Current Medical and Surgical Stroke Prevention Therapies for Patients with Carotid Artery Stenosis

Author(s): Mirza Jusufovic*, Karolina Skagen, Kirsten Krohg-Sørensen, Mona Skjelland

Journal Name: Current Neurovascular Research

Volume 16 , Issue 1 , 2019

Become EABM
Become Reviewer


Carotid Artery Stenosis (CAS) is a marker of systemic atherosclerosis and patients with CAS are at high risk of vascular events in multiple vascular locations, including ipsilateral ischemic stroke. Both medical and surgical therapies have been demonstrated effective in reducing this risk. The optimal management for patients with asymptomatic carotid artery stenosis remains controversial. In patients with symptomatic CAS ≥70%, CEA has been demonstrated to reduce the risk of stroke. With the risk of recurrent stroke being particularly high in the first 2 weeks after the first event, Carotid Endarterectomy (CEA) or carotid angioplasty with stenting provides maximal benefits to patients with symptomatic CAS ≥70% if performed within this «2-week» target. Several large ongoing trials are currently comparing the risks and benefits of carotid revascularization versus medical therapy alone.

Keywords: Carotid artery stenosis, clinical trials, stroke, cardiovascular risk, prevention, carotid endarterectomy, carotid stenting.

Inzitari D, Eliasziw M, Gates P, et al. The causes and risk of stroke in patients with asymptomatic internal-carotid-artery stenosis. North American symptomatic carotid endarterectomy trial collaborators. N Engl J Med 2000; 342(23): 1693-700.
Barnett HJ, Gunton RW, Eliasziw M, et al. Causes and severity of ischemic stroke in patients with internal carotid artery stenosis. JAMA 2000; 283(11): 1429-36.
Brott TG, Halperin JL, Abbara S, et al. 2011 ASA/ACCF/AHA/ AANN/AANS/ACR/ASNR/CNS/SAIP/SCAI/SIR/SNIS/SVM/SVS guideline on the management of patients with extracranial carotid and vertebral artery disease: executive summary. A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, and the American Stroke Association, American Association of Neuroscience Nurses, American Association of Neurological Surgeons, American College of Radiology, American Society of Neuroradiology, Congress of Neurological Surgeons, Society of Atherosclerosis Imaging and Prevention, Society for Cardiovascular Angiography and Interventions, Society of Interventional Radiology, Society of NeuroInterventional Surgery, Society for Vascular Medicine, and Society for Vascular Surgery. Circulation 2011; 124(4): 489-532.
Alonso-Coello P, Bellmunt S, McGorrian C, et al. Antithrombotic therapy in peripheral artery disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141(2 Suppl): e669S-90S.
Meschia JF, Bushnell C, Boden-Albala B, et al. Guidelines for the primary prevention of stroke: A statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2014; 45(12): 3754-832.
Ricotta JJ, Aburahma A, Ascher E, et al. Updated society for vascular surgery guidelines for management of extracranial carotid disease: Executive summary. J Vasc Surg 2011; 54(3): 832-6.
Stone NJ, Robinson JG, Lichtenstein AH, et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 2014; 129(25)(Suppl. 2): S1-S45.
Aboyans V, Ricco JB, Bartelink MEL, et al. 2017 ESC Guidelines on the diagnosis and treatment of peripheral arterial diseases, in collaboration with the European Society for Vascular Surgery (ESVS): Document covering atherosclerotic disease of extracranial carotid and vertebral, mesenteric, renal, upper and lower extremity arteriesEndorsed by: The European Stroke Organization (ESO) the task force for the diagnosis and treatment of peripheral arterial diseases of the European Society of Cardiology (ESC) and of the European Society for Vascular Surgery (ESVS). Eur Heart J 2018; 39(9): 763-816.
Ahmed N, Steiner T, Caso V, Wahlgren N. participants E-Ks. Recommendations from the ESO-Karolinska stroke update conference, stockholm 13-15 November 2016. Eur Stroke J 2017; 2(2): 95-102.
Mancia G, Fagard R, Narkiewicz K, et al. 2013 ESH/ESC Guidelines for the management of arterial hypertension: The task force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J Hypertens 2013; 31(7): 1281-357.
MRC European Carotid Surgery Trial: Interim results for symptomatic patients with severe (70-99%) or with mild (0-29%) carotid stenosis. European Carotid Surgery Trialists’ Collaborative Group. Lancet 1991; 337(8752): 1235-43.
