Journal of Neurology

, Volume 262, Issue 2, pp 459–468 | Cite as

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
  • 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 V. 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
Original Communication

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.

Keywords

Acute stroke Thrombolysis Endovascular procedures 

Notes

Conflicts of interest

The study was conducted under the nonfinancial auspices of the Italian Stroke Association. M.P. received honoraria as a member of the speaker bureau of Sanofi-Aventis. G.A. received honoraria as a member of the speaker bureau of Boehringer Ingelheim and Bayer. D.L. has had consultancy roles for and has contributed to advisory boards, steering committees, and adjudication committees for Sanofi-Aventis, Servier, Boehringer Ingelheim, AstraZeneca, Novo-Nordisk, Allergan, Bayer, Ebewe, CoLucid Pharma, Brainsgate, Photothera, Lundbeck, and GSK, fees for which were paid toward research at ADRINORD (Association pour le De´veloppement de la Recherche et de l’Innovation dans le Nord-Pas de Calais) or the research account of the hospital (de´le´gation a` la recherche du CHU de Lille). He was reimbursed for travel or accommodation expenses needed for the participation on these boards and committees. He was associate editor of the Journal of Neurology, Neurosurgery and Psychiatry from 2004 to 2010. GT has been supported by European Regional Development Fund—Project FNUSA-ICRC (N. CZ.1.05/1.1.00/02.0123). D.T. was paid for expert testimony by Boehringer Ingelheim, Pfizer, and Sanofi-Aventis. The other authors have nothing to disclose.

