J Stroke.  2021 May;23(2):202-212. 10.5853/jos.2020.04273.

Management of Patients with Asymptomatic Carotid Stenosis May Need to Be Individualized: A Multidisciplinary Call for Action

• Paraskevas KI
• Mikhailidis DP
• Baradaran H
• Davies AH
• Eckstein HH
• Faggioli G
• Fernandes JFe
• Gupta A
• Jezovnik MK
• Kakkos SK
• Katsiki N
• Kooi ME
• Lanza G
• Liapis CD
• Loftus IM
• Millon A
• Nicolaides AN
• Poredos P
• Pini R
• Ricco JB
• Rundek T
• Saba L
• Spinelli F
• Stilo F
• Sultan S
• Zeebregts CJ
• Chaturvedi S

• KMID: 2516409
• DOI: http://doi.org/10.5853/jos.2020.04273

Abstract

The optimal management of patients with asymptomatic carotid stenosis (ACS) is the subject of extensive debate. According to the 2017 European Society for Vascular Surgery guidelines, carotid endarterectomy should (Class IIa; Level of Evidence: B) or carotid artery stenting may be considered (Class IIb; Level of Evidence: B) in the presence of one or more clinical/imaging characteristics that may be associated with an increased risk of late ipsilateral stroke (e.g., silent embolic infarcts on brain computed tomography/magnetic resonance imaging, progression in the severity of ACS, a history of contralateral transient ischemic attack/stroke, microemboli detection on transcranial Doppler, etc.), provided documented perioperative stroke/death rates are <3% and the patient’s life expectancy is >5 years. Besides these clinical/imaging characteristics, there are additional individual, ethnic/racial or social factors that should probably be evaluated in the decision process regarding the optimal management of these patients, such as individual patient needs/patient choice, patient compliance with best medical treatment, patient sex, culture, race/ethnicity, age and comorbidities, as well as improvements in imaging/operative techniques/outcomes. The present multispecialty position paper will present the rationale why the management of patients with ACS may need to be individualized.

Keyword

Endarterectomy, carotid; Carotid stenosis; Stroke; Ischemic attack, transient; Life expectancy; Patient preference

Reference

References

1. Virani SS, Alonso A, Benjamin EJ, Bittencourt MS, Callaway CW, Carson AP, et al. Heart disease and stroke statistics: 2020 update: a report from the American Heart Association. Circulation. 2020; 141:e139–e596.

2. Naylor AR, Ricco JB, de Borst GJ, Debus S, de Haro J, Halliday A, et al. Editor’s choice: management of atherosclerotic carotid and vertebral artery disease: 2017 clinical practice guidelines of the European Society for Vascular Surgery (ESVS). Eur J Vasc Endovasc Surg. 2018; 55:3–81.

3. Flaherty ML, Kissela B, Khoury JC, Alwell K, Moomaw CJ, Woo D, et al. Carotid artery stenosis as a cause of stroke. Neuroepidemiology. 2013; 40:36–41.

4. Keyhani S, Cheng EM, Hoggatt KJ, Austin PC, Madden E, Hebert PL, et al. Comparative effectiveness of carotid endarterectomy vs initial medical therapy in patients with asymptomatic carotid stenosis. JAMA Neurol. 2020; 77:1110–1121.

5. Paraskevas KI, Spence JD, Veith FJ, Nicolaides AN. Identifying which patients with asymptomatic carotid stenosis could benefit from intervention. Stroke. 2014; 45:3720–3724.

6. Nicolaides AN, Kakkos SK, Kyriacou E, Griffin M, Sabetai M, Thomas DJ, et al. Asymptomatic internal carotid artery stenosis and cerebrovascular risk stratification. J Vasc Surg. 2010; 52:1486–1496.

7. Kakkos SK, Griffin MB, Nicolaides AN, Kyriacou E, Sabetai MM, Tegos T, et al. The size of juxtaluminal hypoechoic area in ultrasound images of asymptomatic carotid plaques predicts the occurrence of stroke. J Vasc Surg. 2013; 57:609–618.

8. Stanisić M, Rzepa T. Attitude towards one’s illness vs. attitude towards a surgical operation, displayed by patients diagnosed with asymptomatic abdominal aortic aneurysm and asymptomatic internal carotid artery stenosis. Int Angiol. 2012; 31:376–385.

9. Xu J, Prince AE. Shared decision-making in vascular surgery. J Vasc Surg. 2019; 70:1711–1715.

10. Jayasooriya GS, Shalhoub J, Thapar A, Davies AH. Patient preference survey in the management of asymptomatic carotid stenosis. J Vasc Surg. 2011; 53:1466–1472.

11. Oddone EZ, Horner RD, Johnston DC, Stechuchak K, McIntyre L, Ward A, et al. Carotid endarterectomy and race: do clinical indications and patient preferences account for differences? Stroke. 2002; 33:2936–2943.

