Safety of Endovascular Thrombectomy in Isolated Cervical Internal Carotid Artery Occlusion While on Oral Anticoagulation

Article information

J Stroke. 2026;28(2):321-325
Publication date (electronic) : 2026 May 28
doi : https://doi.org/10.5853/jos.2025.05918
Lukas Mayer-Suess,1,*orcid_icon, Christoph Riegler2,3,*, João Pedro Marto4,5, Pimrapat Gebert6,7, Tilman Reiff8, Marek Sykora9,10, Marcin Wiącek11, David Pakizer12, André Araújo13, Adrien ter Schiphorst14, João André Sousa15, Arno Reich16, Belen Flores Pina17, Cristina Hobeanu18, Marialuisa Zedde19, João Nuno Ramos20, Georgios Tsivgoulis21, Pedro Castro22, Sven Poli23,24, José Nuno Alves25, Anne Dusart26, Blanca Fuentes27, Herbert Tejada Meza28,29, Jelle Demeestere30, Susanne Wegener31,32, Lars Kellert33, Patricia Calleja34, Cristina Panea35,36, Christoph Vollmuth37, Karl Georg Haeusler38, Liliana Pereira39, Ronen Leker40, Timo Uphaus41, Andrea Zini42, Henrik Gensicke43,44, Gauthier Duloquin45, Taraneh Ebrahimi46, Alexander Salerno47, Cristina Tiu48, Thanh N. Nguyen49, Sebastian García-Madrona50, Marta Bilik51, Shadi Yaghi52, Halina Sienkiewicz-Jarosz53, Michał Karliński54, Stefan Krebs9, Eva Hurtíková55, Nathalia Ferreira15, João Sargento-Freitas15, João Pinho16, Isabel Rodriguez Caamaño17, Elke Ruth Gizewski56, Pierre Seners18,57, Rosario Pascarella58, Klearchos Psychogios59, Alexandra Gómez-Expósito23,24, Sara Gomes25, Flavio Bellante26, Jorge Rodríguez-Pardo27, Mario Bautista Lacambra29,60, Robin Lemmens30, Corinne Inauen31, Johannes Wischmann33, Fernando Ostos34, Vlad Tiu35,36, Miguel Rodrigues39, Issa Metanis40, Marianne Hahn41, Maria Maddalena Viola42, Simon Truessel43, Yannick Béjot45, Louisa Nitsch46, Davide Strambo47, Elena Oana Terecoasa48, Mohamad Abdalkader49, Alicia De Felipe50, Farhan Khan52, Caroline Arquizan14, Manuel Ribeiro13, Martin Roubec12,55, Izabella Tomaszewska-Lampart11, Julia Ferrari9, Peter Ringleb8, Christian H. Nolte2,3,6,61
1Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria
2Department of Neurology, Charité – Universitätsmedizin Berlin, Berlin, Germany
3Center for Stroke Research Berlin (CSB), Charité – Universitätsmedizin Berlin, Berlin, Germany
4Department of Neurology, Hospital de Egas Moniz, Centro Hospitalar Lisboa Ocidental, Lisbon, Portugal
5Lisbon Clinical Academic Center, NOVA Medical School, Universidade NOVA de Lisboa, Lisbon, Portugal
6Berlin Institute of Health at Charité – Universitätsmedizin Berlin, Berlin, Germany
7Charité – Universitätsmedizin Berlin, Institute of Biometry and Clinical Epidemiology, Berlin, Germany
8Department of Neurology, Heidelberg University Hospital, Heidelberg, Germany
9Department of Neurology, St. John’s Hospital, Vienna, Austria
10Medical Faculty, Sigmund Freud University Vienna, Vienna, Austria
11Department of Neurology, Institute of Medical Sciences, Medical College of Rzeszow University, Rzeszow, Poland
12Centre for Health Research, Faculty of Medicine, University of Ostrava, Ostrava, Czech Republic
13Department of Neuroradiology, Centro Hospitalar de Vila Nova de Gaia/Espinho, Gaia, Portugal
14Department of Neurology, Centre Hospitalier Universitaire Gui de Chauliac, Montpellier, France
15Department of Neurology, Centro Hospitalar Universitário de Coimbra, Coimbra, Portugal
16Department of Neurology, University Hospital RWTH Aachen, Aachen, Germany
17Department of Neurology, Germans Trias Hospital, Barcelona, Spain
18Neurology Department, Rothschild Foundation Hospital, Paris, France
19Neurology Unit, Stroke Unit, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, Reggio Emilia, Italy
20Department of Neuroradiology, Hospital de Egas Moniz, Centro Hospitalar Lisboa Ocidental, Lisbon, Portugal
21Second Department of Neurology, National & Kapodistrian University of Athens, Attikon University Hospital, School of Medicine, Athens, Greece
22Department of Neurology, Centro Hospitalar Universitário São João, Porto, Portugal
23Department of Neurology & Stroke, University of Tübingen, Tübingen, Germany
24Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany
25Department of Neurology, Hospital de Braga, Braga, Portugal
26Department of Neurology, CHU Charleroi, Hôpital Civil Marie Curie, Charleroi, Belgium
27Department of Neurology and Stroke Center, Hospital La Paz Institute for Health Research-IdiPAZ (La Paz University Hospital-Universidad Autónoma de Madrid), Madrid, Spain
28Stroke Unit, Department of Neurology and Interventional Neuroradiology Unit, Department of Radiology, Hospital Universitario Miguel Servet, Zaragoza, Spain
29Instituto de Investigación Sanitaria (IIS) Aragón, Zaragoza, Spain
30Neurology Department, Leuven University Hospital, Leuven, Belgium
31Department of Neurology, University Hospital Zurich and University of Zurich, Zurich, Switzerland
32Clinical Neuroscience Center, University Hospital Zurich and University of Zurich, Zurich, Switzerland
33Department of Neurology, Ludwig Maximilian University, University Hospital, Munich, Germany
34Department of Neurology and Stroke Centre, 12 de Octubre University Hospital, Instituto de Investigación Hospital 12 de Octubre (i+12), Madrid, Spain
35Department of Clinical Neuroscience, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
36Neurology Department, Elias University Emergency Hospital, Bucharest, Romania
37Department of Neurology, Universitätsklinikum Würzburg (UKW), Würzburg, Germany
38Department of Neurology, Universitätsklinikum Ulm, Ulm, Germany
39Department of Neurology, Hospital Garcia de Orta, Almada, Portugal
40Department of Neurology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel
41Department of Neurology and Focus Program Translational Neuroscience, Rhine Main Neuroscience Network, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
42IRCCS Istituto delle Scienze Neurologiche di Bologna, Department of Neurology and Stroke Center, Maggiore Hospital, Bologna, Italy
43Stroke Center and Department of Neurology, University Hospital Basel and University of Basel, Basel, Switzerland
44Neurology and Neurorehabilitation, University Department of Geriatric Medicine Felix Platter, University of Basel, Basel, Switzerland
45Université Bourgogne, Europe, CHU Dijon Bourgogne, Department of Neurology, Dijon Stroke Registry PEC2 EA7460, Dijon, France
46Division of Vascular Neurology, University Hospital Bonn, Bonn, Germany
47Stroke Center, Department of Neurological Sciences, Lausanne University Hospital, Lausanne, Switzerland
48Department of Neurology, University Emergency Hospital Bucharest, Bucharest, Romania
49Department of Radiology and Neurology, Boston University Chobanian and Avedisian School of Medicine, Boston, MA, USA
50Department of Neurology and Stroke Center, Hospital Ramón y Cajal, Madrid, Spain
51Oddział Neurologiczny z Pododdziałem Udarowym, SPS Szpital Zachodni im. Św Jana Pawła II, Grodzisk Mazowiecki, Poland
52Department of Neurology, Brown University, Providence, RI, USA
531st Department of Neurology, Institute of Psychiatry and Neurology, Warsaw, Poland
542nd Department of Neurology, Institute of Psychiatry and Neurology, Warsaw, Poland
55Comprehensive Stroke Center, Department of Neurology, University Hospital Ostrava, Ostrava, Czech Republic
56Department of Radiology, Medical University of Innsbruck, Innsbruck, Austria
57Institut de Psychiatrie et Neurosciences de Paris, Université Paris Cité, Paris, France
58Neuroradiology Unit, Ospedale Santa Maria della Misericordia, AULSS5 Polesana, Rovigo, Italy
59Acute Stroke Unit, Metropolitan Hospital, Athens, Greece
60Stroke Unit, Department of Neurology, Hospital Universitario Miguel Servet, Zaragoza, Spain
61Deutsches Zentrum für Herz-Kreislaufforschung DZHK, Berlin, Germany
Correspondence: Lukas Mayer-Suess Department of Neurology, Medical University of Innsbruck, Anichstraße 35, Innsbruck A-6020, Austria Tel: +43-512-504-83127 E-mail: Lukas.Mayer@i-med.ac.at
*These authors contributed equally as first author.
Received 2025 November 19; Revised 2026 January 21; Accepted 2026 March 26.

