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Safety and Outcome of Carotid Dissection Stenting During the Treatment of Tandem Occlusions

A Pooled Analysis of TITAN and ETIS
and on behalf of TITAN and ETIS Investigators*
Originally publishedhttps://doi.org/10.1161/STROKEAHA.120.030038Stroke. 2020;51:3713–3718

Abstract

Background and Purpose:

The efficacy of endovascular therapy in patients with acute ischemic stroke due to tandem occlusion is comparable to that for isolated intracranial occlusion in the anterior circulation. However, the optimal management of acute cervical internal carotid artery lesions is unknown, especially in the setting of carotid dissection, but emergency carotid artery stenting (CAS) is frequently considered. We investigated the safety and efficacy of emergency CAS for carotid dissection in patients with acute stroke with tandem occlusion in current clinical practice.

Methods:

We retrospectively analyzed a prospectively maintained database composed of 2 merged multicenter international observational real-world registries (Endovascular Treatment in Ischemic Stroke and Thrombectomy in Tandem Lesion). Data from endovascular therapy performed in the treatment of tandem occlusions related to acute cervical carotid dissection between January 2012 and January 2019 at 24 comprehensive stroke centers were analyzed.

Results:

The study assessed 136 patients with tandem occlusion due to dissection, including 65 (47.8%) treated with emergency CAS and 71 (52.2%) without. The overall rates of favorable outcome (90-day modified Rankin Scale score, 0–2) and successful reperfusion (modified Thrombolysis in Cerebral Infarction, 2b–3) were 58.0% (n=76 [95% CI, 49.6%–66.5%]) and 77.9% (n=106 [95% CI, 71.0%–85.0%]), respectively. In subgroup analyses, the rate of successful reperfusion (89.2% versus 67.6%; adjusted odds ratio, 2.24 [95% CI, 1.33–3.77]) was higher after CAS, whereas the 90-day favorable outcome (54.3% versus 61.4%; adjusted odds ratio, 0.84 [95% CI, 0.58–1.22]), symptomatic intracerebral hemorrhage (sICH; 10.8% versus 5.6%; adjusted odds ratio, 1.59 [95% CI, 0.79–3.17]), and 90-day mortality (8.0% versus 5.8%; adjusted odds ratio, 1.00 [95% CI, 0.48–2.09]) did not differ. In sensitivity analyses of patients with successful intracranial reperfusion, CAS was not associated with an improved clinical outcome.

Conclusions:

Emergency stenting of the dissected cervical carotid artery during endovascular therapy for tandem occlusions seems safe, whatever the quality of the intracranial reperfusion.

The best endovascular therapy (EVT) for anterior circulation tandem occlusion strokes is unclear.1,2 Tandem occlusions are mostly related to carotid dissection or atherosclerosis, with specific patient profiles, recurrence rates, and prognoses. The mechanism of tandem occlusion may influence EVT. Systematic carotid artery stenting (CAS) in the treatment of carotid dissection responsible for tandem occlusion is controversial. Despite extensive data on the clinical benefits of CAS in the setting of atheromatous tandem occlusions,3–6 the treatment and outcome may differ in younger patients with lower rates of recurrent ischemic events. Therefore, this study investigated whether emergency CAS for carotid dissection in the context of tandem occlusion was safe and associated with better clinical outcomes.

Methods

Population

This was a retrospective analysis of prospectively maintained multicenter observational databases. The study population comprised 2 merged databases: Endovascular Treatment in Ischemic Stroke (URL: https://www.clinicaltrials.gov; Unique identifier: NCT03776877) from May 2012 to January 2019 and Thrombectomy in Tandem Lesion from January 2012 to September 2016. Endovascular Treatment in Ischemic Stroke is an ongoing French prospective registry that collects data from consecutive patients undergoing EVT for large-vessel occlusion at 6 high-volume stroke centers.7 The Thrombectomy in Tandem Lesion collaboration pooled individual data on nonrandomized thrombectomy databases from 18 international centers for all consecutive anterior circulation tandem occlusions treated with EVT.3 Our analysis included patients with anterior circulation tandem occlusion due to dissection treated by EVT. Data collection and analyses were approved by local institutional review boards. Oral informed consent was obtained from patients or their relatives. The study data are available from the corresponding author upon reasonable request.

