Risk Stratification and Management of TIA and Minor Stroke

  • Alexandra D. MuccilliEmail author
  • Shelagh B. Coutts
  • Andrew M. Demchuk
  • Alexandre Y. Poppe


Together, transient ischemic attack (TIA) and minor stroke represent the largest group of cerebrovascular events, with one study estimating that over 80% of all stroke patients fall into this category [1]. With the advent of reperfusion therapies for acute ischemic stroke, systems of care have been streamlined such that patients with disabling or non-disabling deficits often present and are assessed very quickly after the onset of symptoms. Despite this, those with non-disabling deficits often fall into a therapeutic void since they are not considered eligible for thrombolysis or thrombectomy. This is particularly tragic since among patients considered too mild for thrombolytic therapy, up to one-third end up dead or dependent on being discharged from hospital [2, 3]. Furthermore, 15–30% of disabling strokes are heralded by non-disabling stroke or TIA, usually within the preceding 7 days [4]. Many studies have also demonstrated that after TIA or minor stroke, there is an approximately 10% risk of subsequent stroke within 90 days [5–13]. Functional disability may also affect about 15% of patients with TIA and minor stroke even in the absence of stroke recurrence [14]. Finally, as markers of vascular disease, TIAs predict an increased risk for all cardiovascular events and death in the longer term [5, 8]. Patients with mild cerebral ischemia represent an ideal target for therapy since they have a significant amount of tissue and function to safeguard in the face of an elevated early risk of major stroke.


  1. 1.
    Morgenstern LB, Lisabeth LD, Mecozzi AC, et al. A population-based study of acute stroke and TIA diagnosis. Neurology. 2004;62:865–900.CrossRefGoogle Scholar
  2. 2.
    Barber PA, Zhang J, Demchuk AM, et al. Why are stroke patients excluded from TPA therapy? An analysis of patient eligibility. Neurology. 2001;24:1015–20.CrossRefGoogle Scholar
  3. 3.
    Smith EE, Abdullah AR, Petkovska I, et al. Poor outcomes in patients who do not receive intravenous tissue plasminogen activator because of mild or improving ischemic stroke. Stroke. 2005;36:2497–9.PubMedCrossRefGoogle Scholar
  4. 4.
    Rothwell PM, Warlow C. Timing of TIAs preceding stroke: time window for prevention is very short. Neurology. 2005;64:817–20.PubMedCrossRefGoogle Scholar
  5. 5.
    Coull AJ, Lovett JK, Rothwell P. 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;328:326.PubMedPubMedCentralCrossRefGoogle Scholar
  6. 6.
    Eliasziw M, Kennedy J, Hill MD, et al. Early risk of stroke after a transient ischemic attack in patients with internal carotid artery disease. CMAJ. 2004;170:1105–9.PubMedPubMedCentralCrossRefGoogle Scholar
  7. 7.
    Hill MD, Yiannakoulias N, Jeerakathil T, et al. The high risk of stroke immediately after transient ischemic attack: a population-based study. Neurology. 2004;62:2015–20.PubMedCrossRefGoogle Scholar
  8. 8.
    Johnston SC, Gress DR, Browner WS, et al. Short-term prognosis after emergency department diagnosis of TIA. JAMA. 2000;284:2901–6.PubMedCrossRefGoogle Scholar
  9. 9.
    Dennis MS, Bamford JM, Sandercock PAG, et al. A comparison of risk factors and prognosis for transient ischemic attacks and minor ischemic strokes. Stroke. 1989;20:1494–9.PubMedCrossRefGoogle Scholar
  10. 10.
    Friedman GD, Wilson S, Mosier JM, et al. Transient ischemic attacks in a community. JAMA. 1969;210:1428–34.PubMedCrossRefGoogle Scholar
  11. 11.
    Gladstone DJ, Kapral MK, Fang J, et al. Management and outcomes of transient ischemic attacks in Ontario. CMAJ. 2004;170:1099–104.PubMedPubMedCentralCrossRefGoogle Scholar
  12. 12.
    Whisnant JP, Matsumoto N, Elveback L. Transient cerebral ischemic attacks in a community. Mayo Clin Proc. 1973;48:194–8.PubMedGoogle Scholar
  13. 13.