12. Brinjikji W, El-Sayed AM, Kallmes DF, Lanzino G, Cloft HJ. Racial and insurance based disparities in the treatment of carotid artery stenosis: a study of the Nationwide Inpatient Sample. J Neurointerv Surg. 2015; 7:695–702.

13. Egan BM, Li J, Qanungo S, Wolfman TE. Blood pressure and cholesterol control in hypertensive hypercholesterolemic patients: national health and nutrition examination surveys 1988-2010. Circulation. 2013; 128:29–41.

14. Zweifler RM, McClure LA, Howard VJ, Cushman M, Hovater MK, Safford MM, et al. Racial and geographic differences in prevalence, awareness, treatment and control of dyslipidemia: the reasons for geographic and racial differences in stroke (REGARDS) study. Neuroepidemiology. 2011; 37:39–44.

15. Gillespie CD, Hurvitz KA; Centers for Disease Control and Prevention (CDC). Prevalence of hypertension and controlled hypertension: United States, 2007-2010. MMWR Suppl. 2013; 62:144–148.

16. Halm EA, Tuhrim S, Wang JJ, Rockman C, Riles TS, Chassin MR. Risk factors for perioperative death and stroke after carotid endarterectomy: results of the New York carotid artery surgery study. Stroke. 2009; 40:221–229.

17. Brown HA, Sullivan MC, Gusberg RG, Dardik A, Sosa JA, Indes JE. Race as a predictor of morbidity, mortality, and neurologic events after carotid endarterectomy. J Vasc Surg. 2013; 57:1325–1330.

18. Dardik A, Bowman HM, Gordon TA, Hsieh G, Perler BA. Impact of race on the outcome of carotid endarterectomy: a population-based analysis of 9,842 recent elective procedures. Ann Surg. 2000; 232:704–709.

19. Nguyen LL, Henry AJ. Disparities in vascular surgery: is it biology or environment? J Vasc Surg. 2010; 51(4 Suppl):36S–41S.

20. Chaturvedi S, Madhavan R, Santhakumar S, Mehri-Basha M, Raje N. Higher risk factor burden and worse outcomes in urban carotid endarterectomy patients. Stroke. 2008; 39:2966–2968.

21. De Rango P, Lenti M, Simonte G, Cieri E, Giordano G, Caso V, et al. No benefit from carotid intervention in fatal stroke prevention for >80-year-old patients. Eur J Vasc Endovasc Surg. 2012; 44:252–259.

22. Rajamani K, Kennedy KF, Ruggiero NJ, Rosenfield K, Spertus J, Chaturvedi S. Outcomes of carotid endarterectomy in the elderly: report from the National Cardiovascular Data Registry. Stroke. 2013; 44:1172–1174.

23. Wach MM, Dumont TM, Shakir HJ, Snyder KV, Hopkins LN, Levy EI, et al. Carotid artery stenting in nonagenarians: are there benefits in surgically treating this high risk population? J Neurointerv Surg. 2015; 7:182–187.

24. Salomon du Mont L, Ravelojaona M, Puyraveau M, Al Sayed M, Ritucci E, Rinckenbach S. Carotid endarterectomy in octogenarian: short- and midterm results. Ann Vasc Surg. 2014; 28:917–923.

25. Schmid S, Tsantilas P, Knappich C, Kallmayer M, König T, Breitkreuz T, et al. Risk of inhospital stroke or death is associated with age but not sex in patients treated with carotid endarterectomy for asymptomatic or symptomatic stenosis in routine practice: secondary data analysis of the nationwide german statutory quality assurance database from 2009 to 2014. J Am Heart Assoc. 2017; 6:e004764.

26. Hobbs LK, Ramdon A, Roddy SP, Hnath JC, Yeh CC, Darling RC 3rd. Outcomes for carotid endarterectomy in nonagenarians. J Vasc Surg. 2020; 71:96–103.

27. Rinckenbach V, Rinckenbach S, Thaveau F, Hassani O, Hedelin G, Chakfé N, et al. Mortality and morbidity of consecutive surgical carotid revascularisations in octogenarians. J Mal Vasc. 2007; 32:192–200.

28. Naylor AR. Time to rethink management strategies in asymptomatic carotid artery disease. Nat Rev Cardiol. 2011; 9:116–124.

29. Halliday A, Mansfield A, Marro J, Peto C, Peto R, Potter J, et al. Prevention of disabling and fatal strokes by successful carotid endarterectomy in patients without recent neurological symptoms: randomised controlled trial. Lancet. 2004; 363:1491–1502.

30. Melin AA, Schmid KK, Lynch TG, Pipinos II, Kappes S, Longo GM, et al. Preoperative frailty Risk Analysis Index to stratify patients undergoing carotid endarterectomy. J Vasc Surg. 2015; 61:683–689.