Endovascular Procedure

The indications for EVT were based on the timeframe, imaging data, global comorbidities of the patients, and standard guidelines after a multidisciplinary discussion. The EVT performed depended on the patient’s condition and local protocol. The EVT strategy was left to the discretion of the interventionist. Intravenous thrombolysis was performed within 4.5 hours after onset if eligible. Figure 1 shows a case of carotid dissection stenting during EVT for tandem occlusion.

Figure 1.

Figure 1. A 52-y-old patient presenting with right hemiplegia and aphasia with tandem occlusion related to dissection. Magnetic resonance imaging performed 4 hours after onset demonstrated slight infarction of lenticular nuclei and insula (ASPECT 8) and left tandem occlusion. Intravenous thrombolysis was performed at the primary center. Complete intracranial reperfusion (A and B) was achieved first and confirmed the dissection of the subpetrosal cervical internal carotid artery (C). Considering the persistent high-grade stenosis, carotid artery stenting was performed at the end of the procedure and intravenous 250 mg Aspirin was administered (D). Day-1 imaging revealed no extension of infarction, asymptomatic petechial infarction, and patency of the stent. A dual antiplatelet therapy was initiated.

Data Collection

For details on data collection, see the Data Supplement.

Statistical Analysis

For details on statistical analysis, see the Data Supplement.

Results

The study enrolled 136 patients with tandem occlusion stroke with dissection: 65 (47.8%) were treated with CAS and 71 (52.2%) without. Table I in the Data Supplement summarizes the patients and treatments and Table II in the Data Supplement the characteristics according to CAS status. Their mean age was 51.9 (SD, 11.7) years, 67.6% (n=92) were men, and the median admission National Institutes of Health Stroke Scale score was 15 (interquartile range, 12–19). The median time from onset to puncture was 270 min (interquartile range, 170–290). At 90 days, 58.0% (n=76 [95% CI, 49.6%–66.5%]) had favorable outcomes (modified Rankin Scale score, 0–2) and 6.7% had died (n=9 [95% CI, 3.2%–12.6%]). Successful reperfusion (modified Thrombolysis in Cerebral Infarction, 2b–3) occurred in 77.9% (n=106 [95% CI, 71.0%–85%]) and 55 (63.2%) had 24-hour permeability of the cervical internal carotid artery (95% CI, 52.2%–73.3%). Procedural complications occurred in 11.8% (n=16 [95% CI, 6.3%–17.2%]) and symptomatic intracerebral hemorrhage in 8.2% (n=11 [95% CI, 4.2%–14.2%]).

As shown in Table II in the Data Supplement, the baseline characteristics of patients with and without CAS were comparable. The rate of favorable outcome did not differ significantly between the groups (Table; 54.3%–61.4%), with an adjusted odds ratio (aOR) for CAS of 0.84 (95% CI, 0.58–1.22). Similarly, there was no difference in the overall modified Rankin Scale distribution (Figure 2; aOR, 0.97 [95% CI, 0.51–1.84]). CAS was associated with greater rates of successful reperfusion (aOR, 2.24 [95% CI, 1.33–2.77]) and internal carotid artery patency (aOR, 1.82 [95% CI, 1.14–2.90]). There were no between-group differences in mortality (aOR, 1.00 [95% CI, 0.48–2.09]), procedural complications (aOR, 0.74 [95% CI, 0.42–1.31]), or symptomatic intracerebral hemorrhage (aOR, 1.59 [95% CI, 0.79–3.17]). In sensitivity analyses restricted to patients with successful reperfusion, CAS remained unassociated with improved outcomes (aOR, 0.70 [95% CI, 0.45–1.08] for favorable outcome and aOR, 0.83 [95% CI, 0.40–1.71] for overall 90-day modified Rankin Scale distribution).

