Abstract
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.
Similar content being viewed by others
References
Saver JL (2006) Time is brain–quantified. Stroke 37:263–266
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 363:768–774
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 375:1695–1703
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 384:1929–1935
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 45:2734–2738
Weber J, Ebinger M, Audebert HJ (2015) Prehospital stroke care: telemedicine, thrombolysis and neuroprotection. Expert Rev Neurother 15:753–761
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 45:2555–2556
Grotta JC (2014) tPA for stroke: important progress in achieving faster treatment. JAMA 311:1615–1617
Tsivgoulis G, Kadlecová P, Kobayashi A et al (2015) Safety of statin pretreatment in intravenous thrombolysis for acute ischemic stroke. Stroke 46:2681–2684
Mikulík R, Kadlecová P, Czlonkowska A et al (2012) Factors influencing in-hospital delay in treatment with intravenous thrombolysis. Stroke 43:1578–1583
Alexandrov AV, Molina CA, Grotta JC et al (2004) Ultrasound-enhanced systemic thrombolysis for acute ischemic stroke. N Engl J Med 351:2170–2178
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 43:1524–1531
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 115:2660–2665
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 35:151–156
Tsivgoulis G, Katsanos AH, Sharma VK et al (2016) Statin pretreatment is associated with better outcomes in large artery atherosclerotic stroke. Neurology 86:1103–1111
Alexandrov AV, Nguyen HT, Rubiera M et al (2009) Prevalence and risk factors associated with reversed Robin Hood syndrome in acute ischemic stroke. Stroke 40:2738–2742
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 262:2135–2143
Saver JL, Gornbein J (2009) Treatment effects for which shift or binary analyses are advantageous in acute stroke trials. Neurology 72:1310–1315
Strbian D, Engelter S, Michel P et al (2012) Symptomatic intracranial hemorrhage after stroke thrombolysis: the SEDAN score. Ann Neurol 71:634–641
Strbian D, Meretoja A, Ahlhelm FJ et al (2012) Predicting outcome of IV thrombolysis-treated ischemic stroke patients: the DRAGON score. Neurology 78:427–432
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 135:128–139
Saver JL, Fonarow GC, Smith EE et al (2013) Time to treatment with intravenous tissue plasminogen activator and outcome from acute ischemic stroke. JAMA 309:2480–2488
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 123:750–758
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 44:2808–2813
Mullen MT, Branas CC, Kasner SE et al (2015) Optimization modeling to maximize population access to comprehensive stroke centers. Neurology 84:1196–1205
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 72:229–234
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 311:1622–1631
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 11:397–404
Parker SA, Bowry R, Wu TC et al (2015) Establishing the first mobile stroke unit in the United States. Stroke 46:1384–1391
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 67:2645–2655
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 6:493–497
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 260:635–639
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 215:431–434
Meretoja A, Strbian D, Mustanoja S, Tatlisumak T, Lindsberg PJ, Kaste M (2012) Reducing in-hospital delay to 20 minutes in stroke thrombolysis. Neurology 79:306–313
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 71:1155–1161
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 264:131–138
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflicts of interest
None.
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).
Electronic supplementary material
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Tsivgoulis, G., Katsanos, A.H., Kadlecová, P. et al. Intravenous thrombolysis for ischemic stroke in the golden hour: propensity-matched analysis from the SITS-EAST registry. J Neurol 264, 912–920 (2017). https://doi.org/10.1007/s00415-017-8461-8
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00415-017-8461-8