105 patients with cerebrovascular disease: a randomized controlled trial. Stroke 2003 Oct; 34(10): 2333–8PubMedCrossRefGoogle Scholar
  26. 26.
    Rashid P, Leonardi-Bee J, Bath P. Blood pressure reduction and secondary prevention of stroke and other vascular events: a systematic review. Stroke 2003 Nov; 34(11): 2741–8PubMedCrossRefGoogle Scholar
  27. 27.
    Arima H, Chalmers J, Woodward M, et al. Lower target blood pressures are safe and effective for the prevention of recurrent stroke: the PROGRESS trial. J Hypertens 2006 Jun; 24(6): 1201–8PubMedCrossRefGoogle Scholar
  28. 28.
    Mancia G, De Backer G, Dominiczak A, et al. 2007 Guidelines for the management of arterial hypertension: the task force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J Hypertens 2007 Jun; 25(6): 1105–87PubMedCrossRefGoogle Scholar
  29. 29.
    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 May 21; 289(19): 2560–72PubMedCrossRefGoogle Scholar
  30. 30.
    Schrader J, Luders S, Kulschewski A, et al. Morbidity and mortality after stroke: eprosartan compared with nitrendipine for secondary prevention: principal results of a prospective randomized controlled study (MOSES). Stroke 2005 Jun; 36(6): 1218–26PubMedCrossRefGoogle Scholar
  31. 31.
    Yusuf S, Diener HC, Sacco RL, et al. Telmisartan to prevent recurrent stroke and cardiovascular events. N Engl J Med 2008 Sep 18; 359(12): 1225–37PubMedCrossRefGoogle Scholar
  32. 32.
    Collins R, Armitage J, Parish S, et al. Effects of cholesterollowering with simvastatin on stroke and other major vascular events in 20536 people with cerebrovascular disease or other high-risk conditions. Lancet 2004 Mar 6; 363(9411): 757–67PubMedCrossRefGoogle Scholar
  33. 33.
    Goldstein LB, Amarenco P, Szarek M, et al. Hemorrhagic stroke in the Stroke Prevention by Aggressive Reduction in Cholesterol Levels study. Neurology 2008 Jun 10; 70 (24 Pt 2): 2364–70PubMedCrossRefGoogle Scholar
  34. 34.
    Vergouwen MD, de Haan RJ, Vermeulen M, et al. Statin treatment and the occurrence of hemorrhagic stroke in patients with a history of cerebrovascular disease. Stroke 2008 Feb; 39(2): 497–502PubMedCrossRefGoogle Scholar
  35. 35.
    UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet 1998 Sep 12; 352(9131): 837–53CrossRefGoogle Scholar
  36. 36.
    ADVANCE Collaborative Group. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med 2008 Jun 12; 358(24): 2560–72CrossRefGoogle Scholar
  37. 37.
    Antithrombotic Trialists’ Collaboration. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ 2002 Jan 12; 324(7329): 71–86CrossRefGoogle Scholar
  38. 38.
    Yasaka M, Yamaguchi T. Secondary prevention of stroke in patients with nonvalvular atrial fibrillation: optimal intensity of anticoagulation. CNS Drugs 2001; 15(8): 623–31PubMedCrossRefGoogle Scholar
  39. 39.
    O’Donnell MJ, Hankey GJ, Eikelboom JW. Antiplatelet therapy for secondary prevention of noncardioembolic ischemic stroke: a critical review. Stroke 2008 May; 39(5): 1638–46PubMedCrossRefGoogle Scholar
  40. 40.
    Diener HC, Cunha L, Forbes C, et al. European Stroke Prevention Study: 2, dipyridamole and acetylsalicylic acid in the secondary prevention of stroke. J Neurol Sci 1996 Nov; 143(1–2): 1–13PubMedCrossRefGoogle Scholar
  41. 41.
    ESPRIT Study Group. Aspirin plus dipyridamole versus aspirin alone after cerebral ischaemia of arterial origin (ESPRIT): randomised controlled trial. Lancet 2006 May 20; 367(9523): 1665–73CrossRefGoogle Scholar
  42. 42.
    CAPRIE Steering Committee. A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). Lancet 1996 Nov 16; 348(9038): 1329–39CrossRefGoogle Scholar
  43. 43.
