Journal of Neurology

, Volume 264, Issue 5, pp 912–920 | Cite as

Intravenous thrombolysis for ischemic stroke in the golden hour: propensity-matched analysis from the SITS-EAST registry

  • Georgios TsivgoulisEmail author
  • Aristeidis H. Katsanos
  • Pavla Kadlecová
  • Anna Czlonkowska
  • Adam Kobayashi
  • Miroslav Brozman
  • Viktor Švigelj
  • Laszlo Csiba
  • Klara Fekete
  • Janika Kõrv
  • Vida Demarin
  • Aleksandras Vilionskis
  • Dalius Jatuzis
  • Yakup Krespi
  • Chrissoula Liantinioti
  • Sotirios Giannopoulos
  • Robert Mikulik
Original Communication


As there are scarce data regarding the outcomes of acute ischemic stroke (AIS) patients treated with intravenous thrombolysis (IVT) within 60 min from symptom onset (“golden hour”), we sought to compare outcomes between AIS patients treated within [GH(+)] and outside [GH(−)] the “golden hour” by analyzing propensity score matched data from the SITS-EAST registry. Clinical recovery (CR) at 2 and 24 h was defined as a reduction of ≥10 points on NIHSS-score or a total NIHSS-score of ≤3 at 2 and 24 h, respectively. A relative reduction in NIHSS-score of ≥40% at 2 h was considered predictive of complete recanalization (CREC). Symptomatic intracranial hemorrhage (sICH) was defined using SITS-MOST criteria. Favorable functional outcome (FFO) was defined as a mRS-score of 0–1 at 3 months. Out of 19,077 IVT-treated AIS patients, 71 GH(+) patients were matched to 6882 GH(−) patients, with no differences in baseline characteristics (p > 0.1). GH(+) had higher rates of CR at 2 (31.0 vs. 12.4%; p < 0.001) and 24 h (41 vs. 27%; p = 0.010), CREC at 2 h (39 vs. 21%; p < 0.001) and FFO (46.5 vs. 34.0%; p = 0.028) at 3 months. The rates of sICH and 3-month mortality did not differ (p > 0.2) between the two groups. GH(+) was associated with 2-h CR (OR: 5.34; 95% CI 2.53–11.03) and CREC (OR: 2.38; 95% CI 1.38–4.09), 24-h CR (OR: 1.88; 95% CI 1.08–3.26) and 3-month FFO (OR: 2.02; 95% CI 1.15–3.54) in multivariable logistic regression models adjusting for potential confounders. In conclusion, AIS treated with IVT within the GH seems to have substantially higher odds of early neurological recovery, CREC, 3-month FFO and functional improvement.


Intravenous thrombolysis Acute ischemic stroke Golden hour Onset-to-treatment time Mobile stroke unit 


Compliance with ethical standards

Conflicts of interest


Ethical standards

The research documented in the submitted manuscript has been carried out in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and has been approved by the appropriate ethics committees of the participating institutions.

Sources of funding

Dr Georgios Tsivgoulis, Pavla Kadlecova and Robert Mikulik have been supported by the project no. LQ1605 from the National Program of Sustainability II (MEYS CR).

Supplementary material

415_2017_8461_MOESM1_ESM.docx (14 kb)
Supplementary material 1 (DOCX 14 kb)


