Intravenous thrombolysis or endovascular therapy for acute ischemic stroke associated with cervical internal carotid artery occlusion

the ICARO-3 study

Maurizio Paciaroni, Domenico Inzitari, Giancarlo Agnelli, Valeria Caso, Clotilde Balucani, James C. Grotta, Amrou Sarraj, Sohn Sung-Il, Angel Chamorro, Xabier Urra, Didier Leys, Hilde Henon, Charlotte Cordonnier, Nelly Dequatre, Pierre Aguettaz, Andrea Alberti, Michele Venti, Monica Acciarresi, Cataldo D’Amore, Andrea Zini & 54 others Stefano Vallone, Maria Luisa Dell’Acqua, Federico Menetti, Patrizia Nencini, Salvatore Mangiafico, Kristian Barlinn, Jessica Kepplinger, Ulf Bodechtel, Johannes Gerber, Paolo Bovi, Manuel Cappellari, Italo Linfante, Guilherme Dabus, Simona Marcheselli, Alessandro Pezzini, Alessandro Padovani, Andrei Alexandrov, Reza Bavarsad Shahripour, Maria Sessa, Giacomo Giacalone, Giorgio Silvestrelli, Alessia Lanari, Alfonso Ciccone, Alessandro De Vito, Cristiano Azzini, Andrea Saletti, Enrico Fainardi, Giovanni Orlandi, Alberto Chiti, Gino Gialdini, Mauro Silvestrini, Carlo Ferrarese, Simone Beretta, Rossana Tassi, Giuseppe Martini, Georgios Tsivgoulis, Spyros N. Vasdekis, Domenico Consoli, Antonio Baldi, Sebastiano D’Anna, Emilio Luda, Ferdinando Varbella, Giampiero Galletti, Paolo Invernizzi, Edoardo Donati, Maria Luisa De Lodovici, Giorgio Bono, Francesco Corea, Massimo Del Sette, Serena Monaco, Maurizio Riva, Tiziana Tassinari, Umberto Scoditti, Danilo Toni

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

The aim of the ICARO-3 study was to evaluate whether intra-arterial treatment, compared to intravenous thrombolysis, increases the rate of favourable functional outcome at 3 months in acute ischemic stroke and extracranial ICA occlusion. ICARO-3 was a non-randomized therapeutic trial that performed a non-blind assessment of outcomes using retrospective data collected prospectively from 37 centres in 7 countries. Patients treated with endovascular treatment within 6 h from stroke onset (cases) were matched with patients treated with intravenous thrombolysis within 4.5 h from symptom onset (controls). Patients receiving either intravenous or endovascular therapy were included among the cases. The efficacy outcome was disability at 90 days assessed by the modified Rankin Scale (mRS), dichotomized as favourable (score of 0–2) or unfavourable (score of 3–6). Safety outcomes were death and any intracranial bleeding. Included in the analysis were 324 cases and 324 controls: 105 cases (32.4 %) had a favourable outcome as compared with 89 controls (27.4 %) [adjusted odds ratio (OR) 1.25, 95 % confidence interval (CI) 0.88–1.79, p = 0.1]. In the adjusted analysis, treatment with intra-arterial procedures was significantly associated with a reduction of mortality (OR 0.61, 95 % CI 0.40–0.93, p = 0.022). The rates of patients with severe disability or death (mRS 5–6) were similar in cases and controls (30.5 versus 32.4 %, p = 0.67). For the ordinal analysis, adjusted for age, sex, NIHSS, presence of diabetes mellitus and atrial fibrillation, the common odds ratio was 1.15 (95 % IC 0.86–1.54), p = 0.33. There were more cases of intracranial bleeding (37.0 versus 17.3 %, p = 0.0001) in the intra-arterial procedure group than in the intravenous group. After the exclusion of the 135 cases treated with the combination of I.V. thrombolysis and I.A. procedures, 67/189 of those treated with I.A. procedures (35.3 %) had a favourable outcome, compared to 89/324 of those treated with I.V. thrombolysis (27.4 %) (adjusted OR 1.75, 95 % CI 1.00–3.03, p = 0.05). Endovascular treatment of patients with acute ICA occlusion did not result in a better functional outcome than treatment with intravenous thrombolysis, but was associated with a higher rate of intracranial bleeding. Overall mortality was significantly reduced in patients treated with endovascular treatment but the rates of patients with severe disability or death were similar. When excluding all patients treated with the combination of I.V. thrombolysis and I.A. procedures, a potential benefit of I.A. treatment alone compared to I.V. thrombolysis was observed.