Ethical standards

The study has been approved by the appropriate ethics committee and have therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. All persons gave their informed consent prior to their inclusion in the study.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Maurizio Paciaroni
    • 1
  • Domenico Inzitari
    • 2
  • Giancarlo Agnelli
    • 1
  • Valeria Caso
    • 1
  • Clotilde Balucani
    • 3
  • James C. Grotta
    • 3
  • Amrou Sarraj
    • 3
  • Sohn Sung-Il
    • 4
  • Angel Chamorro
    • 5
  • Xabier Urra
    • 5
  • Didier Leys
    • 6
  • Hilde Henon
    • 6
  • Charlotte Cordonnier
    • 6
  • Nelly Dequatre
    • 6
  • Pierre Aguettaz
    • 6
  • Andrea Alberti
    • 1
  • Michele Venti
    • 1
  • Monica Acciarresi
    • 1
  • Cataldo D’Amore
    • 1
  • Andrea Zini
    • 7
  • Stefano Vallone
    • 8
  • Maria Luisa Dell’Acqua
    • 7
  • Federico Menetti
    • 8
  • Patrizia Nencini
    • 2
  • Salvatore Mangiafico
    • 2
  • Kristian Barlinn
    • 9
  • Jessica Kepplinger
    • 9
  • Ulf Bodechtel
    • 9
  • Johannes Gerber
    • 9
  • Paolo Bovi
    • 10
  • Manuel Cappellari
    • 10
  • Italo Linfante
    • 11
  • Guilherme Dabus
    • 11
  • Simona Marcheselli
    • 12
  • Alessandro Pezzini
    • 13
  • Alessandro Padovani
    • 13
  • Andrei V. Alexandrov
    • 14
  • Reza Bavarsad Shahripour
    • 14
  • Maria Sessa
    • 15
  • Giacomo Giacalone
    • 15
  • Giorgio Silvestrelli
    • 16
  • Alessia Lanari
    • 16
  • Alfonso Ciccone
    • 16
  • Alessandro De Vito
    • 17
  • Cristiano Azzini
    • 17
  • Andrea Saletti
    • 18
  • Enrico Fainardi
    • 18
  • Giovanni Orlandi
    • 19
  • Alberto Chiti
    • 19
  • Gino Gialdini
    • 19
  • Mauro Silvestrini
    • 20
  • Carlo Ferrarese
    • 21
  • Simone Beretta
    • 21
  • Rossana Tassi
    • 22
  • Giuseppe Martini
    • 22
  • Georgios Tsivgoulis
    • 23
    • 24
    • 25
  • Spyros N. Vasdekis
    • 26
  • Domenico Consoli
    • 27
  • Antonio Baldi
    • 28
  • Sebastiano D’Anna
    • 28
  • Emilio Luda
    • 29
  • Ferdinando Varbella
    • 30
  • Giampiero Galletti
    • 31
  • Paolo Invernizzi
    • 32
  • Edoardo Donati
    • 32
  • Maria Luisa De Lodovici
    • 33
  • Giorgio Bono
    • 33
  • Francesco Corea
    • 34
  • Massimo Del Sette
    • 35
  • Serena Monaco
    • 36
  • Maurizio Riva
    • 37
  • Tiziana Tassinari
    • 38
  • Umberto Scoditti
    • 39
  • Danilo Toni
    • 40
  1. 1.Stroke Unit and Division of Internal and Cardiovascular Medicine, Santa Maria della Misericordia HospitalUniversity of PerugiaPerugiaItaly
  2. 2.Department of Neurological and Psychiatric SciencesUniversity of FlorenceFlorenceItaly
  3. 3.Department of NeurologyUniversity of Texas Medical SchoolHoustonUSA
  4. 4.Department of NeurologyKeimyung University School of MedicineDaeguSouth Korea
  5. 5.Functional Unit of Cerebrovascular Diseases, Hospital ClinicBarcelonaSpain
  6. 6.Department of NeurologyUniversity of Lille Nord de FranceLilleFrance
  7. 7.Stroke Unit, Neurology Clinic, Nuovo Ospedale Civile “S.Agostino-Estense”University of Modena e Reggio Emilia, AUSL ModenaAUSL ModenaItaly
  8. 8.Neuroradiology Unit, Department of Neuroscience, Nuovo Ospedale Civile “S.Agostino-Estense”University of Modena e Reggio Emilia, AUSL ModenaAUSL ModenaItaly
  9. 9.Department of NeurologyDresden University Stroke CenterDresdenGermany
  10. 10.SSO Stroke Unit, UO Neurologia dO, DAI di Neuroscienze, AOUI VeronaAOUI VeronaItaly
  11. 11.Endovascular Neurosurgery, Interventional Neuroradiology, Baptist Cardiac and Vascular Institute, Herbert Wertheim College of MedicineFlorida International UniversityMiamiUSA
  12. 12.Stroke Unit, Humanitas HospitalMilanItaly
  13. 13.Dipartimento di Scienze Mediche e Chirurgiche, Clinica NeurologicaUniversity of BresciaBresciaItaly
  14. 14.Comprehesive Stroke CenterUniversity of BirminghamAlabamaUSA
  15. 15.Stroke Unit, Department of NeurologySan Raffaele HospitalMilanItaly
  16. 16.Department of NeurologyPoma HospitalMantuaItaly
  17. 17.Stroke Unit, Division of Neurology, Department of Neuroscience and RehabilitationAzienda Ospedaliero-Universitaria di FerraraFerraraItaly
  18. 18.Neuroradiology Unit, Department of Neuroscience and RehabilitationAzienda Ospedaliero-Universitaria di FerraraFerraraItaly
  19. 19.Clinica NeurologicaAzienda Ospedaliero-UniversitariaPisaItaly
  20. 20.Department of NeuroscienceMarche Polytechnic UniversityAnconaItaly
  21. 21.San Gerardo HospitalUniversity of Milano-BicoccaMonzaItaly
  22. 22.Stroke Unit, AOU SeneseSienaItaly
  23. 23.Department of NeurologyDemocritus University of Thrace, University Hospital of AlexandroupolisThraceGreece
  24. 24.International Clinic Research CenterSt. Anne’s University Hospital BrnoBrnoCzech Republic
  25. 25.Second Department of Neurology, “Attikon” Hospital, School of MedicineUniversity of AthensAthensGreece
  26. 26.Vascular Unit, 3rd Surgical Department, “Attikon” Hospital, School of MedicineUniversity of AthensAthensGreece
  27. 27.Stroke Unit, Iazzolino HospitalVibo ValentiaItaly
  28. 28.Stroke Unit, Ospedale di PortogruaroVeniceItaly
  29. 29.Neurology, Rivoli HospitalTurinItaly
  30. 30.Haemodynamic and Vascular Interventional Unit, Rivoli HospitalTurinItaly
  31. 31.Morgagni-Pierantoni HospitalForlìItaly
  32. 32.Poliambulanza HospitalBresciaItaly
  33. 33.Stroke Unit, NeurologyInsubria UniversityVareseItaly
  34. 34.UO Gravi Cerebrolesioni, San Giovanni Battista HospitalFolignoItaly
  35. 35.Stroke Unit, Department of NeurologySant’Andrea HospitalLa SpeziaItaly
  36. 36.Stroke Unit, Ospedale CivicoPalermoItaly
  37. 37.Neurology, Azienda Ospedaliera della Provincia di LodiLodiItaly
  38. 38.Stroke Unit-Department of NeurologySanta Corona HospitalPietra LigureItaly
  39. 39.Stroke Unit, Neuroscience DepartmentUniversity of ParmaParmaItaly
  40. 40.Department of Neurology and PsychiatrySapienza University of RomeRomeItaly

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