Intravenous thrombolysis in ischemic stroke: clinical predictors of efficacy and safety

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Abstract

Introduction. Systemic thrombolysis with recombinant tissue plasminogen activator is the “gold standard” of reperfusion therapy, having the maximum level of evidence in European and North American guidelines for the treatment of patients with acute ischemic stroke (IS).
Objective: to determine factors of individual efficacy and safety of systemic thrombolysis in patients with IS aiming to establish personalized approach to its optimization.
Materials and methods. The study included 396 patients with IS, of whom 196 patients underwent systemic thrombolysis with recombinant tissue plasminogen activator and 200 patients formed the control group. A prospective non-randomized study was conducted in parallel groups to estimate efficacy and safety of systemic thrombolysis with recombinant tissue plasminogen activator. The primary endpoint of the study was functional independence of patients measured with a modified Rankin scale 3 months after the stroke.

Results. We confirmed improvement of the functional outcome in patients with IS who underwent systemic thrombolysis. We also showed no effect of thrombolytic therapy on the mortality rates. Decreased wakefulness, presence of aphasia, hemiplegia, congestive heart failure, type 2 diabetes, postinfarction cardiosclerosis were shown to be clinical factors associated with an unfavorable prognosis of the disease after systemic thrombolysis. We found higher likelihood of death in patients with decreased level of consciousness (OR 3.1 (1.1–8.8); p=0.03), as well as with paresis (OR 6.8 (2.2–20.9); p<0.001), hemiplegia (OR 6.5 (2.0–21.4); p=0.002), and chronic heart failure (OR 2.4 (1.1–5.3); p=0.03).

Conclusion. Adequate analysis of neurological symptoms and clinical and anamnestic data upon admission of a patient with IS allows to predict the effectiveness of thrombolysis and may be important in treatment planning and in choosing reperfusion methods.

About the authors

Maksim A. Domashenko

Botkin Сity Clinic Hospital

Author for correspondence.
Email: mdomashenko@gmail.com
Russian Federation, Moscow

Marina Yu. Maksimova

Research Center of Neurology, Moscow

Email: neurocor@mail.ru
ORCID iD: 0000-0002-7682-6672
Russian Federation, Moscow, Volokolamskoe shosse,80