Table. Comparison in Outcomes Between Patients With and Without CAS

CharacteristicsExtracranial CASUnadjusted*Adjusted
No (n=71)Yes (n=65)OR (95% CI)P valueOR (95% CI)P value
Angiographic outcomes
 mTICI 2b/348 (67.6)58 (89.2)3.97 (1.57 to 10.05)0.0042.24 (1.33 to 3.77)0.002
 mTICI 317 (23.9)22 (33.9)1.63 (0.77 to 3.45)0.202.20 (1.70 to 3.22)0.25
 Procedural complications10 (14.1)6 (9.2)0.62 (0.21 to 1.81)0.380.74 (0.42 to 1.31)0.30
 Patency of extracranial carotid artery37 (52.0)52 (80.2)3.79 (1.52 to 9.45)0.0051.82 (1.14 to 2.91)0.013
Clinical outcomes
 90-day favorable outcome44 (61.4)35 (54.3)0.75 (0.37 to 1.49)0.410.84 (00.58 to 1.22)0.36
 90-day mortality4 (5.8)5 (8.0)1.42 (0.36 to 5.56)0.621.00 (0.48 to 2.09)0.99
 24 h change in NIHSS, mean (95% CI)§−2.3 (−4.1 to −0.5)−2.7 (−4.9 to −0.5)−0.40 (−3.25 to 2.46)0.78−0.68 (−3.61 to 2.24)0.65
Hemorrhagic complications
 sICH4 (5.6)7 (10.8)2.02 (0.56 to 7.25)0.281.59 (0.79 to 3.17)0.19

CAS indicates carotid artery stenting; mTICI, modified Thrombolysis in Cerebral Infarction; NIHSS, National Institutes of Health Stroke Scale; OR, odds ratio; sICH, symptomatic intracranial hemorrhage.

* Calculated using stenting group as reference.

† Calculated using stenting group as reference after adjustment for hypertension, hypercholesterolemia, site of occlusion, and general anesthesia.

‡ Favorable outcome is defined as an mRS score of 0–2.

§ Mean change (95% CI) adjusted for admission NIHSS score.

∥ Mean between group difference in change (95% CI) adjusted for admission NIHSS score.

¶ Mean between group difference in change (95% CI) adjusted for admission NIHSS score and hypertension, hypercholesterolemia, site of occlusion, and general anesthesia.

Figure 2.

Figure 2. Ninety-day clinical outcome according to use or not of carotid artery stenting in the overall study population and inpatients with successful reperfusion (modified Thrombolysis in Cerebral Infarction [mTICI], 2b/3).A, Overall population; (B) patients with intracranial successful reperfusion (mTICI 2b/3). Common odds ratio (cOR) calculated for 1-point improvement in modified Rankin Scale (mRS; 5 and 6 pooled together) by using an ordinal logistic regression model. mRS score: 0 indicates no symptoms; 1, no clinically relevant disability; 2, slight disability (able to look after own affairs without assistance but not to full extent); 3, moderate disability (requires some help but able to walk unassisted); 4, moderately severe disability (requires assistance and unable to walk unassisted); 5, severe disability (requires constant nursing care); and 6, dead.

Discussion

Emergency CAS for dissection with tandem occlusion strokes treated with intracranial thrombectomy was safe and had higher rates of successful reperfusion and carotid artery patency at day 1. However, CAS was not associated with an improved clinical outcome at 90 days.

There are 2 steps in EVT for tandem occlusions: intracranial recanalization and cervical lesion management. Intracranial treatment is frequently performed first to hasten early brain reperfusion. If intracranial reperfusion fails, clinicians would obviously be reluctant to perform CAS considering the drawbacks (eg, a potentially risky endovascular maneuver with limited expected benefit, probability of extended infarction, and required antiplatelet therapy). To eliminate the significant difference in favorable recanalization between the groups with and without CAS, we performed a sensitivity analysis considering only patients with successful intracranial reperfusion and CAS remained unassociated with a better outcome. Consequently, we found that even for patients with a final modified Thrombolysis in Cerebral Infarction of 2b–3, adding CAS to intracranial thrombectomy was not associated with a better clinical outcome. To study the influence of CAS, the final modified Thrombolysis in Cerebral Infarction score in such a mechanical thrombectomy-specific population should not be considered as an outcome, but as a confounding factor. The decision to perform CAS is intrinsically linked to the intracranial success. However, patients treated with CAS had high rates of successful reperfusion and day 1 carotid patency, which was reported to be a strong predictor of a favorable outcome.8,9