North American Symptomatic Carotid Endarterectomy Trial Collaborators, Barnett HJM, Taylor DW, Haynes RB, Sackett DL, Peerless SJ, Ferguson GG, Fox AJ, Rankin RN, Hachinski VC, Wiebers DO, Eliasziw M. Beneficial effect of carotid endarterectomy in symptomatic patients with high-grade carotid stenosis. N Engl J Med 1991; 325(7): 445-53.
Halliday A, Mansfield A, Marro J, et al. Prevention of disabling and fatal strokes by successful carotid endarterectomy in patients without recent neurological symptoms: Randomised controlled trial. Lancet 2004; 363(9420): 1491-502.
Abbott AL. Medical (nonsurgical) intervention alone is now best for prevention of stroke associated with asymptomatic severe carotid stenosis: Results of a systematic review and analysis. Stroke 2009; 40(10): e573-83.
Spence JD. Management of asymptomatic carotid stenosis. Neurol Clin 2015; 33(2): 443-57.
Chambers BR, Norris JW. Outcome in patients with asymptomatic neck bruits. N Engl J Med 1986; 315(14): 860-5.
Chambers BR, Donnan GA. Carotid endarterectomy for asymptomatic carotid stenosis. Cochrane Database Syst Rev 2005; (4): CD001923.
Cote R, Battista RN, Abrahamowicz M, Langlois Y, Bourque F, Mackey A. Lack of effect of aspirin in asymptomatic patients with carotid bruits and substantial carotid narrowing. The asymptomatic cervical bruit study group. Ann Intern Med 1995; 123(9): 649-55.
Hobson RW, 2nd, Krupski WC, Weiss DG. Influence of aspirin in the management of asymptomatic carotid artery stenosis. VA cooperative study group on asymptomatic carotid stenosis. J Vasc Surg 1993; 17(2): 257-63. discussion 63-5.
Antithrombotic Trialists C. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ 2002; 324(7329): 71-86.
King A, Shipley M, Markus H, Investigators A. The effect of medical treatments on stroke risk in asymptomatic carotid stenosis. Stroke 2013; 44(2): 542-6.
Constantinou J, Jayia P, Hamilton G. Best evidence for medical therapy for carotid artery stenosis. J Vasc Surg 2013; 58(4): 1129-39.
Juhola J, Magnussen CG, Berenson GS, et al. Combined effects of child and adult elevated blood pressure on subclinical atherosclerosis: The International Childhood Cardiovascular Cohort Consortium. Circulation 2013; 128(3): 217-24.
Group PC. Randomised trial of a perindopril-based blood-pressure-lowering regimen among 6,105 individuals with previous stroke or transient ischaemic attack. Lancet 2001; 358(9287): 1033-41.
Neal B, MacMahon S, Chapman N. Blood Pressure Lowering Treatment Trialists C. Effects of ACE inhibitors, calcium antagonists, and other blood-pressure-lowering drugs: Results of prospectively designed overviews of randomised trials. Blood Pressure Lowering Treatment Trialists’. Collaboration Lancet 2000; 356(9246): 1955-64.
Sare GM, Gray LJ, Wardlaw J, Chen C, Bath PM, Investigators ET. Is lowering blood pressure hazardous in patients with significant ipsilateral carotid stenosis and acute ischaemic stroke? Interim assessment in the ‘Efficacy of Nitric Oxide in Stroke’ trial. Blood Press Monit 2009; 14(1): 20-5.
Liapis CD, Kakisis JD, Kostakis AG. Carotid stenosis: Factors affecting symptomatology. Stroke 2001; 32(12): 2782-6.
Tropeano AI, Saleh N, Hawajri N, Macquin-Mavier I, Maison P. Do all antihypertensive drugs improve carotid intima-media thickness? A network meta-analysis of randomized controlled trials. Fundam Clin Pharmacol 2011; 25(3): 395-404.
Wang JG, Staessen JA, Li Y, et al. Carotid intima-media thickness and antihypertensive treatment: A meta-analysis of randomized controlled trials. Stroke 2006; 37(7): 1933-40.
Sillesen H. What does ‘best medical therapy’ really mean? Eur J Vasc Endovasc Surg 2008; 35(2): 139-44.
Group SR, Wright JT Jr, Williamson JD, et al. A randomized trial of intensive versus standard blood-pressure control. N Engl J Med 2015; 373(22): 2103-16.
Taylor F, Huffman MD, Macedo AF, et al. Statins for the primary prevention of cardiovascular disease. Cochrane Database Syst Rev 2013; 2013(1): CD004816.
Tattersall MC, Gassett A, Korcarz CE, et al. Predictors of carotid thickness and plaque progression during a decade: The Multi-Ethnic Study of Atherosclerosis. Stroke 2014; 45(11): 3257-62.