    Giles MF, Rothwell P. Risk of stroke early after transient ischaemic attack: a systematic review and meta-analysis. Lancet Neurol. 2007;6:1063–72.PubMedCrossRefGoogle Scholar
  14. 14.
    Coutts SB, Modi J, Patel SK. What causes disability after transient ischemic attack and minor stroke? Stroke. 2012;43:3018–22.PubMedCrossRefGoogle Scholar
  15. 15.
    Albers GW, Caplan LR, Easton JD, et al. Transient ischemic attack—proposal for a new definition. N Engl J Med. 2002;347:1713–6.PubMedCrossRefGoogle Scholar
  16. 16.
    Levy D. How transient are transient ischemic attacks? Neurology. 1988;38:674–7.PubMedCrossRefGoogle Scholar
  17. 17.
    Marler JR, Tilley BC, Lu M, et al. Early stroke treatment associated with better outcome: the NINDS rt-PA stroke study. Neurology. 2000;55:1649–55.PubMedCrossRefGoogle Scholar
  18. 18.
    Pessin MS, Duncan GW, Mohr JP, et al. Clinical and angiographic features of carotid transient ischemic attacks. N Engl J Med. 1977;296:358–62.PubMedCrossRefGoogle Scholar
  19. 19.
    Weisberg L. Clinical characteristics of transient ischemic attacks in black patients. Neurology. 1991;41:1410–4.PubMedCrossRefGoogle Scholar
  20. 20.
    Ay H, Oliveira-Filho J, Buonanno FS, et al. ‘Footprints’ of transient ischemic attacks: a diffusion-weighted MRI study. Cerebrovasc Dis. 2002;14:177–86.PubMedCrossRefGoogle Scholar
  21. 21.
    Crisostomo RA, Garcia MM, Tong D. Detection of diffusion-weighted MRI abnormalities in patients with transient ischemic attack: correlation with clinical characteristics. Stroke. 2003;34:932–7.PubMedCrossRefGoogle Scholar
  22. 22.
    Inatomi Y, Kimura K, Yonehara T, et al. DWI abnormalities and clinical characteristics in TIA patients. Neurology. 2004;62:376–80.PubMedCrossRefGoogle Scholar
  23. 23.
    Kidwell CS, Alger JR, Di Salle F, et al. Diffusion MRI in patients with transient ischemic attacks. Stroke. 1999;6:1174–80.CrossRefGoogle Scholar
  24. 24.
    Rovira A, Rovira-Gols A, Pedraza S, et al. Diffusion-weighted MR imaging in the acute phase of transient ischemic attacks. AJNR. 2002;23:77–83.PubMedGoogle Scholar
  25. 25.
    Warach S, Kidwell C. The redefinition of TIA: the uses and limitations of DWI in acute ischemic cerebrovascular syndromes. Neurology. 2004;62:359–60.PubMedCrossRefGoogle Scholar
  26. 26.
    Dávalos A, Matías-Guiu J, Torrent O, et al. Computed tomography in reversible ischaemic attacks: clinical and prognostic correlations in a prospective study. J Neurol. 1988;235:155–8.PubMedCrossRefGoogle Scholar
  27. 27.
    Ay H, Buonanno FS, Rordorf G, et al. Normal diffusion-weighted MRI during stroke-like deficits. Neurology. 1999;10:1784–92.CrossRefGoogle Scholar
  28. 28.
    Engelter ST, Provenzale JM, Petrella JR, et al. Diffusion MR imaging and transient ischemic attacks. Stroke. 1999;30:2762–3.PubMedCrossRefGoogle Scholar
  29. 29.
    Easton JD, Saver JL, Albers GW, et al. Definition and evaluation of transient ischemic attack. Stroke. 2009;40:2276–93.PubMedCrossRefGoogle Scholar
  30. 30.
    Lovett JK, Dennis MS, Sandercock PA, et al. Very early risk of stroke after a first transient ischemic attack. Stroke. 2003;34:e138–40.PubMedCrossRefGoogle Scholar
  31. 31.
    Daffertshofer M, Mielke O, Pullwitt A, et al. Transient ischemic attacks are more than ‘ministrokes’. Stroke. 2004;35:2453–8.PubMedCrossRefGoogle Scholar
  32. 32.