  1. 1.
    Saver JL (2006) Time is brain–quantified. Stroke 37:263–266CrossRefPubMedGoogle Scholar
  2. 2.
    Hacke W, Donnan G, Fieschi C et al (2004) ATLANTIS Trials Investigators; ECASS Trials Investigators; NINDS rt-PA Study Group Investigators. Association of outcome with early stroke treatment: pooled analysis of ATLANTIS, ECASS, and NINDS rt-PA stroke trials. Lancet 363:768–774CrossRefPubMedGoogle Scholar
  3. 3.
    Lees KR, Bluhmki E, von Kummer R et al (2010) ECASS, ATLANTIS, NINDS and EPITHET rt-PA Study Group. Time to treatment with intravenous alteplase and outcome in stroke: an updated pooled analysis of ECASS, ATLANTIS, NINDS, and EPITHET trials. Lancet 375:1695–1703CrossRefPubMedGoogle Scholar
  4. 4.
    Emberson J, Lees KR, Lyden P et al (2014) Stroke Thrombolysis Trialists’ Collaborative Group. 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 384:1929–1935CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Muchada M, Rodriguez-Luna D, Pagola J et al (2014) Impact of time to treatment on tissue-type plasminogen activator-induced recanalization in acute ischemic stroke. Stroke 45:2734–2738CrossRefPubMedGoogle Scholar
  6. 6.
    Weber J, Ebinger M, Audebert HJ (2015) Prehospital stroke care: telemedicine, thrombolysis and neuroprotection. Expert Rev Neurother 15:753–761CrossRefPubMedGoogle Scholar
  7. 7.
    Tsivgoulis G, Alexandrov AV (2014) Does “time is brain” also mean “time is clot”? Time dependency of tissue-type plasminogen activator-induced recanalization in acute ischemic stroke. Stroke 45:2555–2556CrossRefPubMedGoogle Scholar
  8. 8.
    Grotta JC (2014) tPA for stroke: important progress in achieving faster treatment. JAMA 311:1615–1617CrossRefPubMedGoogle Scholar
  9. 9.
    Tsivgoulis G, Kadlecová P, Kobayashi A et al (2015) Safety of statin pretreatment in intravenous thrombolysis for acute ischemic stroke. Stroke 46:2681–2684CrossRefPubMedGoogle Scholar
  10. 10.
    Mikulík R, Kadlecová P, Czlonkowska A et al (2012) Factors influencing in-hospital delay in treatment with intravenous thrombolysis. Stroke 43:1578–1583CrossRefPubMedGoogle Scholar
  11. 11.
    Alexandrov AV, Molina CA, Grotta JC et al (2004) Ultrasound-enhanced systemic thrombolysis for acute ischemic stroke. N Engl J Med 351:2170–2178CrossRefPubMedGoogle Scholar
  12. 12.
    Mazya M, Egido JA, Ford GA et al (2012) Predicting the risk of symptomatic intracerebral hemorrhage in ischemic stroke treated with intravenous alteplase: safe Implementation of Treatments in Stroke (SITS) symptomatic intracerebral hemorrhage risk score. Stroke 43:1524–1531CrossRefPubMedGoogle Scholar
  13. 13.
    Mikulik R, Ribo M, Hill MD et al (2007) Accuracy of serial National Institutes of Health Stroke Scale scores to identify artery status in acute ischemic stroke. Circulation 115:2660–2665CrossRefPubMedGoogle Scholar
  14. 14.
    Molina CA, Alexandrov AV, Demchuk AM et al (2004) CLOTBUST Investigators. Improving the predictive accuracy of recanalization on stroke outcome in patients treated with tissue plasminogen activator. Stroke 35:151–156CrossRefPubMedGoogle Scholar
  15. 15.
    Tsivgoulis G, Katsanos AH, Sharma VK et al (2016) Statin pretreatment is associated with better outcomes in large artery atherosclerotic stroke. Neurology 86:1103–1111CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Alexandrov AV, Nguyen HT, Rubiera M et al (2009) Prevalence and risk factors associated with reversed Robin Hood syndrome in acute ischemic stroke. Stroke 40:2738–2742CrossRefPubMedGoogle Scholar
  17. 17.
    Tsivgoulis G, Zand R, Katsanos AH et al (2015) Safety and outcomes of intravenous thrombolysis in dissection-related ischemic stroke: an international multicenter study and comprehensive meta-analysis of reported case series. J Neurol 262:2135–2143CrossRefPubMedGoogle Scholar
  18. 18.
    Saver JL, Gornbein J (2009) Treatment effects for which shift or binary analyses are advantageous in acute stroke trials. Neurology 72:1310–1315CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Strbian D, Engelter S, Michel P et al (2012) Symptomatic intracranial hemorrhage after stroke thrombolysis: the SEDAN score. Ann Neurol 71:634–641CrossRefPubMedGoogle Scholar
  20. 20.
    Strbian D, Meretoja A, Ahlhelm FJ et al (2012) Predicting outcome of IV thrombolysis-treated ischemic stroke patients: the DRAGON score. Neurology 78:427–432CrossRefPubMedGoogle Scholar
  21. 21.
    Kim JT, Fonarow GC, Smith EE et al (2017) Treatment with tissue plasminogen activator in the golden hour and the shape of the 4.5-hour time-benefit curve in the National United States get with the guidelines-stroke population. Circulation 135:128–139CrossRefPubMedGoogle Scholar
  22. 22.
    Saver JL, Fonarow GC, Smith EE et al (2013) Time to treatment with intravenous tissue plasminogen activator and outcome from acute ischemic stroke. JAMA 309:2480–2488CrossRefPubMedGoogle Scholar
  23. 23.