31. Pandit V, Lee A, Zeeshan M, Goshima K, Tan TW, Jhajj S, et al. Effect of frailty syndrome on the outcomes of patients with carotid stenosis. J Vasc Surg. 2020; 71:1595–1600.

32. Executive Committee for the Asymptomatic Carotid Atherosclerosis Study. Endarterectomy for asymptomatic carotid artery stenosis. JAMA. 1995; 273:1421–1428.

33. Jalbert JJ, Nguyen LL, Gerhard-Herman MD, Jaff MR, White CJ, Rothman AT, et al. Outcomes after carotid artery stenting in medicare beneficiaries, 2005 to 2009. JAMA Neurol. 2015; 72:276–286.

34. Rothwell PM, Goldstein LB. Carotid endarterectomy for asymptomatic carotid stenosis: asymptomatic carotid surgery trial. Stroke. 2004; 35:2425–2427.

35. Madsen TE, Khoury J, Alwell K, Moomaw CJ, Rademacher E, Flaherty ML, et al. Sex-specific stroke incidence over time in the Greater Cincinnati/Northern Kentucky Stroke Study. Neurology. 2017; 89:990–996.

36. Hellings WE, Pasterkamp G, Verhoeven BA, De Kleijn DP, De Vries JP, Seldenrijk KA, et al. Gender-associated differences in plaque phenotype of patients undergoing carotid endarterectomy. J Vasc Surg. 2007; 45:289–297.

37. Phan HT, Reeves MJ, Blizzard CL, Thrift AG, Cadilhac DA, Sturm J, et al. Sex differences in severity of stroke in the INSTRUCT study: a meta-analysis of individual participant data. J Am Heart Assoc. 2019; 8:e010235.

38. Ota H, Reeves MJ, Zhu DC, Majid A, Collar A, Yuan C, et al. Sex differences in patients with asymptomatic carotid atherosclerotic plaque: in vivo 3.0-T magnetic resonance study. Stroke. 2010; 41:1630–1635.

39. De Rango P, Brown MM, Leys D, Howard VJ, Moore WS, Paciaroni M, et al. Management of carotid stenosis in women: consensus document. Neurology. 2013; 80:2258–2268.

40. Halliday A, Harrison M, Hayter E, Kong X, Mansfield A, Marro J, et al. 10-Year stroke prevention after successful carotid endarterectomy for asymptomatic stenosis (ACST-1): a multicentre randomised trial. Lancet. 2010; 376:1074–1084.

41. Rothwell PM. ACST: which subgroups will benefit most from carotid endarterectomy? Lancet. 2004; 364:1122–1123.

42. Dansey KD, Pothof AB, Zettervall SL, Swerdlow NJ, Liang P, Schneider JR, et al. Clinical impact of sex on carotid revascularization. J Vasc Surg. 2020; 71:1587–1594.

43. Almaaitah S, Ciemins EL, Joshi V, Arora A, Meskow C, Rothberg MB. Variation in patient smoking cessation rates among health-care providers: an observational study. Chest. 2020; 158:2038–2046.

44. McHugh SM, Eisenberg N, Montbriand J, Roche-Nagle G. Smoking cessation rates among patients undergoing vascular surgery in a Canadian center. Ann Vasc Surg. 2017; 45:138–143.

45. Banach M, Mikhailidis DP. Statin intolerance: some practical hints. Cardiol Clin. 2018; 36:225–231.

46. Paraskevas KI, Mikhailidis DP, Veith FJ. Optimal statin type and dosage for vascular patients. J Vasc Surg. 2011; 53:837–844.

47. Alakbarzade V, Huang X, Ster IC, McEntagart M, Pereira AC. High on-clopidogrel platelet reactivity in ischaemic stroke or transient ischaemic attack: systematic review and meta-analysis. J Stroke Cerebrovasc Dis. 2020; 29:104877.

48. Paraskevas KI, de Borst GJ, Veith FJ. Why randomized controlled trials do not always reflect reality. J Vasc Surg. 2019; 70:607–614.

49. Conrad MF, Boulom V, Mukhopadhyay S, Garg A, Patel VI, Cambria RP. Progression of asymptomatic carotid stenosis despite optimal medical therapy. J Vasc Surg. 2013; 58:128–135.

50. Kakkos SK, Nicolaides AN, Charalambous I, Thomas D, Giannopoulos A, Naylor AR, et al. Predictors and clinical significance of progression or regression of asymptomatic carotid stenosis. J Vasc Surg. 2014; 59:956–967.

51. Yang B, Ma Y, Wang T, Chen Y, Wang Y, Zhao Z, et al. Carotid endarterectomy and stenting in a Chinese population: safety outcome of the revascularization of extracranial carotid artery stenosis trial. Transl Stroke Res. 2021; 12:239–247.

