Dissection Dilemma: Risk Stratification and Antithrombotic Selection

HomeStroke: Vascular and Interventional NeurologyVol. 3, No. 3Dissection Dilemma: Risk Stratification and Antithrombotic Selection Open AccessEditorialPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citations ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toOpen AccessEditorialPDF/EPUBDissection Dilemma: Risk Stratification and Antithrombotic Selection Mary Penckofer and James E. Siegler Mary PenckoferMary Penckofer *Correspondence to: Mary Penckofer, Cooper Medical School of Rowan University, 401 Broadway, Camden, NJ 08103. E‐mail: E-mail Address: [email protected] , Cooper Medical School of Rowan University, , Camden, , NJ, Search for more papers by this author and James E. SieglerJames E. Siegler , Cooper University Hospital, Cooper Neurological Institute, , Camden, , NJ, Search for more papers by this author Originally published2 May 2023https://doi.org/10.1161/SVIN.123.000841Stroke: Vascular and Interventional Neurology. 2023;3:e000841Cervical artery dissection (CAD) remains an infrequent cause of ischemic stroke, accounting for ≈1% to 2% of ischemic strokes. CAD is a larger contributor of ischemic stroke in young adults aged <50 years, causing up to 25% ischemic strokes in this population.1, 2 Historically, there has been a preference for vitamin K antagonists for use in the secondary prevention of stroke in CAD; however, 2 randomized clinical trials have shown that antiplatelet therapy is not noninferior to anticoagulation.1, 2 Despite the strengths of these 2 trials, many providers continue to use anticoagulation in patients with CAD because of certain trial limitations, as well as the favorable safety profile of certain direct oral anticoagulants when compared with aspirin.3 Although it is true that data are lacking on the benefit of dual antiplatelet therapy, it is also used in the secondary prevention of CAD.Medical decision making in these scenarios is contingent on clinical judgment and extrapolation of the best available evidence when there are limitations in trial methods, small sample sizes, early trial termination, or lack of other high‐quality published data on the subject.4 Equipoise in randomizing certain patients to aspirin when there is a free‐floating thrombus or randomizing others to long‐term anticoagulation when there is a minor vessel wall irregularity is lacking. Therefore, there is considerable variability in secondary prevention preferences for CAD. In one single‐center experience across a 4‐year period (n=149 with CAD), 26% were treated with a direct oral anticoagulant, 47% were treated with warfarin or heparin, and 27% were treated with an antiplatelet(s).5 Given the nonrandomized treatment allocation in this retrospective analysis, there were important differences between groups; notably, patients treated with a direct oral anticoagulant or warfarin/heparin had more severe luminal stenosis or occlusion when compared with patients treated with antiplatelet(s) (62% versus 60% versus 23%; P<0.05). A separate prospective cohort study of 298 patients reported 68% of patients were treated with anticoagulation, whereas 32% received antiplatelet therapy.6 Irrespective of treatment allocation, it has been shown that the short‐term risk of subsequent ischemic stroke in CAD is low. These rates have ranged from 1% to 2%5, 6, 7 to up to 8%.1 These low rates of subsequent stroke limit comparative analyses between antithrombotic strategies. The CADISS (Cervical Artery Dissection in Ischemic Stroke Study) investigators estimated a randomized clinical trial would require nearly 5000 patients in each treatment arm to identify a statistically significant 1% difference in treatment effect.8To address these challenges in managing CAD, more comprehensive risk stratification is necessary to determine which patients are likely to benefit from more aggressive secondary prevention strategies. Risk factors for subsequent cerebral ischemia following acute CAD have been identified. For example, the greatest risk of subsequent ischemia following acute CAD is a symptomatic index cerebrovascular event in the first 30 days of dissection, with all ischemic events from CADISS occurring within 10 days of randomization.8 The degree of luminal stenosis or presence of an occlusion is also associated with heightened risk of ischemic infarction.7, 9 Furthermore, tobacco use and the presence of multiple simultaneous dissections have also been associated with a greater risk of recurrent ischemic