Heart Protection Study Collaborative G. MRC/BHF Heart protection study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: A randomised placebo-controlled trial. Lancet 2002; 360(9326): 7-22.
Ridker PM, Danielson E, Fonseca FA, et al. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med 2008; 359(21): 2195-207.
Collins R, Reith C, Emberson J, et al. Interpretation of the evidence for the efficacy and safety of statin therapy. Lancet 2016; 388(10059): 2532-61.
Action to Control Cardiovascular Risk in Diabetes Study G Gerstein HC, Miller ME, etal Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med 2008; 358(24): 2545-59.
Group AC, Patel A, MacMahon S, et al. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med 2008; 358(24): 2560-72.
AbuRahma AF, Srivastava M, Stone PA, et al. Effect of statins on early and late clinical outcomes of carotid endarterectomy and the rate of post-carotid endarterectomy restenosis. J Am Coll Surg 2015; 220(4): 481-7.
Rothwell PM, Goldstein LB. Carotid endarterectomy for asymptomatic carotid stenosis: Asymptomatic carotid surgery trial. Stroke 2004; 35(10): 2425-7.
Goldstein LB, Samsa GP, Matchar DB, Oddone EZ. Multicenter review of preoperative risk factors for endarterectomy for asymptomatic carotid artery stenosis. Stroke 1998; 29(4): 750-3.
Brott TG, Hobson RW II, Howard G, et al. Stenting versus endarterectomy for treatment of carotid-artery stenosis. N Engl J Med 2010; 363(1): 11-23.
Yadav JS, Wholey MH, Kuntz RE, et al. Protected carotid-artery stenting versus endarterectomy in high-risk patients. N Engl J Med 2004; 351(15): 1493-501.
Sardar P, Chatterjee S, Aronow HD, et al. Carotid artery stenting versus endarterectomy for stroke prevention: A meta-analysis of clinical trials. J Am Coll Cardiol 2017; 69(18): 2266-75.
Committee CS. A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). CAPRIE Steering Committee. Lancet 1996; 348(9038): 1329-39.
Group ES, Halkes PH, van Gijn J, Kappelle LJ, Koudstaal PJ, Algra A. Aspirin plus dipyridamole versus aspirin alone after cerebral ischaemia of arterial origin (ESPRIT): Randomised controlled trial. Lancet 2006; 367(9523): 1665-73.
Sacco RL, Diener HC, Yusuf S, et al. Aspirin and extended-release dipyridamole versus clopidogrel for recurrent stroke. N Engl J Med 2008; 359(12): 1238-51.
Markus HS, Droste DW, Kaps M, et al. Dual antiplatelet therapy with clopidogrel and aspirin in symptomatic carotid stenosis evaluated using doppler embolic signal detection: the Clopidogrel and Aspirin for Reduction of Emboli in Symptomatic Carotid Stenosis (CARESS) trial. Circulation 2005; 111(17): 2233-40.
Wang Y, Wang Y, Zhao X, et al. Clopidogrel with aspirin in acute minor stroke or transient ischemic attack. N Engl J Med 2013; 369(1): 11-9.
Engelter S, Lyrer P. Antiplatelet therapy for preventing stroke and other vascular events after carotid endarterectomy. Cochrane Database Syst Rev 2003; 2003(3): CD001458.
Dalainas I, Nano G, Bianchi P, Stegher S, Malacrida G, Tealdi DG. Dual antiplatelet regime versus acetyl-acetic acid for carotid artery stenting. Cardiovasc Intervent Radiol 2006; 29(4): 519-21.
McKevitt FM, Randall MS, Cleveland TJ, Gaines PA, Tan KT, Venables GS. The benefits of combined anti-platelet treatment in carotid artery stenting. Eur J Vasc Endovasc Surg 2005; 29(5): 522-7.
Patti G, Tomai F, Melfi R, et al. Strategies of clopidogrel load and atorvastatin reload to prevent ischemic cerebral events in patients undergoing protected carotid stenting. Results of the randomized ARMYDA-9 CAROTID (Clopidogrel and Atorvastatin Treatment During Carotid Artery Stenting) study. J Am Coll Cardiol 2013; 61(13): 1379-87.
Gensicke H, van der Worp HB, Nederkoorn PJ, et al. Ischemic brain lesions after carotid artery stenting increase future cerebrovascular risk. J Am Coll Cardiol 2015; 65(6): 521-9.
Silvestrini M, Vernieri F, Pasqualetti P, et al. Impaired cerebral vasoreactivity and risk of stroke in patients with asymptomatic carotid artery stenosis. JAMA 2000; 283(16): 2122-7.
Blaser T, Hofmann K, Buerger T, Effenberger O, Wallesch CW, Goertler M. Risk of stroke, transient ischemic attack, and vessel occlusion before endarterectomy in patients with symptomatic severe carotid stenosis. Stroke 2002; 33(4): 1057-62.