    Lisabeth LD, Ireland JK, Risser JM, et al. Stroke risk after transient ischemic attack in a population-based setting. Stroke. 2004;35:1842–6.PubMedCrossRefGoogle Scholar
  33. 33.
    Chandratheva A, Mehta Z, Geraghty O, et al.; on behalf of the Oxford Vascular Study. Population-based study of risk and predictors of stroke in the first few hours after a TIA. Neurology. 2009;2:1941–7.Google Scholar
  34. 34.
    Rothwell PM, Giles MF, Flossmann E, et al. A simple score (ABCD) to identify individuals at high early risk of stroke after transient ischaemic attack. Lancet. 2005;366:29–36.PubMedCrossRefPubMedCentralGoogle Scholar
  35. 35.
    Johnston SC, Rothwell PM, Nguyen-Huynh MN, et al. Validation and refinement of scores to predict very early stroke risk after transient ischaemic attack. Lancet. 2007;369:283–92.PubMedCrossRefPubMedCentralGoogle Scholar
  36. 36.
    Wang J, Wu J, Liu R, et al. The ABCD2 score is better for stroke risk prediction after anterior circulation TIA compared to posterior circulation TIA. Int J Neurosci. 2015;125:50–5.PubMedCrossRefPubMedCentralGoogle Scholar
  37. 37.
    Wardlaw JM, Brazzelli M, Chappell FM, et al. ABCD2 score and secondary stroke prevention: meta-analysis and effect per 1,000 patients triaged. Neurology. 2015;85:373.PubMedPubMedCentralCrossRefGoogle Scholar
  38. 38.
    Coutts SB, Barrett KM. TIA risk stratification. Neurology. 2015;85:1–2.CrossRefGoogle Scholar
  39. 39.
    Purroy F, Jimenez Caballero PE, Gorospe A, et al. Prediction of early stroke recurrence in transient ischemic attack patients from the PROMAPA study: a comparison of prognostic risk scores. Cerebrovasc Dis. 2012;33:182–9.PubMedCrossRefGoogle Scholar
  40. 40.
    Coutts SB, Modi J, Patel SK, et al. CT/CT angiography and MRI findings predict recurrent stroke after transient ischemic attack and minor stroke: results of the prospective CATCH study. Stroke. 2012;43:1013–7.PubMedCrossRefPubMedCentralGoogle Scholar
  41. 41.
    Coutts SB, Hill MD, Simon JE, et al. Silent ischemia in minor stroke and TIA patients identified on MR imaging. Neurology. 2005;65:513–7.PubMedCrossRefPubMedCentralGoogle Scholar
  42. 42.
    Calanchini PR, Swanson PD, Gotshall RA, et al. Cooperative study of hospital frequency and character of transient ischemic attacks. IV. The reliability of diagnosis. JAMA. 1977;238:2029–33.PubMedCrossRefPubMedCentralGoogle Scholar
  43. 43.
    Ferracci F, Moretto G, Gentile M, et al. Can seizures be the only manifestation of transient ischemic attacks? A report of four cases. Neurol Sci. 2000;21:303–6.PubMedCrossRefPubMedCentralGoogle Scholar
  44. 44.
    García-Moncó JC, Marrodán A, Foncea Beti N, et al. Stroke and transient ischemic attack-mimicking conditions: A prospective analysis of risk factors and clinical profiles at a general hospital. Neurologia. 2002;17:355–60.PubMedPubMedCentralGoogle Scholar
  45. 45.
    Libman RB, Wirkowski E, Alvir J, et al. Conditions that mimic stroke in the emergency department. Implications for acute stroke trials. Arch Neurol. 1995;52:1119–22.PubMedCrossRefGoogle Scholar
  46. 46.
    Moster ML, Johnston DE, Reinmuth O. Chronic subdural hematoma with transient neurological deficits: a review of 15 cases. Ann Neurol. 1983;14:539–42.PubMedCrossRefGoogle Scholar
  47. 47.
    Nor AM, Davis J, Sen B, et al. The Recognition of Stroke in the Emergency Room (ROSIER) scale: development and validation of a stroke recognition instrument. Lancet Neurol. 2005;4:727–34.PubMedCrossRefGoogle Scholar
  48. 48.