Several publications have mentioned positive effects of emergency CAS in patients with tandem occlusion strokes.3–6 However, most included patients had atherosclerotic lesions, and the current literature provides arguments for the superiority of CAS versus conservative management. Atherosclerosis seems to be associated with a high risk of recurrent stroke without CAS. A preferential location on the bulbar internal carotid artery also makes it easily accessible for CAS (versus carotid dissection, which is usually located at the subpetrosal internal carotid artery). Dissection and atherosclerosis are different pathologies. Few studies consider only dissection.5 Conservative management of cervical lesions in such tandem occlusion subtypes has been reported to be safe and efficient.10 Several arguments favor this management: re-embolism from dissection and recurrent ischemic strokes are extremely rare.11 The circle of Willis is often functional. CAS can be technically difficult due to cervical loops, challenging catheterization of the true lumen, and the peri-operative risk of an intracranial embolus. Antiplatelet therapy associated with CAS and its interaction with intravenous thrombolysis may be limited by the potential risk of intracerebral hemorrhage, although recent data reported its safety in atherosclerotic tandem occlusions.12 The delayed carotid occlusion rate after emergency CAS is not negligible, and its clinical impact is controversial.9,13

Our study is the first to explore the safety and efficacy of emergency dissection CAS in a large population. We found no evidence that CAS improved that outcome, although it appeared to be safe. Given its safety, CAS might be considered in the management of tandem occlusion related to dissection, especially in the setting of high-grade residual stenosis after intracranial recanalization, insufficient circle of Willis patency, or a cervical endoluminal threatening thrombus. The ongoing Thrombectomy in Tandem Lesion randomized trial will evaluate the effect of emergency CAS in anterior tandem strokes, due to either atherosclerosis or dissection.14

Our study has several limitations, mainly due to its retrospective nature. The endovascular strategies, stenting protocols, and antiplatelet regimens were not standardized. Due to the rarity of tandem occlusion related to dissection and difficulty forming large subgroups, the statistical analysis may lack power.

Conclusions

Emergency CAS of dissection in the setting of tandem occlusions treated with EVT is safe, but was not associated with an improved clinical outcome. CAS could be considered in the context of persistent high-risk, high-grade stenosis dissection of the carotid artery after intracranial reperfusion.

Nonstandard Abbreviations and Acronyms

aOR

adjusted odds ratio

CAS

carotid artery stenting

EVT

endovascular treatment

IVT

intravenous thrombolysis

Acknowledgments

Ethics approval was obtained from the local institutional review board.

Supplemental Materials

Expanded Material and Methods

Tables I and II

Appendix

ETIS Investigators

Hocine Redjem, Simon Escalard, Jean-Philippe Desilles, Hocine Redjem, Gabriele Ciccio; Stanislas Smajda, Robert Fahed, Mikael Obadia, Candice Sabben, Ovide Corabianu, Thomas de Broucker, Didier Smadja, Sonia Alamowitch, Olivier Ille, Eric Manchon, Pierre-Yves Garcia, Guillaume Taylor, Malek Ben Maacha, Frédéric Bourdain, Jean-pierre Decroix, Adrien Wang, Serge Evrard, Maya Tchikviladze, Oguzhan Coskun, Federico Di Maria, Georges Rodesh, Morgan Leguen, Marie Tisserand, Fernando Pico, Haja Rakotoharinandrasana, Philippe Tassan, Roxanna Poll, Norbert Nighoghossian, Roberto Riva, Omer Eker, Francis turjman, Laurent Derex, Tae-Hee Cho, Laura Mechtouff, Anne Claire Lukaszewicz, Frédéric Philippeau, Serkan Cakmak, Karine Blanc-Lasserre, Anne-Evelyne Vallet, Xavier Barreau, Jérôme Berge, Patrice Menegon, Ludovic Lucas, Stéphane Olindo, Pauline Renou, Sharmila Sagnier, Mathilde Poli, Sabrina Debruxelles, François Rouanet, Thomas Tourdias, Jean-Sebastien Liegey, Lili Detraz, Benjamin Daumas-Duport, Pierre-Louis Alexandre, Monica Roy, Cédric Lenoble, Vincent L’allinec, Jean-Baptiste Girot, Hubert Desal, Serge Bracard, René Anxionnat, Marc Braun, Anne-Laure Derelle, Romain Tonnelet, Liang Liao, François Zhu, Emmanuelle Schmitt, Sophie Planel, Lisa Humbertjean, Gioia Mione, Jean-Christophe Lacour, Mathieu Bonnerot, Nolwenn Riou-Comte, Vincent Costalat, Grégory Gascou, Pierre-Henri Lefèvre, Imad Derraz, Carlos Riquelme, Caroline Arquizan, Nicolas Gaillard, Isabelle Mourand, Lucas Corti, Federico Cagnazzo