Dear Sir:

Recently, the large international observational Endovascular Treatment for Isolated Cervical Internal Carotid Artery Occlusion (ETIICA) study investigated the safety and efficacy of acute endovascular therapy (EVT) in patients with acute ischemic stroke and isolated cervical internal carotid artery occlusion (c-ICA-O) [1]. Three-month functional outcomes after EVT were similar to those in patients receiving best medical treatment (BMT) alone [1]. As other registries report similar findings, a randomized controlled trial seems warranted [2]. However, safety concerns in a subset of patients remain, as an increased risk of symptomatic intracranial hemorrhage (ICH) was observed in the EVT group of ETIICA compared with those receiving BMT alone (8 [1.6%] vs. 0 [0.0%]) [1]. This raises the question of the potential risk of EVT in patients with an increased risk of ICH, such as those taking oral anticoagulation (OAC) at the time of stroke.

Studies in patients undergoing EVT due to intracranial largevessel occlusion stroke have reported that prior OAC intake does not place patients at a higher risk of ICH, especially if taking a direct oral anticoagulant (DOAC) [3,4]. However, whether this holds true for patients with isolated c-ICA-O remains unknown [5].

Therefore, we aimed to evaluate the effect of OAC intake before the index stroke on the safety and efficacy of EVT in patients with isolated c-ICA-O.

Details of the ETIICA study have been published [1]. In short, the registry included patients with ischemic stroke and isolated c-ICA-Os presenting within 24 hours from the last-seen-well. This study compared BMT alone with BMT plus EVT. ETIICA included patients treated between 2018 and 2022 at 42 sites in Europe and North America. This subgroup analysis compared patients with ETIICA who underwent EVT and were on pre-stroke OAC (vitamin K antagonists or DOACs) with those who underwent EVT and were not on OAC. Patients who received bridging intravenous thrombolysis (IVT) were excluded because IVT is a confounder of ICH. Outcomes of interest were symptomatic ICH (defined as parenchymal hematoma type 2 [PH2] with an increase of at least four points on the National Institutes of Health Stroke Scale [NIHSS] score) or any hemorrhage at 24–36 hours postintervention, as well as ordinal 3-month modified Rankin Scale (mRS) scores (shift) [6].

Continuous variables are presented as mean with standard deviation and median with interquartile range, depending on the data distribution. Categorical variables are presented as absolute numbers and percentages. The baseline characteristics of patients with and without prior OAC use were compared using the chi-square test for categorical variables and either the independent t-test or the Mann-Whitney U test for continuous variables, as appropriate.

Shift analysis was performed for the 3-month mRS scores. Binary logistic regression analysis was performed for both ICH and symptomatic ICH. To adjust for potential confounding factors, we applied normalized Inverse Probability of Treatment Weighting based on a propensity score estimated using logistic regression. The model included the following predefined covariates: age, sex, pre-mRS score, NIHSS score at admission, atrial fibrillation, heart failure, arterial hypertension, current or recent smoking, previous stroke or transient ischemic attack, atherosclerosis, cardioembolism, dissection, antiplatelet use, and carotid artery stenting. Age and NIHSS score were modelled as restricted cubic splines with three knots. Statistical testing was done within an exploratory framework at a two-sided significance level of α=0.05. Statistical analyses were performed using Stata MP/18 (StataCorp. 2023, College Station, TX, USA).

A total of 285 of the 998 (28.6%) patients with ETIICA were eligible for this analysis (exclusions: 511 patients did not undergo EVT and 202 patients underwent bridging thrombolysis), of whom 64 patients had prior OAC. Table 1 presents the patient characteristics, including risk factors, stroke etiology, and clinical status at admission and during treatment.

Patient and treatment characteristics of c-ICA-O patients with and without prior OACs

Notably, even though there was a numerical difference in PH2 between patients with and without prior OAC (2 [3.2%] vs. 2 [0.9%]), no difference in occurrence risk of any ICH (9/63 [14.3%] vs. 29/220 [13.2%]; adjusted odds ratio, aOR, 1.31 [95% confidence interval, CI, 0.39–4.44]) or symptomatic ICH (2/63 [3.2%] vs. 3/220 [1.4%]; aOR, 1.26 [95% CI, 0.19–8.51]) (Figure 1 for details) was observed. This was also true in the crude, unadjusted analysis (data not shown). Furthermore, the mRS-defined functional outcome at 3 months was similar between patients with and without OAC use before EVT (aOR, 1.00 [95% CI, 0.35– 2.90]).