    Sacco RL, Diener HC, Yusuf S, et al. Aspirin and extendedrelease dipyridamole versus clopidogrel for recurrent stroke. N Engl J Med 2008 Sep 18; 359(12): 1238–51PubMedCrossRefGoogle Scholar
  44. 44.
    Costa J, Ferro JM, Matias-Guiu J, et al. Triflusal for preventing serious vascular events in people at high risk. Cochrane Database Syst Rev 2005 Jul 20; (3): CD004296Google Scholar
  45. 45.
    Gotoh F, Tohgi H, Hirai S, et al. Cilostazol Stroke Prevention Study: a placebo-controlled double-blind trial for secondary prevention of cerebral infarction. J Stroke Cerebrovasc Dis 2000 Jul–Aug; 9(4): 147–57CrossRefGoogle Scholar
  46. 46.
    Huang Y, Cheng Y, Wu J, et al. Cilostazol as an alternative to aspirin after ischaemic stroke: a randomised, double-blind, pilot study. Lancet Neurol 2008 Jun; 7(6): 494–9PubMedCrossRefGoogle Scholar
  47. 47.
    Markus HS, Droste DW, Kaps M, et al. Dual antiplatelet therapy with clopidogrel and aspirin in symptomatic carotid stenosis evaluated using Doppler embolic signal detection: the Clopidogrel and Aspirin for Reduction of Emboli in Symptomatic Carotid Stenosis (CARESS) trial. Circulation 2005 May 3; 111(17): 2233–40PubMedCrossRefGoogle Scholar
  48. 48.
    Diener HC, Bogousslavsky J, Brass LM, et al. Aspirin and clopidogrel compared with clopidogrel alone after recent ischaemic stroke or transient ischaemic attack in high-risk patients (MATCH): randomised, double-blind, placebocontrolled trial. Lancet 2004 Jul 24–30; 364(9431): 331–7PubMedCrossRefGoogle Scholar
  49. 49.
    Bhatt DL, Fox KA, Hacke W, et al. Clopidogrel and aspirin versus aspirin alone for the prevention of atherothrombotic events. N Engl J Med 2006 Apr 20; 354(16): 1706–17PubMedCrossRefGoogle Scholar
  50. 50.
    Atrial Fibrillation Investigators. Risk factors for stroke and efficacy of antithrombotic therapy in atrial fibrillation: analysis of pooled data from five randomized controlled trials. Arch Intern Med 1994 Jul 11; 154(13): 1449–57CrossRefGoogle Scholar
  51. 51.
    Stroke Prevention in Atrial Fibrillation Investigators. Adjusteddose warfarin versus low-intensity, fixed-dose warfarin plus aspirin for high-risk patients with atrial fibrillation: Stroke Prevention in Atrial Fibrillation III randomised clinical trial. Lancet 1996 Sep 7; 348(9028): 633–8CrossRefGoogle Scholar
  52. 52.
    EAFT (European Atrial Fibrillation Trial) Study Group. Secondary prevention in non-rheumatic atrial fibrillation after transient ischaemic attack or minor stroke. Lancet 1993 Nov 20; 342(8882): 1255–62Google Scholar
  53. 53.
    Fuster V, Rydén LE, Cannom DS, et al. ACC/AHA/ESC 2006 Guidelines for the Management of Patients with Atrial Fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation) — developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society. Circulation 2006 Aug 15; 114(7): e257–354PubMedCrossRefGoogle Scholar
  54. 54.
    Yamaguchi T, for Japanese Nonvalvular Atrial Fibrillation-Embolism Secondary Prevention Cooperative Study Group. Optimal intensity of warfarin therapy for secondary prevention of stroke in patients with nonvalvular atrial fibrillation: a multicenter, prospective, randomized trial. Stroke 2000 Apr; 31(4): 817–21PubMedCrossRefGoogle Scholar
  55. 55.
    Yasaka M, Minematsu K, Yamaguchi T. Optimal intensity of international normalized ratio in warfarin therapy for secondary prevention of stroke in patients with non-valvular atrial fibrillation. Intern Med 2001 Dec; 40(12): 1183–8PubMedCrossRefGoogle Scholar
  56. 56.
    Shen AY, Chen W, Yao JF, et al. Effect of race/ethnicity on the efficacy of warfarin: potential implications for prevention of stroke in patients with atrial fibrillation. CNS Drugs 2008; 22(10): 815–25PubMedCrossRefGoogle Scholar
  57. 57.