    Fonarow GC, Smith EE, Saver JL et al (2011) Timeliness of tissue-type plasminogen activator therapy in acute ischemic stroke: patient characteristics, hospital factors, and outcomes associated with door-to-needle times within 60 min. Circulation 123:750–758CrossRefPubMedGoogle Scholar
  24. 24.
    Strbian D, Michel P, Ringleb P et al (2013) Relationship between onset-to-door time and door-to-thrombolysis time: a pooled analysis of 10 dedicated stroke centers. Stroke 44:2808–2813CrossRefPubMedGoogle Scholar
  25. 25.
    Mullen MT, Branas CC, Kasner SE et al (2015) Optimization modeling to maximize population access to comprehensive stroke centers. Neurology 84:1196–1205CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Rajan SS, Baraniuk S, Parker S, Wu TC, Bowry R, Grotta JC (2015) Implementing a mobile stroke unit program in the United States: why, how, and how much? JAMA Neurol 72:229–234CrossRefPubMedGoogle Scholar
  27. 27.
    Ebinger M, Winter B, Wendt M et al (2014) Effect of the use of ambulance-based thrombolysis on time to thrombolysis in acute ischemic stroke: a randomized clinical trial. JAMA 311:1622–1631CrossRefPubMedGoogle Scholar
  28. 28.
    Walter S, Kostopoulos P, Haass A, Keller I et al (2012) Diagnosis and treatment of patients with stroke in a mobile stroke unit versus in hospital: a randomised controlled trial. Lancet Neurol 11:397–404CrossRefPubMedGoogle Scholar
  29. 29.
    Parker SA, Bowry R, Wu TC et al (2015) Establishing the first mobile stroke unit in the United States. Stroke 46:1384–1391CrossRefPubMedGoogle Scholar
  30. 30.
    Mokin M, Snyder KV, Siddiqui AH, Levy EI, Hopkins LN (2016) Recent endovascular stroke trials and their impact on stroke systems of care. J Am Coll Cardiol 67:2645–2655CrossRefPubMedGoogle Scholar
  31. 31.
    Köhrmann M, Schellinger PD, Breuer L et al (2011) Avoiding in hospital delays and eliminating the three-hour effect in thrombolysis for stroke. Int J Stroke 6:493–497CrossRefPubMedGoogle Scholar
  32. 32.
    Casolla B, Bodenant M, Girot M et al (2013) Intra-hospital delays in stroke patients treated with rt-PA: impact of preadmission notification. J Neurol 260:635–639CrossRefPubMedGoogle Scholar
  33. 33.
    Vidale S, Arnaboldi M, Bezzi G et al (2016) Reducing time delays in the management of ischemic stroke patients in Northern Italy. Int J Cardiol 215:431–434CrossRefPubMedGoogle Scholar
  34. 34.
    Meretoja A, Strbian D, Mustanoja S, Tatlisumak T, Lindsberg PJ, Kaste M (2012) Reducing in-hospital delay to 20 minutes in stroke thrombolysis. Neurology 79:306–313CrossRefPubMedGoogle Scholar
  35. 35.
    Sauser K, Levine DA, Nickles AV, Reeves MJ (2014) Hospital variation in thrombolysis times among patients with acute ischemic stroke: the contributions of door-to-imaging time and imaging-to-needle time. JAMA Neurol 71:1155–1161CrossRefPubMedGoogle Scholar
  36. 36.
    Sommer P, Seyfang L, Posekany A et al (2017) Prehospital and intra-hospital time delays in posterior circulation stroke: results from the Austrian Stroke Unit Registry. J Neurol 264:131–138CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  • Georgios Tsivgoulis
    • 1
    • 2
    Email author
  • Aristeidis H. Katsanos
    • 1
    • 3
  • Pavla Kadlecová
    • 2
  • Anna Czlonkowska
    • 4
    • 5
  • Adam Kobayashi
    • 4
  • Miroslav Brozman
    • 6
  • Viktor Švigelj
    • 7
  • Laszlo Csiba
    • 8
  • Klara Fekete
    • 8
  • Janika Kõrv
    • 9
  • Vida Demarin
    • 10
  • Aleksandras Vilionskis
    • 11
  • Dalius Jatuzis
    • 12
  • Yakup Krespi
    • 13
  • Chrissoula Liantinioti
    • 1
  • Sotirios Giannopoulos
    • 3
  • Robert Mikulik
    • 2
    • 14
  1. 1.Second Department of Neurology, “Attikon” Hospital, School of MedicineUniversity of AthensAthensGreece
  2. 2.International Clinical Research Center and Neurology DepartmentSt. Anne’s HospitalBrnoCzech Republic
  3. 3.Department of NeurologyUniversity of IoanninaIoanninaGreece
  4. 4.Second Department of NeurologyInstitute of Psychiatry and NeurologyWarsawPoland
  5. 5.Department of Experimental and Clinical PharmacologyMedical University of WarsawWarsawPoland
  6. 6.Neurology DepartmentUniversity Hospital NitraNitraSlovakia
  7. 7.Department of Vascular Neurology and Neurological Intensive CareUniversity Medical Centre LjubljanaLjubljanaSlovenia
  8. 8.Department of Neurology, Medical and Health Science CenterUniversity of DebrecenDebrecenHungary
  9. 9.Department of Neurology and NeurosurgeryUniversity of TartuTartuEstonia
  10. 10.Department of NeurologySestre Milosrdnice University Hospital CentreZagrebCroatia
  11. 11.Department of Neurology and NeurosurgeryVilnius University and Republican Vilnius University HospitalVilniusLithuania
  12. 12.Department of Neurology and Neurosurgery, Center for NeurologyVilnius UniversityVilniusLithuania
  13. 13.Neurology Department and Stroke CenterMemorial Şişli HospitalIstanbulTurkey
  14. 14.Medical Faculty of Masaryk UniversityBrnoCzech Republic

Personalised recommendations