    Josephson SA, Sidney S, Pham TN, et al. Higher ABCD2 score predicts patients most likely to have true transient ischemic attack. Stroke. 2008;39:3096–8.PubMedCrossRefGoogle Scholar
  49. 49.
    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;6:953–60.PubMedCrossRefGoogle Scholar
  50. 50.
    Coutts SB, Hill MD, Campos CR, et al. Recurrent events in transient ischemic attack and minor stroke: What events are happening and to which patients? Stroke. 2008;39:2461–6.PubMedCrossRefGoogle Scholar
  51. 51.
    Johnston SC, Easton J. Are patients with acutely recovered cerebral ischemia more unstable? Stroke. 2003;34:2446–50.PubMedCrossRefGoogle Scholar
  52. 52.
    Johnston SC, Leira EC, Hansen MD, et al. Early recovery after cerebral ischemia risk of subsequent neurological deterioration. Ann Neurol. 2003;54:439–44.PubMedCrossRefGoogle Scholar
  53. 53.
    Purroy F, Montaner J, Molina CA, et al. Patterns and predictors of early risk of recurrence after transient ischemic attack with respect to etiologic subtypes. Stroke. 2007;38:3225–9.PubMedCrossRefGoogle Scholar
  54. 54.
    Lovett JK, Coull AJ, Rothwell P. Early risk of recurrence by subtype of ischemic stroke in population-based incidence studies. Neurology. 2004;62:569–73.PubMedCrossRefGoogle Scholar
  55. 55.
    Rothwell PM, Eliasziw M, Gutnikov SA, et al. Endarterectomy for symptomatic carotid stenosis in relation to clinical subgroups and timing of surgery. Lancet. 2004;363:915–24.PubMedCrossRefGoogle Scholar
  56. 56.
    Ovbiagele B, Cruz-Flores S, Lynn MJ, et al. Early stroke risk after transient ischemic attack among individuals with symptomatic intracranial artery stenosis. Arch Neurol. 2008;65:733–7.PubMedCrossRefGoogle Scholar
  57. 57.
    Gulli G, Khan S, Markus HS. Vertebrobasilar stenosis predicts high early recurrent stroke risk in posterior circulation stroke and TIA. Stroke. 2009;40:2732–7.PubMedCrossRefGoogle Scholar
  58. 58.
    Douglas VC, Johnston CM, Elkins J, et al. Head computed tomography findings predict short-term stroke risk after transient ischemic attack. Stroke. 2003;34:2894–8.PubMedCrossRefGoogle Scholar
  59. 59.
    Dennis M, Bamford J, Sandercock P, et al. Computed tomography in patients with transient ischaemic attacks: When is a transient ischaemic attack not a transient ischaemic attack but a stroke? J Neurol. 1990;237:257–61.PubMedCrossRefPubMedCentralGoogle Scholar
  60. 60.
    Evans GW, Howard G, Murros KE, et al. Cerebral infarction verified by cranial computed tomography and prognosis for survival following transient ischemic attack. Stroke. 1991;22:431–6.PubMedCrossRefGoogle Scholar
  61. 61.
    Rothwell PM, Eliasziw M, Gutnikov SA, et al. Endarterectomy for symptomatic carotid stenosis in relation to clinical subgroups and timing of surgery. Lancet. 2004;363:915–24.PubMedCrossRefGoogle Scholar
  62. 62.
    Josephson SA, Bryant SO, Mak HK, et al. Evaluation of carotid stenosis using CT angiography in the initial evaluation of stroke and TIA. Neurology. 2004;10:457–60.CrossRefGoogle Scholar
  63. 63.
    Bash S, Villablanca JP, Jahan R, et al. Intracranial vascular stenosis and occlusive disease: evaluation with CT angiography, MR angiography, and digital subtraction angiography. AJNR. 2005;26:1012–21.PubMedGoogle Scholar
  64. 64.
    Schramm P, Schellinger PD, Fiebach JB, et al. Comparison of CT and CT angiography source images with diffusion-weighted imaging in patients with acute stroke within 6 hours after onset. Stroke. 2002;33:2426–32.PubMedCrossRefGoogle Scholar
  65. 65.