Rothwell PM, Howard SC, Spence JD. Carotid Endarterectomy Trialists C. Relationship between blood pressure and stroke risk in patients with symptomatic carotid occlusive disease. Stroke 2003; 34(11): 2583-90.
Amarenco P, Bogousslavsky J, Callahan A III, et al. High-dose atorvastatin after stroke or transient ischemic attack. N Engl J Med 2006; 355(6): 549-59.
Sillesen H, Amarenco P, Hennerici MG, et al. Atorvastatin reduces the risk of cardiovascular events in patients with carotid atherosclerosis: A secondary analysis of the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial. Stroke 2008; 39(12): 3297-302.
Crisby M, Nordin-Fredriksson G, Shah PK, Yano J, Zhu J, Nilsson J. Pravastatin treatment increases collagen content and decreases lipid content, inflammation, metalloproteinases, and cell death in human carotid plaques: implications for plaque stabilization. Circulation 2001; 103(7): 926-33.
Kadoglou NP, Sailer N, Moumtzouoglou A, Kapelouzou A, Gerasimidis T, Liapis CD. Aggressive lipid-lowering is more effective than moderate lipid-lowering treatment in carotid plaque stabilization. J Vasc Surg 2010; 51(1): 114-21.
Reiff T, Amiri H, Rohde S, Hacke W, Ringleb PA. Statins reduce peri-procedural complications in carotid stenting. Eur J Vasc Endovasc Surg 2014; 48(6): 626-32.
Randomised trial of endarterectomy for recently symptomatic carotid stenosis: Final results of the MRC European Carotid Surgery Trial (ECST). Lancet 1998; 351(9113): 1379-87.
Rerkasem K, Rothwell PM. Carotid endarterectomy for symptomatic carotid stenosis. Cochrane Database Syst Rev 2011; 2011(4): CD001081.
Rothwell PM, Eliasziw M, Gutnikov SA, Warlow CP, Barnett HJ. Carotid Endarterectomy Trialists C. Endarterectomy for symptomatic carotid stenosis in relation to clinical subgroups and timing of surgery. Lancet 2004; 363(9413): 915-24.
Alamowitch S, Eliasziw M, Barnett HJ. North American Symptomatic Carotid Endarterectomy T, Group ASAT, Carotid Endarterectomy Trial G. The risk and benefit of endarterectomy in women with symptomatic internal carotid artery disease. Stroke 2005; 36(1): 27-31.
Marulanda-Londono E, Chaturvedi S. Carotid stenosis in women: time for a reappraisal. Stroke Vasc Neurol 2016; 1(4): 192-6.
Kastrup A, Groschel K. Carotid endarterectomy versus carotid stenting: An updated review of randomized trials and subgroup analyses. Acta Chir Belg 2007; 107(2): 119-28.
Kastrup A, Nagele T, Groschel K, et al. Incidence of new brain lesions after carotid stenting with and without cerebral protection. Stroke 2006; 37(9): 2312-6.
Van Damme H, Limet R. Lessons learnt from carotid artery trials. Acta Chir Belg 2006; 106(5): 489-99.
Bonati LH, Jongen LM, Haller S, et al. New ischaemic brain lesions on MRI after stenting or endarterectomy for symptomatic carotid stenosis: A substudy of the International Carotid Stenting Study (ICSS). Lancet Neurol 2010; 9(4): 353-62.
Bonati LH, Dobson J, Featherstone RL, et al. Long-term outcomes after stenting versus endarterectomy for treatment of symptomatic carotid stenosis: The International Carotid Stenting Study (ICSS) randomised trial. Lancet 2015; 385(9967): 529-38.
Brott TG, Howard G, Roubin GS, et al. Long-term results of stenting versus endarterectomy for carotidartery stenosis. N Engl J Med 2016; 374(11): 1021-31.
Voeks JH, Howard G, Roubin GS, et al. Age and outcomes after carotid stenting and endarterectomy: The carotid revascularization endarterectomy versus stenting trial. Stroke 2011; 42(12): 3484-90.
Giannopoulos S, Texakalidis P, Jonnalagadda AK, Karasavvidis T, Giannopoulos S, Kokkinidis DG. Revascularization of radiationinduced carotid artery stenosis with carotid endarterectomy vs. carotid artery stenting: A systematic review and meta-analysis. Cardiovasc Revasc Med 2018; 19(5 PtB): 638-44.
Howard VJ, Meschia JF, Lal BK, et al. Carotid revascularization and medical management for asymptomatic carotid stenosis: Protocol of the CREST-2 clinical trials. Int J Stroke 2017; 12(7): 770-8.
Bulbulia R, Halliday A. The Asymptomatic Carotid Surgery Trial-2 (ACST-2): An ongoing randomised controlled trial comparing carotid endarterectomy with carotid artery stenting to prevent stroke. Health Technol Assess 2017; 21(57): 1-40.

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2019
Published on: 13 May, 2019
Page: [96 - 103]
Pages: 8
DOI: 10.2174/1567202616666190131162811
Price: $65

Article Metrics

PDF: 71
PRC: 1