Original languageEnglish (US)
Pages (from-to)459-468
Number of pages10
JournalJournal of Neurology
Volume262
Issue number2
DOIs
StatePublished - Jan 1 2015

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Internal Carotid Artery
Stroke
Odds Ratio
Confidence Intervals
Therapeutics
Hemorrhage
Mortality
Atrial Fibrillation
Diabetes Mellitus
Outcome Assessment (Health Care)
Safety

All Science Journal Classification (ASJC) codes

  • Neurology
  • Clinical Neurology

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Intravenous thrombolysis or endovascular therapy for acute ischemic stroke associated with cervical internal carotid artery occlusion : the ICARO-3 study. / Paciaroni, Maurizio; Inzitari, Domenico; Agnelli, Giancarlo; Caso, Valeria; Balucani, Clotilde; Grotta, James C.; Sarraj, Amrou; Sung-Il, Sohn; Chamorro, Angel; Urra, Xabier; Leys, Didier; Henon, Hilde; Cordonnier, Charlotte; Dequatre, Nelly; Aguettaz, Pierre; Alberti, Andrea; Venti, Michele; Acciarresi, Monica; D’Amore, Cataldo; Zini, Andrea; Vallone, Stefano; Dell’Acqua, Maria Luisa; Menetti, Federico; Nencini, Patrizia; Mangiafico, Salvatore; Barlinn, Kristian; Kepplinger, Jessica; Bodechtel, Ulf; Gerber, Johannes; Bovi, Paolo; Cappellari, Manuel; Linfante, Italo; Dabus, Guilherme; Marcheselli, Simona; Pezzini, Alessandro; Padovani, Alessandro; Alexandrov, Andrei; Shahripour, Reza Bavarsad; Sessa, Maria; Giacalone, Giacomo; Silvestrelli, Giorgio; Lanari, Alessia; Ciccone, Alfonso; De Vito, Alessandro; Azzini, Cristiano; Saletti, Andrea; Fainardi, Enrico; Orlandi, Giovanni; Chiti, Alberto; Gialdini, Gino; Silvestrini, Mauro; Ferrarese, Carlo; Beretta, Simone; Tassi, Rossana; Martini, Giuseppe; Tsivgoulis, Georgios; Vasdekis, Spyros N.; Consoli, Domenico; Baldi, Antonio; D’Anna, Sebastiano; Luda, Emilio; Varbella, Ferdinando; Galletti, Giampiero; Invernizzi, Paolo; Donati, Edoardo; De Lodovici, Maria Luisa; Bono, Giorgio; Corea, Francesco; Sette, Massimo Del; Monaco, Serena; Riva, Maurizio; Tassinari, Tiziana; Scoditti, Umberto; Toni, Danilo.

In: Journal of Neurology, Vol. 262, No. 2, 01.01.2015, p. 459-468.