    The Stroke Prevention in Reversible Ischemia Trial (SPIRIT) Study Group. A randomized trial of anticoagulants versus aspirin after cerebral ischemia of presumed arterial origin. Ann Neurol 1997 Dec; 42(6): 857–65CrossRefGoogle Scholar
  58. 58.
    Algra A, De Schryver EL, van Gijn J, et al. Oral anticoagulants versus antiplatelet therapy for preventing further vascular events after transient ischaemic attack or minor stroke of presumed arterial origin. Cochrane Database Syst Rev 2006 Jul 19; (3): CD001342Google Scholar
  59. 59.
    Hart RG, Tonarelli SB, Pearce LA. Avoiding central nervous system bleeding during antithrombotic therapy: recent data and ideas. Stroke 2005 Jul; 36(7): 1588–93PubMedCrossRefGoogle Scholar
  60. 60.
    Kase CS, Mohr JP, Caplan LR. Intracerebral hemorrhage. In: Mohr JP, Choi DW, Grotta JC, et al., editors. Stroke: pathophysiology, diagnosis, and management, 4th ed. Philadelphia (PA): Churchill Livingstone, 2004: 327–76Google Scholar
  61. 61.
    Kubo M, Kiyohara Y, Kato I, et al. Trends in the incidence, mortality, and survival rate of cardiovascular disease in a Japanese community: the Hisayama study. Stroke 2003 Oct; 34(10): 2349–54PubMedCrossRefGoogle Scholar
  62. 62.
    Tanaka H, Ueda Y, Date C, et al. Incidence of stroke in Shibata, Japan: 1976–1978. Stroke 1981 Jul–Aug; 12(4): 460–6PubMedCrossRefGoogle Scholar
  63. 63.
    Jiang B, Wang WZ, Chen H, et al. Incidence and trends of stroke and its subtypes in China: results from three large cities. Stroke 2006 Jan; 37(1): 63–8PubMedCrossRefGoogle Scholar
  64. 64.
    Bruno A, Carter S, Qualls C, et al. Incidence of spontaneous intracerebral hemorrhage among Hispanics and non-Hispanic whites in New Mexico. Neurology 1996 Aug; 47(2): 405–8PubMedCrossRefGoogle Scholar
  65. 65.
    Drury I, Whisnant JP, Garraway WM. Primary intracerebral hemorrhage: impact of CT on incidence. Neurology 1984 May; 34(5): 653–7PubMedCrossRefGoogle Scholar
  66. 66.
    Sacco RL, Wolf PA, Bharucha NE, et al. Subarachnoid and intracerebral hemorrhage: natural history, prognosis, and precursive factors in the Framingham Study. Neurology 1984 Jul; 34(7): 847–54PubMedCrossRefGoogle Scholar
  67. 67.
    Schütz H, Bödeker RH, Damian M, et al. Age-related spontaneous intracerebral hematoma in a German community. Stroke 1990 Oct; 21(10): 1412–8PubMedCrossRefGoogle Scholar
  68. 68.
    Shen AY, Yao JF, Brar SS, et al. Racial/ethnic differences in the risk of intracranial hemorrhage among patients with atrial fibrillation. J Am Coll Cardiol 2007 Jul 24; 50(4): 309–15PubMedCrossRefGoogle Scholar
  69. 69.
    van Walraven C, Hart RG, Singer DE, et al. Oral anticoagulants versus aspirin in nonvalvular atrial fibrillation: an individual patient meta-analysis. JAMA 2002 Nov 20; 288(19): 2441–8PubMedCrossRefGoogle Scholar
  70. 70.
    Fiore LD, Ezekowitz MD, Brophy MT, et al. Department of Veterans Affairs Cooperative Studies Program Clinical Trial comparing combined warfarin and aspirin with aspirin alone in survivors of acute myocardial infarction: primary results of the CHAMP study. Circulation 2002 Feb 5; 105(5): 557–63PubMedCrossRefGoogle Scholar
  71. 71.
    Hurlen M, Abdelnoor M, Smith P, et al. Warfarin, aspirin, or both after myocardial infarction. N Engl J Med 2002 Sep 26; 347(13): 969–74PubMedCrossRefGoogle Scholar
  72. 72.
