Iranian Journal of Neurology 2018. 17(1):31-37.

Prognostic factors in patients with acute ischemic stroke treated with intravenous tissue plasminogen activator: The first study among Iranian patients
Elyar Sadeghi-Hokmabadi, Mohammad Yazdchi, Mehdi Farhoudi, Homayoun Sadeghi, Aliakbar Taheraghdam, Reza Rikhtegar, Hannaneh Aliyar, Sahar Mohammadi-Fallah, Rogayyeh Asadi, Elham Mehdizadeh-Far, Neda Ghaemian


Background: Tissue plasminogen activator (tPA) has been long approved as an efficacious treatment in patients with acute ischemic stroke (AIS); however, due to some serious complications, particularly intracranial hemorrhage (ICH), many physicians are still reluctant to use it liberally. This study sought to find potential prognostic factors in patients with AIS treated with tPA.

Methods: A retrospective, hospital-bases observational study was conducted. Consecutively, a total of
132 patients with AIS treated with intravenous tPA, form June 2011 to July 2015 were enrolled. Inclusion and exclusion criteria were based on updated guidelines. Probable prognostic variables were examined separately in three distinct groups; the occurrence of ICH within 24 hours after treatment, poor 3-month outcome on the basis of modified Rankin Scale (mRS) and 3-month mortality.

Results: Patients were 83 men (62.9%) and
49 women (37.1%) with a median age of 66 years [interquartile range (IQR)of 55-72]. Any type of hemorrhage, symptomatic hemorrhage [based on the European Cooperative Acute Stroke Study III (ECASS III) definition] within 24 hours posttreatment, poor 3-month outcome (mRS 3-6), and 3-month mortality were documented in 10.6%, 4.5%, 53.2%, and 23.6% of patients, respectively. Increased baseline blood glucose was a significant but dependent predictor of hemorrhage within the first 24 hours posttreatment. Dependent predictors of a
3-month poor outcome were high age, the National Institutes of Health Stroke Scale (NIHSS) at baseline, decreased admitting glomerular filtration rate (GFR), and the presence of atrial fibrillation (AF) rhythm, and ICH within 24 hours posttreatment. Only age [Odds ratio (OR) adjusted 1.05] and initial NIHSS (OR adjusted 1.23), however, were recognized as the independent variables in this regard. The only independent predictor of 3-month mortality was the initial NIHSS (OR adjusted 1.18).

Conclusion: According to the findings of the present study, advanced age and high baseline NIHSS are two independent prognostic factors in patients with AIS treated with tPA.


Acute Ischemic Stroke; Tissue Plasminogen Activator; Outcome; Risk Factors

Full Text:



Furlan A, Higashida R, Wechsler L, Gent M, Rowley H, Kase C, et al. Intra-arterialprourokinase for acute ischemic stroke.The PROACT II study: A randomizedcontrolled trial. Prolyse in Acute CerebralThromboembolism. JAMA 1999;282(21): 2003-11.

Berkhemer OA, Fransen PS, Beumer D,van den Berg LA, Lingsma HF, Yoo AJ,et al. A randomized trial of intraarterialtreatment for acute ischemic stroke. NEngl J Med 2015; 372(1): 11-20.

Saver JL, Goyal M, Bonafe A, DienerHC, Levy EI, Pereira VM, et al. Stentretrieverthrombectomy after intravenoust-PA vs. t-PA alone in stroke. N Engl JMed 2015; 372(24): 2285-95.

Molina CA, Chamorro A, Rovira A, deMiquel A, Serena J, Roman LS, et al.REVASCAT: A randomized trial ofrevascularization with SOLITAIRE FRdevice vs. best medical therapy in thetreatment of acute stroke due to anteriorcirculation large vessel occlusionpresenting within eight-hours of symptomonset. Int J Stroke 2015; 10(4): 619-26.

Campbell BC, Mitchell PJ, Kleinig TJ,Dewey HM, Churilov L, Yassi N, et al.Endovascular therapy for ischemic strokewith perfusion-imaging selection. N EnglJ Med 2015; 372(11): 1009-18.

Goyal M, Demchuk AM, Menon BK,Eesa M, Rempel JL, Thornton J, et al.Randomized assessment of rapidendovascular treatment of ischemicstroke. N Engl J Med 2015; 372(11):1019-30.

Adams H, Adams R, Del ZG, GoldsteinLB. Guidelines for the early managementof patients with ischemic stroke: 2005

guidelines update a scientific statementfrom the Stroke Council of the AmericanHeart Association/American StrokeAssociation. Stroke 2005; 36(4): 916-23.