Marine M. Tanashyan

Research Center of Neurology

Email: mdomashenko@gmail.com
Russian Federation, Moscow

References

  1. Suslina Z.A., Tanashyan M.M., Ionova V.G. [Ischemic stroke: blood, vessel wall and antithrombotic treatment]. Moscow, 2005. 248 p. (In Russ.)
  2. Szikszai Z., Fekete I., Imre S.G. A comparative study of hemorheological parameters in transient ischemic attack and acute ischemic stroke patients: possible predictive value. Clin Hemorheol Microcirc 2003; 28: 51–57. PMID: 12632012.
  3. Suslina Z.A., Tanashyan M.M., Domashenko M.A. [Antithrombotic treatment of the stroke]. Moscow, 2009. 224 p. (In Russ.)
  4. Guidelines for Management of Ischaemic Stroke of the European Stroke Organisation, 2008. URL: http://www.eso-stroke.org/recommendations.
  5. Jauch E.C., Saver J.L., Adams H.P. et al; American Heart Association Stroke Council; Council on Cardiovascular Nursing; Council on Peripheral Vascular Disease; Council on Clinical Cardiology. Guidelines for the Early Management of Patients with Acute Ischemic Stroke. A Guideline for Healthcare Professionals from the American Heart Association/American Stroke Association. Stroke 2013; 44: 870–947. doi: 10.1161/STR.0b013e318284056a. PMID: 23370205.
  6. Emberson J., Lees K.R., Lyden P. et al. Effect of treatment delay, age, and stroke severity on the effects of intravenous thrombolysis with alteplase for acute ischaemic stroke: a meta-analysis of individual patient data from randomised trials. Lancet 2014; 384: 1929–1235. doi: 10.1016/S0140-6736(14)60584-5. PMID: 25106063.
  7. Lees K.R., Emberson J., Blackwell L. et al. Effects of аlteplase for acute stroke on the distribution of functional outcomes: a pooled analysis of 9 trials. Stroke 2016; 47: 2373–2379. doi: 10.1161/STROKEAHA.116.013644. PMID: 27507856.
  8. Skvortzova V.I., Golukhov G.N., Gubskiy L.V. et al. [Systemic thrombolytic therapy for ischemic stroke]. Zhurnal nevrologii i psikhiaytrii imeni S.S. Korsakova. 2006; 106(12): 24–31. (In Russ.)
  9. Domashenko M.A., Maksimova M.Yu., Loskutnikov M.A. et al. [Intravenous thrombolysis in acute ischemic stroke]. Annals of clinical and experimental neurology. 2008; (2): 5–12. (In Russ.)
  10. Domashenko M.A., Maksimova M.Yu., Loskutnikov M.A. et al. [Reperfusion mechanisms for intravenous thrombolytic therapy in patients with ischemic stroke]. Nevrologiya, neyropsikhiatriya, psikhosomatika. 2012; (4): 53–58. (In Russ.)
  11. Piradov M.A., Domashenko M.A., Maksimova M.Yu. [Reperfusion treatment of ischemic stroke]. In: M.A. Piradov, S.N. Illarioshkin, M.M. Tanashyan (eds.) [Neurology of the XXI Century: Diagnostic, Medical and Research Technologies: A Guide for Doctors]. Moscow, 2015. II: 9–45. (In Russ.)
  12. Skvortzova V.I., Stakhovskaya L.V., Lelyuk V.G et al. [Modernization of stroke care system in Russian Federation]. In: [Materials of the Russian conference «Modernization of care system of patients with cerebrovascular diseases»]. Yaroslavl, 2011: 13–33. (In Russ.)
  13. Shamalov N.A. [Problems and perspectieves of reperfusion therapy of ischemic stroke in Russia]. Pharmateka 2015; (9): 14–19. (In Russ.)
  14. Berkhemer O.A., Fransen P.S.S, Beumer D. et al. A randomized trial of intraarterial treatment for acute ischemic stroke. N Engl J Med 2015; 372: 11–20. doi: 10.1056/NEJMoa1411587. PMID: 25517348.
  15. Goyal M., Demchuk A.M., Menon B.K. et al Randomized assessment of rapid endovascular treatment of ischemic stroke. N Engl J Med 2015; 372: 1019–1030. doi: 10.1056/NEJMoa1414905. PMID: 25671798.
  16. Campbell B.C., Mitchell P.J., Kleinig T.J. et al. Endovascular therapy for ischemic stroke with perfusion-imaging selection. N Engl J Med 2015; 372: 1009–1018. doi: 10.1056/NEJMoa1414792. PMID: 25671797.
  17. Saver J.L., Goyal M., Bonafe A. et al; SWIFT PRIME Investigators. Stent-retriever thrombectomy after intravenous t-PA vs. t-PA alone in stroke. N Engl J Med 2015; 372: 2285–2295. doi: 10.1056/NEJMoa1415061. PMID: 25882376.
  18. Jovin T.G., Chamorro A., Cobo E. et al. Thrombectomy within 8 hours after symptom onset in ischemic stroke. N Engl J Med 2015; 372: 2296–2306. doi: 10.1056/NEJMoa1503780. PMID: 25882510.
  19. Goyal M., Menon B.K., van Zwam W.H. et al. Endovascular thrombectomy after large-vessel ischaemic stroke: a meta-analysis of individual patient data from five randomised trials. Lancet 2016; 387: 1723–1731. doi: 10.1016/S0140-6736(16)00163-X. PMID: 26898852.