    Albers GW, Diener HC, Frison L, et al. Ximelagatran versus warfarin for stroke prevention in patients with nonvalvular atrial fibrillation: a randomized trial. JAMA 2005 Feb 9; 293(6): 690–8PubMedCrossRefGoogle Scholar
  73. 73.
    Chimowitz MI, Lynn MJ, Howlett-Smith H, et al. Comparison of warfarin and aspirin for symptomatic intracranial arterial stenosis. N Engl J Med 2005 Mar 31; 352(13): 1305–16PubMedCrossRefGoogle Scholar
  74. 74.
    Buresly K, Eisenberg MJ, Zhang X, et al. Bleeding complications associated with combinations of aspirin, thienopyridine derivatives, and warfarin in elderly patients following acute myocardial infarction. Arch Intern Med 2005 Apr 11; 165(7): 784–9PubMedCrossRefGoogle Scholar
  75. 75.
    ACTIVE Writing Group on behalf of the ACTIVE Investigators. Clopidogrel plus aspirin versus oral anticoagulation for atrial fibrillation in the Atrial fibrillation Clopidogrel Trial with Irbesartan for prevention of Vascular Events (ACTIVE W): a randomised controlled trial. Lancet 2006 Jun 10; 367(9526): 1903–12CrossRefGoogle Scholar
  76. 76.
    Toyoda K, Yasaka M, Iwade K, et al. Dual antithrombotic therapy increases severe bleeding events in patients with stroke and cardiovascular disease: a prospective, multicenter, observational study. Stroke 2008 Jun; 39(6): 1740–5PubMedCrossRefGoogle Scholar
  77. 77.
    Radberg JA, Olsson JE, Radberg CT. Prognostic parameters in spontaneous intracerebral hematomas with special reference to anticoagulant treatment. Stroke 1991 May; 22(5): 571–6PubMedCrossRefGoogle Scholar
  78. 78.
    Hart RG, Boop BS, Anderson DC. Oral anticoagulants and intracranial hemorrhage: facts and hypotheses. Stroke 1995 Aug; 26(8): 1471–7PubMedCrossRefGoogle Scholar
  79. 79.
    Yasaka M, Minematsu K, Naritomi H, et al. Predisposing factors for enlargement of intracerebral hemorrhage in patients treated with warfarin. Thromb Haemost 2003 Feb; 89(2): 278–83PubMedGoogle Scholar
  80. 80.
    Flibotte JJ, Hagan N, O’Donnell J, et al. Warfarin, hematoma expansion, and outcome of intracerebral hemorrhage. Neurology 2004 Sep 28; 63(6): 1059–64PubMedCrossRefGoogle Scholar
  81. 81.
    Rosand J, Eckman MH, Knudsen KA, et al. The effect of warfarin and intensity of anticoagulation on outcome of intracerebral hemorrhage. Arch Intern Med 2004 Apr 26; 164(8): 880–4PubMedCrossRefGoogle Scholar
  82. 82.
    Toyoda K, Okada Y, Minematsu K, et al. Antiplatelet therapy contributes to acute deterioration of intracerebral hemorrhage. Neurology 2005 Oct 11; 65(7): 1000–4PubMedCrossRefGoogle Scholar
  83. 83.
    Saloheimo P, Ahonen M, Juvela S, et al. Regular aspirin-use preceding the onset of primary intracerebral hemorrhage is an independent predictor for death. Stroke 2006 Jan; 37(1): 129–33PubMedCrossRefGoogle Scholar
  84. 84.
    Roquer J, Rodriguez Campello A, Gomis M, et al. Previous antiplatelet therapy is an independent predictor of 30-day mortality after spontaneous supratentorial intracerebral hemorrhage. J Neurol 2005 Apr; 252(4): 412–6PubMedCrossRefGoogle Scholar
  85. 85.
    Toyoda K, Yasaka M, Nagata K, et al. Antithrombotic therapy influences location, enlargement, and mortality from intracerebral hemorrhage: the Bleeding with Antithrombotic Therapy (BAT) retrospective study. Cerebrovasc Dis 2009; 27(2): 151–9PubMedCrossRefGoogle Scholar

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© Adis Data Information BV 2009

Authors and Affiliations

  1. 1.Cerebrovascular Division, Department of MedicineNational Cardiovascular CenterOsakaJapan

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