events,7 but whether anticoagulation should be used in the presence of these factors (or combination antithrombotics over single antiplatelet therapy) is unclear. In addition, a factor worth considering when determining therapy is the risk of intracerebral hemorrhage, as this is a risk with any antithrombotic therapy.1 Patients known to be at greater risk of intracerebral hemorrhage include those with an older age, those with hypertension, those using anticoagulation, and those with a history of ischemic stroke.10 Individuals with these risk factors could therefore benefit from more intensive observation, management, and treatment following CAD to prevent further vascular events.With advances in neuroimaging, high‐risk dissection features can be abstracted; and more sophisticated algorithms for predicting ischemic events can be developed. At our center, we routinely image patients with computed tomography angiography to identify intraluminal and extraluminal vessel pathologic conditions (e.g., nonocclusive thrombus or soft or calcified plaque); and for many patients with CAD, we will consider conventional angiography. Alternatively, magnetic resonance imaging with angiography permits noninvasive evaluation of the cervical arterial tree and characterization of luminal stenosis and thrombus formation, both of which carry a greater risk of cerebral ischemia.7, 9 Furthermore, high‐resolution magnetic resonance imaging with angiography is increasingly useful in the detection of high‐risk atherosclerotic plaques, such as those with intraplaque hemorrhage and neovascularization.11With heightened precision in estimating risk of recurrence at the individual level, a more targeted population of patients with symptomatic CAD may be selected for enrollment in future trials. However, this must be tempered with the belief in equipoise for randomizing such patients to a single antiplatelet therapy, which may not be universally accepted. In addition, the duration of higher potency or combination antithrombotics in these circumstances is unclear. It is likely that the benefit of anticoagulation in these patients, if any benefit were to exist, is in the first few weeks after symptom onset. Currently, the 2021 American Heart Association guidelines recommend antithrombotic therapy for at least 3 months, and either warfarin or aspirin may be considered.12Although treatment has been historically centered around thrombus formation, certain mechanical factors ought to be considered in the management of CAD. Evidence is lacking in this regard; however, it is reasonable to counsel patients on the avoidance of traumatic head or neck injury. (It remains unclear which activities ought to be avoided, and for how long.12) Observational cohort data indicate that a high proportion of patients with CAD have underlying connective tissue disease, which predisposes them to dissection injury.13 In patients with additional nonatherosclerotic vasculopathic changes (eg, “stack‐of‐coins” appearance of cervical vessels), it may be advantageous to obtain abdominal vascular imaging to confirm the suspicion of a connective tissue disorder. (That said, there is no evidence to support differential treatment of CAD in patients with versus without connective tissue disorders.) Local physical factors, like styloid process length, should also be evaluated. Elongated styloid processes have been associated with cervical carotid dissection,14 and recurrence of dissection is not likely to be mitigated with any class of antithrombotics. Although data are lacking, in extreme cases, styloid resection and/or carotid stenting is implemented with the aim of preventing recurrent CAD and dissection‐associated ischemic events.15 In addition, there are a variety of environmental factors that are associated with CAD that include forceful neck movements, even those as benign as chiropractic manipulation.16 Whatever the proximate cause, the presence of intraluminal thrombus is also used to justify more aggressive antithrombotic strategies in secondary prevention, as this is strongly associated with ischemic stroke following CAD.17Altogether, the optimal strategy for prevention of recurrent ischemic strokes following CAD is best determined at the individual patient level (Figure ). Given the rarity of CAD, and the additional rarity of recurrent stroke following symptomatic CAD, it may be difficult to confirm superiority of any antithrombotic strategy against aspirin in a randomized clinical trial. Observational cohort studies, and consolidation