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Intravenous Thrombolysis for Acute Ischemic Stroke Associated to Extracranial Internal Carotid Artery Occlusion: The ICARO-2 Study

Paciaroni M.a · Agnelli G.a · Caso V.a · Pieroni A.b · Bovi P.c · Cappellari M.c · Zini A.d · Nichelli P.d · Inzitari D.e · Nesi M.e · Nencini P.e · Pezzini A.f · Padovani A.f · Tassinari T.g · Orlandi G.h · Chiti A.h · Gialdini G.h · Alberti A.a · Venti M.a · Acciarresi M.a · D’Amore C.a · Luda E.i · Tassi R.j · Martini G.j · Ferrarese C.k · Beretta S.k · Trentini C.k · Silvestrelli G.l · Lanari A.l · Previdi P.l · Ciccone A.l · DeLodovici M.L.m · Bono G.m · Galletti G.n · Marcheselli S.o · Del Sette M.p · Traverso E.p · Riva M.q · Silvestrini M.r · Cerqua R.r · Consoli D.s · Monaco S.t · Toni D.b
aStroke Unit and Division of Cardiovascular Medicine, University of Perugia, Perugia, bDepartment of Neurological Sciences, Sapienza University of Rome, Rome, cStroke Unit, Dipartimento di Scienze Neurologiche e della Visione, Azienda Ospedaliera-Universitaria, Verona, dStroke Unit, Neurology Clinic, Nuovo Ospedale Civile ‘S.Agostino – Estense’, University of Modena and Reggio Emilia, AUSL Modena, Modena, eDepartment of Neurological and Psychiatric Sciences, University of Florence, Florence, fDipartimento di Scienze Cliniche e Sperimentali, Clinica Neurologica, University of Brescia, Brescia, gStroke Unit – Department of Neurology, Santa Corona Hospital, Pietra Ligure, hClinica Neurologica – Azienda Ospedaliero-Universitaria, Pisa, iNeurology, Rivoli Hospital, Torino, jStroke Unit, AOU Senese, Siena, kSan Gerardo Hospital, University of Milano-Bicocca, Monza, lStroke Unit, Department of Neurology, Poma Hospital, Mantova, mStroke Unit, Neurology, Insubria University, Varese, nMorgagni-Pierantoni Hospital, Forlì, oStroke Unit, Humanitas Hospital, Milano, pStroke Unit, Department of Neurology, Sant’Andrea Hospital, La Spezia, qNeurology, Azienda Ospedaliera della Provincia di Lodi, Lodi, rDepartment of Neuroscience, Marche Polytechnic University, Ancona, sStroke Unit, Iazzolino Hospital, Vibo Valentia, and tStroke Unit, Ospedale Civico, Palermo, Italy Cerebrovasc Dis 2012;34:430–435 (DOI:10.1159/000345081)


Background and Purposes: In a case-control study in patients with acute ischemic stroke and extracranial internal carotid artery (eICA) occlusion, thrombolytic treatment was associated with increased mortality. The aim of this cohort study was to assess the efficacy and safety of thrombolysis in patients with eICA occlusion compared to those without eICA occlusion. Methods: Consecutive patients treated with intravenous tissue-type plasminogen activator within 4.5 h from symptom onset included in the Safe Implementation of Thrombolysis in Stroke – International Stroke Thrombolysis Registry (SITS-ISTR) in 20 Italian centres were analyzed. Acute carotid occlusion was diagnosed using ultrasound examination, angio-CT scan or angio-MRI. Since the SITS-ISTR database did not plan to report the site of vessel occlusion, each participating center provided the code of the patient with eICA occlusion. Patients were divided into 2 groups, those with and those without eICA occlusion. Main outcome measures were: death, disability (modified Rankin Scale, mRS, 3–6) and any intracranial bleeding at 3 months. Multiple logistic regression analysis was performed to reveal predictors for main outcomes. The following variables of interest were included in the analysis: presence of eICA occlusion, age, gender, diabetes mellitus, hyperlipidemia, atrial fibrillation, congestive heart failure, previous stroke, current smoking, antiplatelet treatment at stroke onset, baseline NIHSS score, baseline blood glucose, cholesterol and blood pressure, history of hypertension and stroke onset to treatment time. Results: A total of 1,761 patients without eICA occlusion and 137 with eICA occlusion were included in the study. At 3 months, 42 patients were lost to follow-up (3 with eICA occlusion). Death occurred in 30 (22.4%) patients with eICA occlusion and in 175 (10.2%) patients without (p < 0.0001). Death or disability at 3 months occurred in 91 of 134 patients with eICA occlusion (67.9%) compared with 654 of 1,722 patients without eICA occlusion (37.9%, p < 0.0001). No or minimal disability at 3 months (mRS 0–1) was reported in 25 (18.7%) patients with eICA occlusion and in 829 (48.2%) patients without (p < 0.0001). Any intracranial bleeding detected by CT or MRI at posttreatment imaging was seen in 16 (11.7%) patients with eICA occlusion and in 314 (17.8%) of those without (p = 0.09). The proportion of symptomatic intracerebral hemorrhage was 5.8% for patients with eICA occlusion and 8.0% for patients without (p = 0.16). At logistic regression analysis, eICA occlusion was associated with mortality (odds ratio, OR 5.7; 95% confidence interval, CI 2.9–11.1) and mortality or disability (OR 5.0; 95% CI 2.9–8.7) at 90 days. Conclusions: This cohort study in patients with acute ischemic stroke treated with thrombolysis showed an association between eICA occlusion and adverse outcome.


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