Figure 1.

Outcomes of EVT for acute isolated c-ICA-O with regard to prior OAC intake. (A) Effect of prior OAC on clinical (mRS) and safety outcomes after EVT for acute isolated c-ICA-O. (B) Occurrence of hemorrhage types in EVT treated participants with acute isolated c-ICA-O with regard to prior OAC intake. mRS, modified Rankin Scale; OAC, oral anticoagulation; OR, odds ratio; CI, confidence interval; PH, parenchymal hematoma; EVT, endovascular therapy; c-ICA-O, cervical internal carotid artery occlusion.

To date, the optimal care for isolated c-ICA-O remains unknown, with the safety and efficacy of acute revascularization measures being in question [2,7-9]. The ETIICA registry, the largest international registry collecting observational data of this patient population, has enabled a detailed assessment of individual treatment aspects [1]. Our subgroup analysis adds data to the safety of EVT in patients with acute stroke and isolated c-ICA-O [1]. Although ETIICA found higher rates of ICH in patients undergoing EVT compared with BMT alone, this increased risk of ICH did not stem from prior OAC use.

Our results support the notion that prior OAC use does not increase the risk of adverse bleeding outcomes in stroke patients with c-ICA-O undergoing EVT (Figure 1). This is reassuring, as approximately 1 in 7 patients with isolated c-ICA-O presented with OAC, indicating that c-ICA-O is not exclusively caused by atherosclerosis or dissection but by comorbidities requiring OAC [1]. As the call for randomized controlled clinical trials in this patient population continues, observational data defining patient characteristics that may or may not be recruited safely into such trials in the future are crucial. Although acknowledging the retrospective data collection, selection bias, lack of central reading, unblinded outcome assessment, and the missing data on OAC type (i.e., vitamin K antagonists, DOACs) and compliance, we contend that prior OAC should not be an exclusion criterion when designing a future treatment trial.

Notes

Funding statement

None

Conflicts of interest

The authors have no financial conflicts of interest.

Author contribution

Conceptualization: Lukas Mayer-Suess, Christoph Riegler, Pimrapat Gebert, João Pedro Marto, Christian H. Nolte. Methodology: Lukas Mayer-Suess, Christoph Riegler, Pimrapat Gebert, João Pedro Marto, Christian H. Nolte. Investigation: Lukas Mayer-Suess, Christoph Riegler. Statistical analysis: Pimrapat Gebert. Writing—original draft: Lukas Mayer-Suess, Christoph Riegler. Writing—review & editing: all authors. Approval of final manuscript: all authors.

References

1. Marto JP, Riegler C, Gebert P, Reiff T, Sykora M, Wiącek M, et al. Endovascular treatment for isolated cervical internal carotid artery occlusion: ETIICA study. Eur Stroke J 2025;10:694–704.
2. Meyer L, Broocks G, Alexandrou M, Lüttich Á, Larrea JÁ, Schwindt W, et al. Endovascular versus best medical treatment for Acute Carotid Occlusion BelOw Circle of Willis (ACOBOW): the ACOBOW study. Radiology 2025;314:e240293.
3. Goldhoorn RB, van de Graaf RA, van Rees JM, Lingsma HF, Dippel DWJ, Hinsenveld WH, et al. Endovascular treatment for acute ischemic stroke in patients on oral anticoagulants: results from the MR CLEAN registry. Stroke 2020;51:1781–1789.
4. Meinel TR, Kniepert JU, Seiffge DJ, Gralla J, Jung S, Auer E, et al. Endovascular stroke treatment and risk of intracranial hemorrhage in anticoagulated patients. Stroke 2020;51:892–898.
5. Meinel TR, Branca M, De Marchis GM, Nedeltchev K, Kahles T, Bonati L, et al. Prior anticoagulation in patients with ischemic stroke and atrial fibrillation. Ann Neurol 2021;89:42–53.
6. Mazya M, Egido JA, Ford GA, Lees KR, Mikulik R, Toni D, et al. 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 2012;43:1524–1531.
7. Romoli M, Mosconi MG, Pierini P, Alberti A, Venti M, Caso V, et al. Reperfusion strategies in stroke due to isolated cervical internal carotid artery occlusion: systematic review and treatment comparison. Neurol Sci 2021;42:2301–2308.
8. Mayer L, Grams A, Freyschlag CF, Gummerer M, Knoflach M. Management and prognosis of acute extracranial internal carotid artery occlusion. Ann Transl Med 2020;8:1268.
9. Kargiotis O, Psychogios K, Safouris A, Spiliopoulos S, Karapanayiotides T, Bakola E, et al. Diagnosis and treatment of acute isolated proximal internal carotid artery occlusions: a narrative review. Ther Adv Neurol Disord 2022;15:17562864221136335.