    Randoux B, Marro B, Koskas F, et al. Carotid artery stenosis: prospective comparison of CT, three-dimensional gadolinium-enhanced MR, and conventional angiography. Radiology. 2001;220:179–85.PubMedCrossRefGoogle Scholar
  66. 66.
    Yaghi S, Rostanski SK, Boehme AK, et al. Imaging parameters and recurrent cerebrovascular events in patients with minor stroke or transient ischemic attack. JAMA Neurol. 2016;73:572–8.PubMedPubMedCentralCrossRefGoogle Scholar
  67. 67.
    Kamal N, Blacquiere DP, Boulanger JM, et al. Rapid assessment and treatment of transient ischemic attacks and minor stroke in Canadian emergency departments: time for a paradigm shift. Stroke. 2015;46:2987–90.PubMedCrossRefGoogle Scholar
  68. 68.
    Awad I, Modic M, Little JR, et al. Focal parenchymal lesions in transient ischemic attacks: correlation of computed tomography and magnetic resonance imaging. Stroke. 1986;17:399–403.PubMedCrossRefGoogle Scholar
  69. 69.
    Chalela JA, Kidwell CS, Nentwich LM, et al. Magnetic resonance imaging and computed tomography in emergency assessment of patients with suspected acute stroke: a prospective comparison. Lancet. 2007;369:293–8.PubMedPubMedCentralCrossRefGoogle Scholar
  70. 70.
    Flossmann E, Redgrave JN, Briley D, et al. Reliability of clinical diagnosis of the symptomatic vascular territory in patients with recent transient ischemic attack or minor stroke. Stroke. 2008;39:2457–60.PubMedCrossRefGoogle Scholar
  71. 71.
    Kang DW, Chalela JA, Ezzeddine MA, et al. Association of ischemic lesion patterns on early diffusion-weighted imaging with TOAST stroke subtypes. Arch Neurol. 2003;60:1730–4.PubMedCrossRefGoogle Scholar
  72. 72.
    Lee LJ, Kidwell CS, Alger J, et al. Impact on stroke subtype diagnosis of early diffusion-weighted magnetic resonance imaging and magnetic resonance angiography. Stroke. 2000;31:1081–9.PubMedCrossRefGoogle Scholar
  73. 73.
    Coutts SB, Simon JE, Eliasziw M, et al. Triaging transient ischemic attack and minor stroke patients using acute magnetic resonance imaging. Ann Neurol. 2005;57:848–54.PubMedCrossRefGoogle Scholar
  74. 74.
    Purroy F, Montaner J, Rovira A, et al. Higher risk of further vascular events among transient ischemic attack patients with diffusion-weighted imaging acute ischemic lesions. Stroke. 2004;35:2313–9.PubMedCrossRefGoogle Scholar
  75. 75.
    Coutts SB, Eliasziw M, Hill MD, et al. The functional impairment risk score (FIRS) identifies patients at high risk of disability after TIA or minor stroke. Cerebrovasc Dis. 2007;23(Suppl 2):28.Google Scholar
  76. 76.
    Coutts SB, O’Reilly C, Hill MD, et al. CT and CT angiography findings predict functional impairment in patients with minor stroke and TIA. Int J Stroke. 2009;4:448–53.PubMedCrossRefGoogle Scholar
  77. 77.
    Ois A, Gomis M, Rodríguez-Campello A, et al. Factors associated with a high risk of recurrence in patients with transient ischemic attack or minor stroke. Stroke. 2008;39:1717–21.PubMedCrossRefGoogle Scholar
  78. 78.
    Torres-Mozqueda F, He J, Yeh IB, et al. An acute ischemic stroke classification instrument that includes CT or MR angiography: the Boston Acute Stroke Imaging Scale. AJNR. 2008;29:1111–7.PubMedCrossRefGoogle Scholar
  79. 79.
    Davis DP, Robertson T, Imbesi SG. Diffusion-weighted magnetic resonance imaging versus computed tomography in the diagnosis of acute ischemic stroke. J Emerg Med. 2006;31:269–77.PubMedCrossRefGoogle Scholar
  80. 80.
    Mehdiratta M, Selim M. Value of perfusion computed tomography in stroke mimics. JAMA Neurol. 2007;64:1348–9.Google Scholar
  81. 81.