Thrombectomy in Tandem Lesion Investigators

Mohammad Anadani, Alejandro Spiotta, Ali Alawieh, Francis Turjman, Diogo Haussen, Raul Nogueira, Panagiotis Papanagiotou, Adnan H. Siddiqui, Franziska Dorn, Christophe Cognard, Marc Ribo, Marios Psychogios, Marc Antoine Labeyrie, Alessandra Biondi, Jonathan Andrew Grossberg, Adrien Guenego, Julien Darcourt, Isabelle Vukasinovic, Elisa Pomero, Jason Davies, Leonardo Renieri, Corentin Hecker, Maria Muchada Muchada, Emmanuel Houdart, Raymond Turner, Aquilla Turk, Imran Chaudry, Johanna Lockau, Andreas Kastrup, Daniel Behme, Hussain Shallwani, Maurer Christopher, Gioia Mione

Footnotes

*A list of all TITAN and ETIS Investigators is given in the Appendix.

For Sources of Funding and Disclosures, see page 3717.

The Data Supplement is available with this article at https://www.ahajournals.org/doi/suppl/10.1161/STROKEAHA.120.030038.

Correspondence to: Gaultier Marnat, MD, Department of Neuroradiology, Hôpital Pellegrin, Pl Amélie Raba-Léon, 33000 Bordeaux, France. Email