of multicenter data, may clarify the optimal treatment duration for secondary prevention and identify the patient population(s) most likely to benefit from more aggressive, early intervention.Download figureDownload PowerPointFIGURE Case examples of cervical artery dissection with delayed recurrence, highlighting the heterogeneous mechanisms and management strategies.Top row: A 50‐year‐old previously healthy man who was renovating his home and hyperextending his neck doing ceiling work presented with sudden left‐sided clumsiness and slurred speech; he was found to have a left V1/V2 junction nonocclusive thrombus (arrow) on axial computed tomography angiography (CTA) of the neck (A), with associated posterior‐inferior cerebellar artery occlusion. The remainder of the CTA scan did not show significant atherosclerosis, and transthoracic echocardiography, electrocardiography, cardiac telemetry, lipid panel, and hemoglobin A1c results were normal. He was treated with aspirin and clopidogrel, which was simplified to aspirin after several weeks. Repeated CTA of the neck 5 months later (B) showed interval improvement in vessel irregularity, concerning for improving dissection. He returned 24 months later with recurrent left‐sided weakness, clumsiness, and slurred speech, with potential recurrence of dissection on axial CTA or nonocclusive thrombus formation (C) and with new infarcts in the right thalamus and cerebellar vermis on diffusion‐weighted magnetic resonance imaging (D). The patient resumed taking aspirin and clopidogrel. Bottom row: A 45‐year‐old previously healthy and athletic man who presented with moderate expressive aphasia in the setting of a spontaneous left cervical internal carotid artery (ICA) dissection, for which he underwent angiography (E) with thrombectomy and emergent ICA stenting. Echocardiography, electrocardiography, cardiac telemetry, lipid panel, and hemoglobin A1c results were normal. Three‐dimensional reconstruction of CTA of the neck (F), illustrating proximity of left styloid process to the region of cervical ICA dissection, consistent with Eagle syndrome, now status post stenting. He was treated with aspirin and clopidogrel for 90 days. Thirty‐six months after the initial dissection, while now on aspirin monotherapy, the patient re‐presented with a spontaneous right cervical ICA dissection with occlusion, with styloid process tips adjacent to both cervical ICAs (arrowheads), as shown on the axial CTA of the neck (G). The patient underwent emergent thrombectomy and stent placement at the time of each dissection event and is currently maintained on aspirin and clopidogrel. Asterisks indicate arterial lumen.Sources of FundingNone.DisclosureNone.AcknowledgmentsNone.Footnotes*Correspondence to: Mary Penckofer, Cooper Medical School of Rowan University, 401 Broadway, Camden, NJ 08103. E‐mail: [email protected]eduThe opinions expressed in this article are not necessarily those of the editors, the American Heart Association, or the Society of Vascular and Interventional Neurology.REFERENCES1 Engelter ST, Traenka C, Gensicke H, Schaedelin SA, Luft AR, Simonetti BG, Fischer U, Michel P, Sirimarco G, Kägi G, et al. Aspirin versus anticoagulation in cervical artery dissection (TREAT‐CAD): an open‐label, randomised, non‐inferiority trial. Lancet Neurol. 2021; 20:341–350. https://doi.org/10.1016/s1474‐4422(21)00044‐2CrossrefGoogle Scholar2 Markus HS, Levi C, King A, Madigan J, Norris J. 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. https://doi.org/10.1001/jamaneurol.2019.0072CrossrefGoogle Scholar3 Morimoto T, Crawford B, Wada K, Ueda S. Comparative efficacy and safety of novel oral anticoagulants in patients with atrial fibrillation: a network meta‐analysis with the adjustment for the possible bias from open label studies. J Cardiol. 2015; 66:466–474. https://doi.org/10.1016/j.jjcc.2015.05.018CrossrefMedlineGoogle Scholar4 Smith GC, Pell JP. Parachute use to prevent death and major trauma related to gravitational challenge: systematic review of randomised controlled trials. BMJ. 2003; 327:1459–1461. https://doi.org/10.1136/bmj.327.7429.1459CrossrefMedlineGoogle Scholar5 Caprio FZ, Bernstein RA, Alberts MJ, Curran Y, Bergman D, Korutz AW, Syed F, Ansari SA, Ansari SA, Prabhakaran S, et al. Efficacy and safety of novel oral anticoagulants in patients with cervical artery dissections. Cerebrovasc Dis. 2014; 38:247–253. https://doi.org/10.1159/000366265CrossrefGoogle Scholar6 Georgiadis D, Arnold M, von Buedingen HC, Valko P, Sarikaya H, Rousson V, Mattle HP, Bousser MG, Baumgartner RW. Aspirin vs anticoagulation in carotid artery dissection: a study of 298 patients. Neurology. 