Research output: Contribution to journalArticle

Paciaroni, M, Inzitari, D, Agnelli, G, Caso, V, Balucani, C, Grotta, JC, Sarraj, A, Sung-Il, S, Chamorro, A, Urra, X, Leys, D, Henon, H, Cordonnier, C, Dequatre, N, Aguettaz, P, Alberti, A, Venti, M, Acciarresi, M, D’Amore, C, Zini, A, Vallone, S, Dell’Acqua, ML, Menetti, F, Nencini, P, Mangiafico, S, Barlinn, K, Kepplinger, J, Bodechtel, U, Gerber, J, Bovi, P, Cappellari, M, Linfante, I, Dabus, G, Marcheselli, S, Pezzini, A, Padovani, A, Alexandrov, A, Shahripour, RB, Sessa, M, Giacalone, G, Silvestrelli, G, Lanari, A, Ciccone, A, De Vito, A, Azzini, C, Saletti, A, Fainardi, E, Orlandi, G, Chiti, A, Gialdini, G, Silvestrini, M, Ferrarese, C, Beretta, S, Tassi, R, Martini, G, Tsivgoulis, G, Vasdekis, SN, Consoli, D, Baldi, A, D’Anna, S, Luda, E, Varbella, F, Galletti, G, Invernizzi, P, Donati, E, De Lodovici, ML, Bono, G, Corea, F, Sette, MD, Monaco, S, Riva, M, Tassinari, T, Scoditti, U & Toni, D 2015, 'Intravenous thrombolysis or endovascular therapy for acute ischemic stroke associated with cervical internal carotid artery occlusion: the ICARO-3 study', Journal of Neurology, vol. 262, no. 2, pp. 459-468. https://doi.org/10.1007/s00415-014-7550-1
Paciaroni, Maurizio ; Inzitari, Domenico ; Agnelli, Giancarlo ; Caso, Valeria ; Balucani, Clotilde ; Grotta, James C. ; Sarraj, Amrou ; Sung-Il, Sohn ; Chamorro, Angel ; Urra, Xabier ; Leys, Didier ; Henon, Hilde ; Cordonnier, Charlotte ; Dequatre, Nelly ; Aguettaz, Pierre ; Alberti, Andrea ; Venti, Michele ; Acciarresi, Monica ; D’Amore, Cataldo ; Zini, Andrea ; Vallone, Stefano ; Dell’Acqua, Maria Luisa ; Menetti, Federico ; Nencini, Patrizia ; Mangiafico, Salvatore ; Barlinn, Kristian ; Kepplinger, Jessica ; Bodechtel, Ulf ; Gerber, Johannes ; Bovi, Paolo ; Cappellari, Manuel ; Linfante, Italo ; Dabus, Guilherme ; Marcheselli, Simona ; Pezzini, Alessandro ; Padovani, Alessandro ; Alexandrov, Andrei ; Shahripour, Reza Bavarsad ; Sessa, Maria ; Giacalone, Giacomo ; Silvestrelli, Giorgio ; Lanari, Alessia ; Ciccone, Alfonso ; De Vito, Alessandro ; Azzini, Cristiano ; Saletti, Andrea ; Fainardi, Enrico ; Orlandi, Giovanni ; Chiti, Alberto ; Gialdini, Gino ; Silvestrini, Mauro ; Ferrarese, Carlo ; Beretta, Simone ; Tassi, Rossana ; Martini, Giuseppe ; Tsivgoulis, Georgios ; Vasdekis, Spyros N. ; Consoli, Domenico ; Baldi, Antonio ; D’Anna, Sebastiano ; Luda, Emilio ; Varbella, Ferdinando ; Galletti, Giampiero ; Invernizzi, Paolo ; Donati, Edoardo ; De Lodovici, Maria Luisa ; Bono, Giorgio ; Corea, Francesco ; Sette, Massimo Del ; Monaco, Serena ; Riva, Maurizio ; Tassinari, Tiziana ; Scoditti, Umberto ; Toni, Danilo. / Intravenous thrombolysis or endovascular therapy for acute ischemic stroke associated with cervical internal carotid artery occlusion : the ICARO-3 study. In: Journal of Neurology. 2015 ; Vol. 262, No. 2. pp. 459-468.
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abstract = "The aim of the ICARO-3 study was to evaluate whether intra-arterial treatment, compared to intravenous thrombolysis, increases the rate of favourable functional outcome at 3 months in acute ischemic stroke and extracranial ICA occlusion. ICARO-3 was a non-randomized therapeutic trial that performed a non-blind assessment of outcomes using retrospective data collected prospectively from 37 centres in 7 countries. Patients treated with endovascular treatment within 6 h from stroke onset (cases) were matched with patients treated with intravenous thrombolysis within 4.5 h from symptom onset (controls). Patients receiving either intravenous or endovascular therapy