Adams HP Jr, Adams RJ, Brott T, delZoppo GJ, Furlan A, Goldstein LB, et al.Guidelines for the early management ofpatients with ischemic stroke: A scientificstatement from the Stroke Council of theAmerican Stroke Association. Stroke2003; 34(4): 1056-83.

Albers GW, Amarenco P, Easton JD,Sacco RL, Teal P. Antithrombotic andthrombolytic therapy for ischemic stroke:The Seventh ACCP Conference onAntithrombotic and ThrombolyticTherapy. Chest 2004; 126(3 Suppl):483S-512S.

Hosseini AA, Sobhani-Rad D,Ghandehari K, Benamer HT. Frequencyand clinical patterns of stroke in Iran-Systematic and critical review. BMCNeurol 2010; 10: 72.

Durai PJ, Padma V, Vijaya P, Sylaja PN,Murthy JM. Stroke and thrombolysis indeveloping countries. Int J Stroke 2007;2(1): 17-26.

Azarpazhooh MR, Etemadi MM, DonnanGA, Mokhber N, Majdi MR, Ghayour-Mobarhan M, et al. Excessive incidenceof stroke in Iran: Evidence from theMashhad Stroke Incidence Study (MSIS),a population-based study of stroke in theiddle East. Stroke 2010; 41(1): e3-e10.

Jauch EC, Saver JL, Adams HP Jr, BrunoA, Connors JJ, Demaerschalk BM, et al.Guidelines for the early management ofpatients with acute ischemic stroke: Aguideline for healthcare professionalsfrom the American HeartAssociation/American StrokeAssociation. Stroke 2013; 44(3): 870-947.

Hacke W, Kaste M, Bluhmki E, BrozmanM, Davalos A, Guidetti D, et al.Thrombolysis with alteplase 3 to 4.5hours after acute ischemic stroke. N EnglJ Med 2008; 359(13): 1317-29.

Albers GW, Bates VE, Clark WM, Bell R, Verro P, Hamilton SA. Intravenoustissue-type plasminogen activator fortreatment of acute stroke: The StandardTreatment with Alteplase to ReverseStroke (STARS) study. JAMA 2000;283(9): 1145-50.

Hacke W, Donnan G, Fieschi C, Kaste M,von Kummer R, Broderick JP, et al.Association of outcome with early stroketreatment: Pooled analysis ofATLANTIS, ECASS, and NINDS rt-PAstroke trials. Lancet 2004; 363(9411):768-74.

Hill MD, Buchan AM. Thrombolysis foracute ischemic stroke: Results of the Canadian Alteplase for StrokeEffectiveness Study. CMAJ 2005172(10): 1307-12.

Katzan IL, Furlan AJ, Lloyd LE, Frank JI, Harper DL, Hinchey JA, et al. Use oftissue-type plasminogen activator foracute ischemic stroke: The Clevelandarea experience. JAMA 2000; 283(9):1151-8.

Sauser-Zachrison K, Shen E, Ajani Z,Neil WP, Sangha N, Gould MK, et al.Emergency care of patients with acuteischemic stroke in the Kaiser Permanentesouthern California integrated healthsystem. Perm J 2016; 20(2): 10-3.

intravenous recombinant tissueplasminogen activator therapy for acuteischemic stroke in clinical practice: TheMulticenter rt-PA Stroke Survey.Circulation 2002; 105(14): 1679-85.

Tissue plasminogen activator for acuteischemic stroke. N Engl J Med 1995;333(24): 1581-7.

Lees KR, Bluhmki E, von Kummer R,Brott TG, Toni D, Grotta JC, et al. Timeto treatment with intravenous alteplaseand outcome in stroke: An updatedpooled analysis of ECASS, ATLANTIS,NINDS, and EPITHET trials. Lancet2010; 375(9727): 1695-703.

Mehrpour M, Aghaei M, Motamed MR.Safety and feasibility of intravenousthrombolytic therapy in Iranian patientswith acute ischemic stroke. Med J IslamRepub Iran 2013; 27(3): 113-8.

Nikkhah K, Avan A, Shoeibi A,Azarpazhooh A, Ghandehari K, Foerch C,et al. Gaps and hurdles deter againstfollowing stroke guidelines forthrombolytic therapy in Iran: Exploringthe problem. J Stroke Cerebrovasc Dis2015; 24(2): 408-15.

Cucchiara B, Kasner SE, Tanne D,Levine SR, Demchuk A, Messe SR, et al.Factors associated with intracerebralhemorrhage after thrombolytic therapyfor ischemic stroke: Pooled analysis ofplacebo data from the Stroke-AcuteIschemic NXY Treatment (SAINT) I and SAINT II Trials. Stroke 2009; 40(9):3067-72.