Article information Continued

Figure 1.

Outcomes of EVT for acute isolated c-ICA-O with regard to prior OAC intake. (A) Effect of prior OAC on clinical (mRS) and safety outcomes after EVT for acute isolated c-ICA-O. (B) Occurrence of hemorrhage types in EVT treated participants with acute isolated c-ICA-O with regard to prior OAC intake. mRS, modified Rankin Scale; OAC, oral anticoagulation; OR, odds ratio; CI, confidence interval; PH, parenchymal hematoma; EVT, endovascular therapy; c-ICA-O, cervical internal carotid artery occlusion.

Table 1.

Patient and treatment characteristics of c-ICA-O patients with and without prior OACs

Total (n=285) Prior OAC (n=64) No prior OAC (n=221) P
Patient characteristics
 Age (yr) 71.8±13.5 79.6±9.6 69.6±13.6 <0.01
 Sex <0.01
  Female 108 (37.9) 35 (54.7) 73 (33.0)
  Male 177 (62.1) 29 (45.3) 148 (67.0)
 Pre-stroke mRS <0.01
  mRS 0–2 241 (84.6) 46 (71.9) 195 (88.2)
  mRS 3–5 44 (15.4) 18 (28.1) 26 (11.8)
 Pre-existent conditions*
  Atrial fibrillation 105 (36.8) 58 (90.6) 47 (21.3) <0.01
  Heart failure 80 (28.1) 27 (42.2) 53 (24.0) <0.01
  Arterial hypertension 212 (74.4) 55 (85.9) 157 (71.0) 0.02
  Diabetes mellitus 86 (30.2) 18 (28.1) 68 (30.8) 0.68
  Dyslipidemia 142 (49.8) 32 (50.0) 110 (49.8) 0.97
  Coronary artery disease 64 (22.5) 16 (25.0) 48 (21.7) 0.58
  Current smoking 75 (26.3) 4 (6.2) 71 (32.1) <0.01
  Prior stroke 67 (23.5) 20 (31.2) 47 (21.3) 0.10
Stroke aetiology†
 Atherosclerosis 166 (58.2) 28 (43.8) 138 (62.4) <0.01
 Cardioembolism 91 (31.9) 43 (67.2) 48 (21.7) <0.01
 Dissection 28 (9.8) 1 (1.6) 27 (12.2) 0.01
 Other determined cause 1 (0.4) 0 (0.0) 1 (0.5) 0.59
 Undetermined 12 (4.2) 1 (1.6) 11 (5.0) 0.23
Medication at admission
 Antiplatelets 89 (31.2) 2 (3.1) 87 (39.4) <0.01
 Statins 109 (38.2) 28 (43.8) 81 (36.7) 0.25
Clinical presentation
 NIHSS admission 13 (7–18) 14 (8–19) 12 (6–18) 0.05
 CT ASPECTS [0–10] 10 (9–10) 10 (9–10) 10 (9–10) 0.43
 MRI ASPECTS [0–10] 8 (7–9) 8 (8–8) 8 (6–9) 0.98
 Combined ASPECTS 10 (9–10) 10 (9–10) 10 (9–10) 0.38
 Penumbra/core mismatch (>1.2) 99 (79.8) 25 (83.3) 74 (78.7) 0.58
Treatment
 Stenting 132 (46.3) 20 (31.2) 112 (50.7) <0.01
 Time course (min)
  Last seen well-to-door 233 (90–565) 183 (80–476) 275 (92–643) 0.12
  Door-to-puncture 112 (59–220) 94 (54–182) 113 (60–233) 0.36
  Door-to-recanalization 198 (120–302) 188 (108–253) 201 (130–323) 0.14
 General anesthesia 96 (33.7) 22 (34.4) 74 (33.5) 0.89

Values given as mean±standard deviation, n (%), or median (25th–75th percentiles). P-values for group differences are given (significance level of α=0.05).

c-ICA-O, cervical internal carotid artery occlusion; OAC, oral anticoagulation; mRS, modified Rankin Scale; NIHSS, National Institutes of Health Stroke Scale; CT, computed tomography; ASPECTS, Alberta Stroke Program Early CT Score; MRI, magnetic resonance imaging.

*

One patient can have more than one pre-existent condition;

†

In competing aetiologies (total of 13 patients), both were assigned.