were included among the cases. The efficacy outcome was disability at 90 days assessed by the modified Rankin Scale (mRS), dichotomized as favourable (score of 0–2) or unfavourable (score of 3–6). Safety outcomes were death and any intracranial bleeding. Included in the analysis were 324 cases and 324 controls: 105 cases (32.4 {\%}) had a favourable outcome as compared with 89 controls (27.4 {\%}) [adjusted odds ratio (OR) 1.25, 95 {\%} confidence interval (CI) 0.88–1.79, p = 0.1]. In the adjusted analysis, treatment with intra-arterial procedures was significantly associated with a reduction of mortality (OR 0.61, 95 {\%} CI 0.40–0.93, p = 0.022). The rates of patients with severe disability or death (mRS 5–6) were similar in cases and controls (30.5 versus 32.4 {\%}, p = 0.67). For the ordinal analysis, adjusted for age, sex, NIHSS, presence of diabetes mellitus and atrial fibrillation, the common odds ratio was 1.15 (95 {\%} IC 0.86–1.54), p = 0.33. There were more cases of intracranial bleeding (37.0 versus 17.3 {\%}, p = 0.0001) in the intra-arterial procedure group than in the intravenous group. After the exclusion of the 135 cases treated with the combination of I.V. thrombolysis and I.A. procedures, 67/189 of those treated with I.A. procedures (35.3 {\%}) had a favourable outcome, compared to 89/324 of those treated with I.V. thrombolysis (27.4 {\%}) (adjusted OR 1.75, 95 {\%} CI 1.00–3.03, p = 0.05). Endovascular treatment of patients with acute ICA occlusion did not result in a better functional outcome than treatment with intravenous thrombolysis, but was associated with a higher rate of intracranial bleeding. Overall mortality was significantly reduced in patients treated with endovascular treatment but the rates of patients with severe disability or death were similar. When excluding all patients treated with the combination of I.V. thrombolysis and I.A. procedures, a potential benefit of I.A. treatment alone compared to I.V. thrombolysis was observed.",
author = "Maurizio Paciaroni and Domenico Inzitari and Giancarlo Agnelli and Valeria Caso and Clotilde Balucani and Grotta, {James C.} and Amrou Sarraj and Sohn Sung-Il and Angel Chamorro and Xabier Urra and Didier Leys and Hilde Henon and Charlotte Cordonnier and Nelly Dequatre and Pierre Aguettaz and Andrea Alberti and Michele Venti and Monica Acciarresi and Cataldo D’Amore and Andrea Zini and Stefano Vallone and Dell’Acqua, {Maria Luisa} and Federico Menetti and Patrizia Nencini and Salvatore Mangiafico and Kristian Barlinn and Jessica Kepplinger and Ulf Bodechtel and Johannes Gerber and Paolo Bovi and Manuel Cappellari and Italo Linfante and Guilherme Dabus and Simona Marcheselli and Alessandro Pezzini and Alessandro Padovani and Andrei Alexandrov and Shahripour, {Reza Bavarsad} and Maria Sessa and Giacomo Giacalone and Giorgio Silvestrelli and Alessia Lanari and Alfonso Ciccone and {De Vito}, Alessandro and Cristiano Azzini and Andrea Saletti and Enrico Fainardi and Giovanni Orlandi and Alberto Chiti and Gino Gialdini and Mauro Silvestrini and Carlo Ferrarese and Simone Beretta and Rossana Tassi and Giuseppe Martini and Georgios Tsivgoulis and Vasdekis, {Spyros N.} and Domenico Consoli and Antonio Baldi and Sebastiano D’Anna and Emilio Luda and Ferdinando Varbella and Giampiero Galletti and Paolo Invernizzi and Edoardo Donati and {De Lodovici}, {Maria Luisa} and Giorgio Bono and Francesco Corea and Sette, {Massimo Del} and Serena Monaco and Maurizio Riva and Tiziana Tassinari and Umberto Scoditti and Danilo Toni",
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TY - JOUR