Lansberg MG, Albers GW, Wijman CA.Symptomatic intracerebral hemorrhagefollowing thrombolytic therapy for acuteischemic stroke: A review of the riskfactors. Cerebrovasc Dis 2007; 24(1): 1-10.

Larrue V, von Kummer RR, Muller A,Bluhmki E. Risk factors for severehemorrhagic transformation in ischemicstroke patients treated with recombinanttissue plasminogen activator: Asecondary analysis of the European-Australasian Acute Stroke Study (ECASSII). Stroke 2001; 32(2): 438-41.

Bravo Y, Marti-Fabregas J, Cocho D,Rodriguez-Yanez M, Castellanos M, de laOssa NP, et al. Influence of antiplateletpre-treatment on the risk of symptomaticintracranial haemorrhage afterintravenous thrombolysis. CerebrovascDis 2008; 26(2): 126-33.

Masrur S, Cox M, Bhatt DL, Smith EE,Ellrodt G, Fonarow GC, et al. Associationof acute and chronic hyperglycemia withacute ischemic stroke outcomes postthrombolysis:Findings from get with theguidelines-stroke. J Am Heart Assoc2015; 4(10): e002193.

Uyttenboogaart M, Koch MW, KoopmanK, Vroomen PC, De Keyser J, LuijckxGJ. Safety of antiplatelet therapy prior tointravenous thrombolysis in acuteischemic stroke. Arch Neurol 2008;65(5): 607-11.

Wahlgren N, Ahmed N, Eriksson N,Aichner F, Bluhmki E, Davalos A, et al.Multivariable analysis of outcomepredictors and adjustment of main

outcome results to baseline data profile inrandomized controlled trials: SafeImplementation of Thrombolysis inStroke-MOnitoring STudy (SITSMOST).Stroke 2008; 39(12): 3316-22.

Hao Z, Yang C, Liu M, Wu B. Renaldysfunction and thrombolytic therapy inpatients with acute ischemic stroke: Asystematic review and meta-analysis.Medicine (Baltimore) 2014; 93(28): e286

Gensicke H, Zinkstok SM, Roos YB,Seiffge DJ, Ringleb P, Artto V, et al. IVthrombolysis and renal function.Neurology 2013; 81(20): 1780-8.

Saposnik G, Gladstone D, Raptis R, ZhouL, Hart RG. Atrial fibrillation in ischemicstroke: Predicting response tothrombolysis and clinical outcomes.Stroke 2013; 44(1): 99-104.

Seet RC, Zhang Y, Wijdicks EF,Rabinstein AA. Relationship betweenchronic atrial fibrillation and worseoutcomes in stroke patients after intravenous thrombolysis. Arch Neurol2011; 68(11): 1454-8.

Saposnik G, Cote R, Phillips S, Gubitz G,Bayer N, Minuk J, et al. Stroke outcomein those over 80: A multicenter cohortstudy across Canada. Stroke 2008; 39(8):2310-7.

Aoki J, Kimura K, Sakamoto Y. Earlyadministration of tissue-plasminogenactivator improves the long-term clinicaloutcome at 5years after onset. J NeurolSci 2016; 362: 33-9.

Heuschmann PU, Kolominsky-Rabas PL,Roether J, Misselwitz B, Lowitzsch K,Heidrich J, et al. Predictors of in-hospitalmortality in patients with acute ischemicstroke treated with thrombolytic therapy.JAMA 2004; 292(15): 1831-8.

Strbian D, Meretoja A, Ahlhelm FJ,Pitkaniemi J, Lyrer P, Kaste M, et al.Predicting outcome of IV thrombolysistreatedischemic stroke patients: TheDRAGON score. Neurology 2012; 78(6):427-32.

del Rio-Espinola A, Fernandez-CadenasI, Giralt D, Quiroga A, Gutierrez-AgulloM, Quintana M, et al. A predictiveclinical-genetic model of tissueplasminogen activator response in acuteischemic stroke. Ann Neurol 2012; 72(5):716-29.

Reed SD, Cramer SC, Blough DK, MeyerK, Jarvik JG. Treatment with tissueplasminogen activator and inpatientmortality rates for patients with ischemicstroke treated in community hospitals.Stroke 2001; 32(8): 1832-40.


  • There are currently no refbacks.

Creative Commons Attribution-NonCommercial 3.0

This work is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License which allows users to read, copy, distribute and make derivative works for non-commercial purposes from the material, as long as the author of the original work is cited properly.