  20. Powers W.J., Derdeyn C.P., Biller J. et al. 2015 American Heart Association/American Stroke Association focused update of the 2013 guidelines for the early management of patients with acute ischemic stroke regarding endovascular treatment. A Guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2015; 46: 3020–3035. doi: 10.1161/STR.0000000000000074. PMID: 26123479.
  21. Mistry E.A., Mistry A.M., Nakawah M.O. et al. Mechanical thrombectomy outcomes with and without intravenous thrombolysis in stroke patients. A meta-analysis. Stroke 2017; 48: 2450–2456. doi: 10.1161/STROKEAHA.117.017320. PMID: 28747462.
  22. Nogueira R.G., Jadhav A.P., Haussen D.C. et al. Thrombectomy 6 to 24 hours after stroke with a mismatch between deficit and infarct. N Eng J Med 2018; 378: 11–21. doi: 10.1056/NEJMoa1706442. PMID: 29129157.
  23. Albers G.W., Marks M.P., Kemp S. et al. Thrombectomy for stroke at 6 to 16 hours with selection by perfusion imaging. N Engl J Med 2018; 378: 708–718. doi: 10.1056/NEJMoa1713973. PMID: 29364767.
  24. Powers W.J., Rabinstein A.A., Ackerson T. еt al.; American Heart Association Stroke Council. 2018 Guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2018; 49: e46–e110. doi: 10.1161/STR.0000000000000158. PMID: 29367334.
  25. Пирадов М.А., Танашян М.М., Максимова М.Ю. (ред.) Piradov M.A., Tanashyan M.M., Maksimova M.Yu. (eds.) [Stroke: modern technologies of diagnosis and treatment]. Мoscow, 2018. 360 p. doi: 10.24421/MP.2018.18.15909. (In Russ.)
  26. Lees K., Bluhmki E., von Kummer R. et al. Time to treatment with intravenous alteplase and outcome in stroke: an updated pooled analysis of ECASS, ATLANTIS, NINDS, and EPITHET trials. Lancet 2010; 375: 1695–1703. doi: 10.1016/S0140-6736(10)60491-6. PMID: 20472172.
  27. Sandercock P., Wardlaw J.M., Lindley R.I. et al. The benefits and harms of intravenous thrombolysis with recombinant tissue plasminogen activator within 6 h of acute ischaemic stroke (the Third International Stroke Trial [IST-3]): a randomised controlled trial [published correction appears in Lancet 2012; 380: 730]. Lancet 2012; 379: 2352–2363. doi: 10.1016/S0140-6736(12)60768-5. PMID: 22632908.
  28. Fonarow G.C., Zhao X., Smith E.E. et al. Door-to-needle times for tissue plasminogen activator administration and clinical outcomes in acute ischemic stroke before and after a quality improvement initiative. JAMA 2014; 311: 1632–1640. doi: 10.1001/jama.2014.3203. PMID: 24756513.
  29. Obviagele B., Reeves M.J., Nasiri M. et al. A simple risk index and thrombolytic treatment response in acute ischemic stroke. JAMA Neurol 2014; 71: 848–854. doi: 10.1001/jamaneurol.2014.689. PMID: 24798141.
  30. The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. Tissue plasminogen activator for acute ischemic stroke. N Engl J Med 1995; 333: 1581–1587. doi: 10.1056/NEJM199512143332401. PMID: 7477192.
  31. Hacke W., Kaste M., Bluhmki E. et al. Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. N Engl J Med 2008; 359: 1317–1322. doi: 10.1056/NEJMoa0804656. PMID: 18815396.
  32. Urbach H., Hartmann A., Pohl C. et al. Local intra-arterial thrombolysis in the carotid territory: does recanalization depend on the thromboembolus type? Neuroradiology 2002; 44: 695–699. doi: 10.1007/s00234-002-0762-6. PMID: 12185548.
  33. Bhatia R., Hill M.D., Shobha N. et al. Low rates of acute recanalization with intravenous recombinant tissue plasminogen activator in ischemic stroke: real-world experience and a call for action. Stroke 2010; 41: 2254–2258. doi: 10.1161/STROKEAHA.110.592535. PMID: 20829513.
  34. Broderick J.P., Palesch Y.Y., Demchuk A.M. et al. Endovascular therapy after intravenous t-PA versus t-PA alone for stroke. N Engl J Med 2013; 368: 893–903. doi: 10.1056/NEJMoa1214300. PMID: 23390923.
  35. Riedel C.H., Zimmermann P., Jensen-Kondering U. et al. The importance of size: successful recanalization by intravenous thrombolysis in acute anterior stroke depends on thrombus length. Stroke 2011; 42: 1775–1777. doi: 10.1161/STROKEAHA.110.609693. PMID: 21474810.
  36. Del Zoppo C.J., Poeck K., Pessin M.S. et al. Recombinant tissue plasminogen activator in acute thrombotic and embolic stroke. Ann Neurol 1992, 32: 78–86. doi: 10.1002/ana.410320113. PMID: 1642475.

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Copyright (c) 2019 Domashenko M.A., Maksimova M.Y., Tanashyan М.M.

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