T1 - Intravenous thrombolysis or endovascular therapy for acute ischemic stroke associated with cervical internal carotid artery occlusion

T2 - the ICARO-3 study

AU - Paciaroni, Maurizio

AU - Inzitari, Domenico

AU - Agnelli, Giancarlo

AU - Caso, Valeria

AU - Balucani, Clotilde

AU - Grotta, James C.

AU - Sarraj, Amrou

AU - Sung-Il, Sohn

AU - Chamorro, Angel

AU - Urra, Xabier

AU - Leys, Didier

AU - Henon, Hilde

AU - Cordonnier, Charlotte

AU - Dequatre, Nelly

AU - Aguettaz, Pierre

AU - Alberti, Andrea

AU - Venti, Michele

AU - Acciarresi, Monica

AU - D’Amore, Cataldo

AU - Zini, Andrea

AU - Vallone, Stefano

AU - Dell’Acqua, Maria Luisa

AU - Menetti, Federico

AU - Nencini, Patrizia

AU - Mangiafico, Salvatore

AU - Barlinn, Kristian

AU - Kepplinger, Jessica

AU - Bodechtel, Ulf

AU - Gerber, Johannes

AU - Bovi, Paolo

AU - Cappellari, Manuel

AU - Linfante, Italo

AU - Dabus, Guilherme

AU - Marcheselli, Simona

AU - Pezzini, Alessandro

AU - Padovani, Alessandro

AU - Alexandrov, Andrei

AU - Shahripour, Reza Bavarsad

AU - Sessa, Maria

AU - Giacalone, Giacomo

AU - Silvestrelli, Giorgio

AU - Lanari, Alessia

AU - Ciccone, Alfonso

AU - De Vito, Alessandro

AU - Azzini, Cristiano

AU - Saletti, Andrea

AU - Fainardi, Enrico

AU - Orlandi, Giovanni

AU - Chiti, Alberto

AU - Gialdini, Gino

AU - Silvestrini, Mauro

AU - Ferrarese, Carlo

AU - Beretta, Simone

AU - Tassi, Rossana

AU - Martini, Giuseppe

AU - Tsivgoulis, Georgios

AU - Vasdekis, Spyros N.