    Prabhalaram S, Patel S, Samuels J, et al. Perfusion computed tomography in transient ischemic attack. Arch Neurol. 2011;68:85–9.Google Scholar
  82. 82.
    Kleinman JT, Mlynash M, Zaharchuk G, et al. Yield of CT perfusion for the evaluation of transient ischemic attack. Int J Stroke. 2015;10:25–9.PubMedCrossRefGoogle Scholar
  83. 83.
    Van der Wijgaard IR, Algra A, Lycklama GJ, et al. Value of whole brain computed tomography perfusion for predicting outcome after TIA or minor ischemic stroke. J Stroke Cerebrovas Dis. 2015;24:2081–7.CrossRefGoogle Scholar
  84. 84.
    Markus H. Monitoring embolism in real time. Circulation. 2000;102:826–8.PubMedCrossRefGoogle Scholar
  85. 85.
    Markus HS, MacKinnon A. Asymptomatic embolization detected by Doppler ultrasound predicts stroke risk in symptomatic carotid artery stenosis. Stroke. 2005;36:971–5.PubMedCrossRefGoogle Scholar
  86. 86.
    Valton L, Larrue V, le Traon AP, et al. Microembolic signals and risk of early recurrence in patients with stroke or transient ischemic attack. Stroke. 1998;29:2125–8.PubMedCrossRefGoogle Scholar
  87. 87.
    Levi CR, Roberts AK, Fell G, et al. Transcranial Doppler microembolus detection in the identification of patients at high risk of perioperative stroke. Eur J Vasc Endovasc Surg. 1997;14:170–6.PubMedCrossRefGoogle Scholar
  88. 88.
    Coutts SB, Eliasziw M, Hill MD, et al. An improved scoring system for identifying patients at high early risk of stroke and functional impairment after an acute transient ischemic attack or minor stroke. Int J Stroke. 2008;3:3–10.PubMedCrossRefGoogle Scholar
  89. 89.
    Calvet D, Touze E, Oppenheim C, et al. DWI lesions and TIA etiology improve the prediction of stroke after TIA. Stroke. 2009;40:187–92.PubMedCrossRefGoogle Scholar
  90. 90.
    Halkes PH, van Gijn J, Kappelle LJ, et al. Aspirin plus dipyridamole versus aspirin alone after cerebral ischaemia of arterial origin (ESPRIT): randomised controlled trial. Lancet. 2006;367:1665–73.PubMedCrossRefGoogle Scholar
  91. 91.
    Sandercock PA, Counsell C, Kamal A. Anticoagulants for acute ischaemic stroke. Cochrane Database Syst Rev. 2008:CD000024.Google Scholar
  92. 92.
    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, placebo-controlled trial. Lancet. 2004;364:331–7.PubMedCrossRefGoogle Scholar
  93. 93.
    Johnston SC, Nguyen-Huynh MN, Schwarz ME, et al. National Stroke Association guidelines for the management of transient ischemic attacks. Ann Neurol. 2006;60:301–13.PubMedCrossRefGoogle Scholar
  94. 94.
    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;133(6. Suppl):630S–69S.PubMedCrossRefGoogle Scholar
  95. 95.
    Johnston SC, Amarenco P, Albers GW, et al. Ticagrelor versus aspirin in acute stroke or transient ischemic attack. N Engl J Med. 2016;375:35–43.PubMedCrossRefGoogle Scholar
  96. 96.
    Kim JT, Parks MS, Choi KH, et al. Different antiplatelet strategies in patients with new ischemic stroke while taking aspirin. Stroke. 2016;47:128–34.PubMedCrossRefGoogle Scholar
  97. 97.
    Coutts SB, Wein TH, Lindsay MP, et al. Canadian stroke best practice recommendations: secondary prevention of stroke guidelines, update 2014. Int J Stroke. 2015;10:282–91.PubMedCrossRefGoogle Scholar
  98. 98.
    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;370:1432–42.PubMedCrossRefGoogle Scholar
  99. 99.
    The International Stroke Trial (IST): a randomised trial of aspirin, subcutaneous heparin, both, or neither among 19435 patients with acute ischaemic stroke. International Stroke Trial Collaborative Group. Lancet. 1997;349:1569–81.Google Scholar
  100. 100.