2009; 72:1810–1815. https://doi.org/10.1212/WNL.0b013e3181a2a50aCrossrefMedlineGoogle Scholar7 Touzé E, Gauvrit JY, Moulin T, Meder JF, Bracard S, Mas JL. Risk of stroke and recurrent dissection after a cervical artery dissection: a multicenter study. Neurology. 2003; 61:1347–1351. https://doi.org/10.1212/01.wnl.0000094325.95097.86CrossrefMedlineGoogle Scholar8 CADISS trial investigators ; Markus HS, Hayter E, Levi C, Feldman A, Venables G, Norris J. Antiplatelet treatment compared with anticoagulation treatment for cervical artery dissection (CADISS): a randomised trial. Lancet Neurol. 2015; 14:361–367. https://doi.org/10.1016/S1474‐4422(15)70018‐9Google Scholar9 McGuire LS, Ryoo JS, Hanjani SA, Atwal G, Charbel FT, Alaraj A. Impact of vessel narrowing and changes in blood flow on the development of ischemia in cervical arterial dissection using quantitative magnetic resonance angiography. Stroke Vasc Intv Neurol. 2022; 2:e000372. https://doi.org/10.1161/svin.122.000372Google Scholar10 Veltkamp R, Rizos T, Horstmann S. Intracerebral bleeding in patients on antithrombotic agents. Semin Thromb Hemost. 2013; 39:963–971. https://doi.org/10.1055/s‐0033‐1357506CrossrefMedlineGoogle Scholar11 Siegler JE. The attributable risk of nonstenotic cervical carotid plaque in cryptogenic stroke. Stroke Vasc Interv Neurol. 2023; 0:e000727. https://doi/10.1161/SVIN.122.000727Google Scholar12 Kleindorfer DO, Towfighi A, Chaturvedi S, Kevin MC, Jose G, Hill DL, Kamel H, Kernan WN,Kittner SJ, Liera EC, et al. Guideline for the prevention of stroke in patients with stroke and transient ischemic attack. A guideline from the American Heart Association/American Stroke Association. Stroke. 2021; 52:e364–e467. https://doi.org/10.1161/str.0000000000000375LinkGoogle Scholar13 Giossi A, Ritelli M, Costa P, Morotti A, Poli L, Del Zotto E, Volonghi I, Chiarelli N, Gamba MR, Bovi P. et al. Connective tissue anomalies in patients with spontaneous cervical artery dissection. Neurology. 2014; 83:2032–2037. https://doi.org/10.1212/wnl.0000000000001030CrossrefMedlineGoogle Scholar14 Raser JM, Mullen MT, Kasner SE, Cucchiara BL, Messé SR. Cervical carotid artery dissection is associated with styloid process length. Neurology. 2011; 77:2061–2066. https://doi.org/10.1212/WNL.0b013e31823b4729CrossrefMedlineGoogle Scholar15 Torikoshi S, Yamao Y, Ogino E, Taki W, Sunohara T, Nishimura M. A staged therapy for internal carotid artery dissection caused by vascular eagle syndrome. World Neurosurg. 2019; 129:133–139. https://doi.org/10.1016/j.wneu.2019.05.208CrossrefGoogle Scholar16 Jones J, Jones C, Nugent K. Vertebral artery dissection after a chiropractor neck manipulation. Proc (Bayl Univ Med Cent). 2015; 28:88–90. https://doi.org/10.1080/08998280.2015.11929202Google Scholar17 Liu Y, Li S, Wu Y, Wu F, Chang Y, Li H, Jia X, Saba L, Ji X, Yang Q. et al. The added value of vessel wall MRI in the detection of intraluminal thrombus in patients suspected of craniocervical artery dissection. Aging Dis. 2021; 12:2140–2150. https://doi.org/10.14336/AD.2021.0502Google Scholar eLetters(0)eLetters should relate to an article recently published in the journal and are not a forum for providing unpublished data. Comments are reviewed for appropriate use of tone and language. Comments are not peer-reviewed. Acceptable comments are posted to the journal website only. Comments are not published in an issue and are not indexed in PubMed. Comments should be no longer than 500 words and will only be posted online. References are limited to 10. Authors of the article cited in the comment will be invited to reply, as appropriate.Comments and feedback on AHA/ASA Scientific Statements and Guidelines should be directed to the AHA/ASA Manuscript Oversight Committee via its Correspondence page.Sign In to Submit a Response to This Article Previous Back to top Next FiguresReferencesRelatedDetails May 2023Vol 3, Issue 3 Article InformationMetrics © 2023 The Authors. Published on behalf of the American Heart Association, Inc., and the Society of Vascular and Interventional Neurology by Wiley Periodicals LLC.This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.https://doi.org/10.1161/SVIN.123.000841 Manuscript receivedJanuary 15, 2023Manuscript acceptedFebruary 1, 2023Originally publishedMay 2, 2023 Keywordscervical artery dissectionantithrombotic selectionmagnetic resonance imaging with angiographyPDF download