AU - Consoli, Domenico

AU - Baldi, Antonio

AU - D’Anna, Sebastiano

AU - Luda, Emilio

AU - Varbella, Ferdinando

AU - Galletti, Giampiero

AU - Invernizzi, Paolo

AU - Donati, Edoardo

AU - De Lodovici, Maria Luisa

AU - Bono, Giorgio

AU - Corea, Francesco

AU - Sette, Massimo Del

AU - Monaco, Serena

AU - Riva, Maurizio

AU - Tassinari, Tiziana

AU - Scoditti, Umberto

AU - Toni, Danilo

PY - 2015/1/1

Y1 - 2015/1/1

N2 - The aim of the ICARO-3 study was to evaluate whether intra-arterial treatment, compared to intravenous thrombolysis, increases the rate of favourable functional outcome at 3 months in acute ischemic stroke and extracranial ICA occlusion. ICARO-3 was a non-randomized therapeutic trial that performed a non-blind assessment of outcomes using retrospective data collected prospectively from 37 centres in 7 countries. Patients treated with endovascular treatment within 6 h from stroke onset (cases) were matched with patients treated with intravenous thrombolysis within 4.5 h from symptom onset (controls). Patients receiving either intravenous or endovascular therapy were included among the cases. The efficacy outcome was disability at 90 days assessed by the modified Rankin Scale (mRS), dichotomized as favourable (score of 0–2) or unfavourable (score of 3–6). Safety outcomes were death and any intracranial bleeding. Included in the analysis were 324 cases and 324 controls: 105 cases (32.4 %) had a favourable outcome as compared with 89 controls (27.4 %) [adjusted odds ratio (OR) 1.25, 95 % confidence interval (CI) 0.88–1.79, p = 0.1]. In the adjusted analysis, treatment with intra-arterial procedures was significantly associated with a reduction of mortality (OR 0.61, 95 % CI 0.40–0.93, p = 0.022). The rates of patients with severe disability or death (mRS 5–6) were similar in cases and controls (30.5 versus 32.4 %, p = 0.67). For the ordinal analysis, adjusted for age, sex, NIHSS, presence of diabetes mellitus and atrial fibrillation, the common odds ratio was 1.15 (95 % IC 0.86–1.54), p = 0.33. There were more cases of intracranial bleeding (37.0 versus 17.3 %, p = 0.0001) in the intra-arterial procedure group than in the intravenous group. After the exclusion of the 135 cases treated with the combination of I.V. thrombolysis and I.A. procedures, 67/189 of those treated with I.A. procedures (35.3 %) had a favourable outcome, compared to 89/324 of those treated with I.V. thrombolysis (27.4 %) (adjusted OR 1.75, 95 % CI 1.00–3.03, p = 0.05). Endovascular treatment of patients with acute ICA occlusion did not result in a better functional outcome than treatment with intravenous thrombolysis, but was associated with a higher rate of intracranial bleeding. Overall mortality was significantly reduced in patients treated with endovascular treatment but the rates of patients with severe disability or death were similar. When excluding all patients treated with the combination of I.V. thrombolysis and I.A. procedures, a potential benefit of I.A. treatment alone compared to I.V. thrombolysis was observed.

AB - The aim of the ICARO-3 study was to evaluate whether intra-arterial treatment, compared to intravenous thrombolysis, increases the rate of favourable functional outcome at 3 months in acute ischemic stroke and extracranial ICA occlusion. ICARO-3 was a non-randomized therapeutic trial that performed a non-blind assessment of outcomes using retrospective data collected prospectively from 37 centres in 7 countries. Patients treated with endovascular treatment within 6 h from stroke onset (cases) were matched with patients treated with intravenous thrombolysis within 4.5 h from symptom onset (controls). Patients receiving either intravenous or endovascular therapy were included among the cases. The efficacy outcome was disability at 90 days assessed by the modified Rankin Scale (mRS), dichotomized as favourable (score of 0–2) or unfavourable (score of 3–6). Safety outcomes were death and any intracranial bleeding. Included in the analysis were 324 cases and 324 controls: 105 cases (32.4 %) had a favourable outcome as compared with 89 controls (27.4 %) [adjusted odds ratio (OR) 1.25, 95 % confidence interval (CI) 0.88–1.79, p = 0.1]. In the adjusted analysis, treatment with intra-arterial procedures was significantly associated with a reduction of mortality (OR 0.61, 95 % CI 0.40–0.93, p = 0.022). The rates of patients with severe disability or death (mRS 5–6) were similar in cases and controls (30.5 versus 32.4 %, p = 0.67). For the ordinal analysis, adjusted for age, sex, NIHSS, presence of diabetes mellitus and atrial fibrillation, the common odds ratio was 1.15 (95 % IC 0.86–1.54), p = 0.33. There were more cases of intracranial bleeding (37.0 versus 17.3 %, p = 0.0001) in the intra-arterial procedure group than in the intravenous group. After the exclusion of the 135 cases treated with the combination of I.V. thrombolysis and I.A. procedures, 67/189 of those treated with I.A. procedures (35.3 %) had a favourable outcome, compared to 89/324 of those treated with I.V. thrombolysis (27.4 %) (adjusted OR 1.75, 95 % CI 1.00–3.03, p = 0.05). Endovascular treatment of patients with acute ICA occlusion did not result in a better functional outcome than treatment with intravenous thrombolysis, but was associated with a higher rate of intracranial bleeding. Overall mortality was significantly reduced in patients treated with endovascular treatment but the rates of patients with severe disability or death were similar. When excluding all patients treated with the combination of I.V. thrombolysis and I.A. procedures, a potential benefit of I.A. treatment alone compared to I.V. thrombolysis was observed.

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