    CAST: Randomised placebo-controlled trial of early aspirin use in 20,000 patients with acute ischaemic stroke. CAST (Chinese Acute Stroke Trial) Collaborative Group. Lancet. 1997;349:1641–9.Google Scholar
  101. 101.
    Chen ZM, Sandercock P, Pan HC, et al. Indications for early aspirin use in acute ischemic stroke: a combined analysis of 40000 randomized patients from the Chinese Acute Stroke Trial and the International Stroke Trial. On behalf of the CAST and IST collaborative groups. Stroke. 2000;31:1240–9.PubMedCrossRefGoogle Scholar
  102. 102.
    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;143:1–13.PubMedCrossRefGoogle Scholar
  103. 103.
    Sacco RL, Diener HC, Yusuf S, et al. Aspirin and extended-release dipyridamole versus clopidogrel for recurrent stroke. N Engl J Med. 2008;359:1238–51.PubMedPubMedCentralCrossRefGoogle Scholar
  104. 104.
    Gent M, Beaumont D, Blanchard J, et al. A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). CAPRIE Steering Committee. Lancet. 1996;348:1329–39.CrossRefGoogle Scholar
  105. 105.
    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;111:2233–40.PubMedCrossRefGoogle Scholar
  106. 106.
    Kennedy J, Hill MD, Ryckborst KJ, et al. Fast assessment of stroke and transient ischaemic attack to prevent early recurrence (FASTER): a randomised controlled pilot trial. Lancet Neurol. 2007;6:961–9.PubMedCrossRefGoogle Scholar
  107. 107.
    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;354:1706–17.PubMedCrossRefGoogle Scholar
  108. 108.
    Wang Y, Wang Y, Zhao X, et al. Clopidogrel with aspirin in acute minor stroke or transient ischemic attack. N Engl J Med. 2013;369:11–9.PubMedCrossRefGoogle Scholar
  109. 109.
    Han Y, Lv HH, Liu X, et al. Influence of genetic polymorphisms on clopidogrel response and clinical outcomes in patients with acute ischemic stroke CYP2C19 genotype on clopidogrel response. CNS Neurosci Ther. 2015;21:692–7.PubMedPubMedCentralCrossRefGoogle Scholar
  110. 110.
    Johnston SC, Easton JD, Farrant M, et al. Platelet-oriented inhibition in new TIA and minor ischemic stroke (POINT) trial: rationale and design. Int J Stroke. 2013;8:479–83.PubMedPubMedCentralCrossRefGoogle Scholar
  111. 111.
    TARDIS Trial Investigators, Krishnan K, Beridze M, Christensen H, et al. Safety and efficacy of intensive vs. guideline antiplatelet therapy in high-risk patients with recent ischemic stroke or transient ischemic attack: rationale and design of the Triple Antiplatelets for Reducing Dependency after Ischaemic Stroke (TARDIS) trial. Int J Stroke. 2015;10:1159–65.CrossRefGoogle Scholar
  112. 112.
    Côté R, Zhang Y, Hart RG, et al. ASA failure: does the combination ASA/clopidogrel confer better long-term vascular protection? Neurology. 2014;82:382–9.PubMedPubMedCentralCrossRefGoogle Scholar
  113. 113.
    Connolly SJ, Ezekowitz MD, Yusuf S, et al. Dabigatran versus warfarin in patients with atrial fibrillation. NEJM. 2009;361:1139–51.PubMedCrossRefGoogle Scholar
  114. 114.
    Patel MR, Mahaffey KW, Garg J, et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. NEJM. 2011;365:883–91.PubMedCrossRefGoogle Scholar
  115. 115.
    Granger CB, Alexander JH, McMurray JJV, et al. Apixaban versus warfarin in patients with atrial fibrillation. NEJM. 2011;365:981–92.PubMedCrossRefGoogle Scholar
  116. 116.
    Low molecular weight heparinoid, ORG 10172 (danaparoid), and outcome after acute ischemic stroke: a randomized controlled trial. The Publications Committee for the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) Investigators. JAMA. 1998;279:1265–72.Google Scholar
  117. 117.
    Rothwell PM, Eliasziw M, Gutnikov SA, et al. Analysis of pooled data from the randomised controlled trials of endarterectomy for symptomatic carotid stenosis. Lancet. 2003;361:107–16.PubMedCrossRefGoogle Scholar
  118. 118.