References

  • 1. Jacquin G, Poppe AY, Labrie M, Daneault N, Deschaintre Y, Gioia LC, Odier C, Raymond J, Roy D, Weill A, et al. Lack of consensus among stroke experts on the optimal management of patients with acute tandem occlusion.Stroke. 2019; 50:1254–1256. doi: 10.1161/STROKEAHA.118.023758LinkGoogle Scholar
  • 2. Assis Z, Menon BK, Goyal M, Demchuk AM, Shankar J, Rempel JL, Roy D, Poppe AY, Yang V, Lum C, et al; ESCAPE Trialists. Acute ischemic stroke with tandem lesions: technical endovascular management and clinical outcomes from the ESCAPE trial.J Neurointerv Surg. 2018; 10:429–433. doi: 10.1136/neurintsurg-2017-013316CrossrefMedlineGoogle Scholar
  • 3. Papanagiotou P, Haussen DC, Turjman F, Labreuche J, Piotin M, Kastrup A, Steglich-Arnholm H, Holtmannspötter M, Taschner C, Eiden S, et al; TITAN Investigators. Carotid stenting with antithrombotic agents and intracranial thrombectomy leads to the highest recanalization rate in patients with acute stroke with tandem lesions.JACC Cardiovasc Interv. 2018; 11:1290–1299. doi: 10.1016/j.jcin.2018.05.036CrossrefMedlineGoogle Scholar
  • 4. Jadhav AP, Zaidat OO, Liebeskind DS, Yavagal DR, Haussen DC, Hellinger FR, Jahan R, Jumaa MA, Szeder V, Nogueira RG, et al. Emergent management of tandem lesions in acute ischemic stroke.Stroke. 2019; 50:428–433. doi: 10.1161/STROKEAHA.118.021893LinkGoogle Scholar
  • 5. Compagne KCJ, Goldhoorn RB, Uyttenboogaart M, van Oostenbrugge RJ, van Zwam WH, van Doormaal PJ, Dippel DWJ, van der Lugt A, Emmer BJ, van Es ACGM; MR CLEAN Investigators. Acute endovascular treatment of patients with ischemic stroke from intracranial large vessel occlusion and extracranial carotid dissection.Front Neurol. 2019; 10:102. doi: 10.3389/fneur.2019.00102CrossrefGoogle Scholar
  • 6. Sadeh-Gonik U, Tau N, Friehmann T, Bracard S, Anxionnat R, Derelle AL, Tonnelet R, Liao L, Richard S, Armoiry X, et al. Thrombectomy outcomes for acute stroke patients with anterior circulation tandem lesions: a clinical registry and an update of a systematic review with meta-analysis.Eur J Neurol. 2018; 25:693–700. doi: 10.1111/ene.13577CrossrefMedlineGoogle Scholar
  • 7. Boisseau W, Fahed R, Lapergue B, Desilles JP, Zuber K, Khoury N, Garcia J, Maïer B, Redjem H, Ciccio G, et al; ETIS Investigators. Predictors of parenchymal hematoma after mechanical thrombectomy: a multicenter study.Stroke. 2019; 50:2364–2370. doi: 10.1161/STROKEAHA.118.024512LinkGoogle Scholar
  • 8. Bricout N, Personnic T, Ferrigno M, Labreuche J, Estrade L, Bretzner M, Leclerc X, Cordonnier C, Boulouis G, Henon H. Day 1 extracranial internal carotid artery patency is associated with good outcome after mechanical thrombectomy for tandem occlusion.Stroke. 2018; 49:2520–2522. doi: 10.1161/STROKEAHA.118.022495LinkGoogle Scholar
  • 9. Traenka C, Grond-Ginsbach C, Goeggel Simonetti B, Metso TM, Debette S, Pezzini A, Kloss M, Majersik JJ, Southerland AM, Leys D, et al; CADISP-Plus Study Group. Artery occlusion independently predicts unfavorable outcome in cervical artery dissection.Neurology. 2020; 94:e170–e180. doi: 10.1212/WNL.0000000000008654CrossrefGoogle Scholar
  • 10. Marnat G, Bühlmann M, Eker O, Gralla J, Machi P, Fischer U, Riquelme C, Arnold X, Bonafé A, Jung S, et al. Multicentric experience in distal-to-proximal revascularization artery dissection.AJNR Am J Neuroradiol. 2018; 39:1093–1099. doi: 10.3174/ajnr.A5640CrossrefMedlineGoogle Scholar
  • 11. Markus HS, Levi C, King A, Madigan J, Norris J; Cervical Artery Dissection in Stroke Study (CADISS) Investigators. Antiplatelet therapy vs anticoagulation therapy in cervical artery dissection: the cervical artery dissection in stroke study (CADISS) randomized clinical trial final results.JAMA Neurol. 2019; 76:657–664. doi: 10.1001/jamaneurol.2019.0072CrossrefGoogle Scholar
  • 12. Zhu F, Anadani M, Labreuche J, Spiotta A, Turjman F, Piotin M, Steglich-Arnholm H, Holtmannspötter M, Taschner C, Eiden S, et al; TITAN Investigators. Impact of antiplatelet therapy during endovascular therapy for tandem occlusions: a collaborative pooled analysis.Stroke. 2020; 51:1522–1529. doi: 10.1161/STROKEAHA.119.028231LinkGoogle Scholar
  • 13. Pop R, Zinchenko I, Quenardelle V, Mihoc D, Manisor M, Richter JS, Severac F, Simu M, Chibbaro S, Rouyer O, et al. Predictors and clinical impact of delayed stent thrombosis after thrombectomy for acute stroke with tandem lesions.AJNR Am J Neuroradiol. 2019; 40:533–539. doi: 10.3174/ajnr.A5976CrossrefMedlineGoogle Scholar
  • 14. Zhu F, Hossu G, Soudant M, Richard S, Achit H, Beguinet M, Costalat V, Arquizan C, Consoli A, Lapergue B, et al. Effect of emergent carotid stenting during endovascular therapy for acute anterior circulation stroke patients with tandem occlusion: a multicenter, randomized, clinical trial (TITAN) protocol [published online June 9, 2020].Int. J. Stroke. 2020:1747493020929948. doi: 10.1177/1747493020929948CrossrefGoogle Scholar

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