    Rothwell PM, Eliasziw M, Gutnikov SA, et al. Sex difference in the effect of time from symptoms to surgery on benefit from carotid endarterectomy for transient ischemic attack and nondisabling stroke. Stroke. 2004;35:2855–61.PubMedCrossRefGoogle Scholar
  119. 119.
    Bond R, Rerkasem K, Rothwell P. Systematic review of the risks of carotid endarterectomy in relation to the clinical indication for and timing of surgery. Stroke. 2003;34:2290–301.PubMedCrossRefGoogle Scholar
  120. 120.
    Taylor DW, Barnett HJ, Haynes RB, et al. Low-dose and high-dose acetylsalicylic acid for patients undergoing carotid endarterectomy: a randomised controlled trial. ASA and Carotid Endarterectomy (ACE) Trial Collaborators. Lancet. 1999;26:2179–84.CrossRefGoogle Scholar
  121. 121.
    Payne DA, Jones CI, Hayes PD, et al. Beneficial effects of clopidogrel combined with aspirin in reducing cerebral emboli in patients undergoing carotid endarterectomy. Circulation. 2004;109:1476–81.PubMedCrossRefGoogle Scholar
  122. 122.
    Wiesmann M, Schöpf V, Jansen O, et al. Stent-protected angioplasty versus carotid endarterectomy in patients with carotid artery stenosis: meta-analysis of randomized trial data. Eur Radiol. 2008;18:2956–66.PubMedCrossRefGoogle Scholar
  123. 123.
    Recombinant tissue plasminogen activator for minor strokes: The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study experience. Ann Emerg Med. 2005;46:243–52.Google Scholar
  124. 124.
    Mann J. tPA for acute stroke: balancing baseline imbalances. CMAJ. 2002;166:1651–3.PubMedPubMedCentralGoogle Scholar
  125. 125.
    Khatri P, Tamaya D, Cohen G, et al. Effects of intravenous recombinant tissue-type plasminogen activator in patients with mild stroke in the third international stroke trial-3: Post-hoc analysis. Stroke. 2015;46:2325–7.PubMedCrossRefGoogle Scholar
  126. 126.
    Emberson J, Lees KR, Lyden P, et al. Effects of treatment delay, age, and stroke severity on the effects of intravenous thrombolysis with alteplase for acute ischemic stroke: a meta-analysis of individual patient data from randomized trials. Lancet. 2014;384:1929–35.PubMedPubMedCentralCrossRefGoogle Scholar
  127. 127.
    Coutts SB, Dubuc V, Mandzia J, et al. Tenecteplase-tissue-type plasminogen activator evaluation for minor ischemic stroke with proven occlusion. Stroke. 2015;46:769–74.PubMedCrossRefGoogle Scholar
  128. 128.
    Tanswell P, Modi N, Combs D, Danyas T. Pharmacokinetics and pharmacodynamics of tenecteplase in fibrinolytic therapy of acute myocardial infarction. Clin Pharmacokinet. 2002;41:1229–45.PubMedCrossRefGoogle Scholar
  129. 129.
    Parsons M, Spratt N, Bivard A, et al. A randomized trial of tenecteplase versus alteplase for acute ischemic stroke. N Engl J Med. 2012;366:1099–107.PubMedCrossRefGoogle Scholar
  130. 130.
    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
  131. 131.
    Smith EE, Abdullah AR, Petkovska I, et al. Poor outcomes in patients who do not receive intravenous plasminogen activator because of mild or improving ischemic stroke. Stroke. 2005;36:2497–9.PubMedCrossRefGoogle Scholar

Copyright information

© The Author(s) 2019

Authors and Affiliations

  • Alexandra D. Muccilli
    • 1
    Email author
  • Shelagh B. Coutts
    • 2
  • Andrew M. Demchuk
    • 2
  • Alexandre Y. Poppe
    • 1
  1. 1.Department of NeurosciencesCentre Hospitalier de l’Université de Montréal, Hôpital Notre-Dame, Université de MontréalMontrealCanada
  2. 2.Department of Clinical NeurosciencesFoothills Medical Centre, University of CalgaryCalgaryCanada

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