52. Klarin D, Cambria RP, Ergul EA, Silverman SB, Patel VI, LaMuraglia GM, et al. Risk factor profile and anatomic features of previously asymptomatic patients presenting with carotid-related stroke. J Vasc Surg. 2018; 68:1390–1395.

53. Saba L, Moody AR, Saam T, Kooi ME, Wasserman BA, Staub D, et al. Vessel wall-imaging biomarkers of carotid plaque vulnerability in stroke prevention trials: a viewpoint from the Carotid Imaging Consensus Group. JACC Cardiovasc Imaging. 2020; 13:2445–2456.

54. Lanza G, Setacci C, Ricci S, Castelli P, Cremonesi A, Lanza J, et al. An update of the Italian Stroke Organization: Stroke Prevention Awareness Diffusion Group guidelines on carotid endarterectomy and stenting: a personalized medicine approach. Int J Stroke. 2017; 12:560–567.

55. Lanza G, Giannandrea D, Lanza J, Ricci S, Gensini GF. Personalized-medicine on carotid endarterectomy and stenting. Ann Transl Med. 2020; 8:1274.

56. Saba L, Yuan C, Hatsukami TS, Balu N, Qiao Y, DeMarco JK, et al. Carotid artery wall imaging: perspective and guidelines from the ASNR vessel wall imaging study group and expert consensus recommendations of the American Society of Neuroradiology. AJNR Am J Neuroradiol. 2018; 39:E9–E31.

57. Schindler A, Schinner R, Altaf N, Hosseini AA, Simpson RJ, Esposito-Bauer L, et al. Prediction of stroke risk by detection of hemorrhage in carotid plaques: meta-analysis of individual patient data. JACC Cardiovasc Imaging. 2020; 13(2 Pt 1):395–406.

58. Vikatmaa P, Mitchell D, Jensen LP, Beiles B, Björck M, Halbakken E, et al. Variation in clinical practice in carotid surgery in nine countries 2005-2010: lessons from VASCUNET and recommendations for the future of national clinical audit. Eur J Vasc Endovasc Surg. 2012; 44:11–17.

59. Kragsterman B, Björck M, Lindbäck J, Bergqvist D, Pärsson H; Swedish Vascular Registry (Swedvasc). Long-term survival after carotid endarterectomy for asymptomatic stenosis. Stroke. 2006; 37:2886–2891.

60. Ballotta E, Meneghetti G, Manara R, Baracchini C. Long-term survival and stroke-free survival after eversion carotid endarterectomy for asymptomatic severe carotid stenosis. J Vasc Surg. 2007; 46:265–270.

61. Alcocer F, Mujib M, Lowman B, Patterson MA, Passman MA, Matthews TC, et al. Risk scoring system to predict 3-year survival in patients treated for asymptomatic carotid stenosis. J Vasc Surg. 2013; 57:1576–1580.

62. Conrad MF, Kang J, Mukhopadhyay S, Patel VI, LaMuraglia GM, Cambria RP. A risk prediction model for determining appropriateness of CEA in patients with asymptomatic carotid artery stenosis. Ann Surg. 2013; 258:534–540.

63. Wallaert JB, Cronenwett JL, Bertges DJ, Schanzer A, Nolan BW, De Martino R, et al. Optimal selection of asymptomatic patients for carotid endarterectomy based on predicted 5-year survival. J Vasc Surg. 2013; 58:112–118.

64. Gupta PK, Ramanan B, Mactaggart JN, Sundaram A, Fang X, Gupta H, et al. Risk index for predicting perioperative stroke, myocardial infarction, or death risk in asymptomatic patients undergoing carotid endarterectomy. J Vasc Surg. 2013; 57:318–326.

65. Wallaert JB, Newhall KA, Suckow BD, Brooke BS, Zhang M, Farber AE, et al. Relationships between 2-year survival, costs, and outcomes following carotid endarterectomy in asymptomatic patients in the Vascular Quality Initiative. Ann Vasc Surg. 2016; 35:174–182.

66. Cooper M, Arhuidese IJ, Obeid T, Hicks CW, Canner J, Malas MB. Perioperative and long-term outcomes after carotid endarterectomy in hemodialysis patients. JAMA Surg. 2016; 151:947–952.

67. DeMartino RR, Brooke BS, Neal D, Beck AW, Conrad MF, Arya S, et al. Development of a validated model to predict 30-day stroke and 1-year survival after carotid endarterectomy for asymptomatic stenosis using the Vascular Quality Initiative. J Vasc Surg. 2017; 66:433–444.

68. Morales-Gisbert SM, Zaragozá García JM, Plaza Martínez Á, Gómez Palonés FJ, Ortiz-Monzón E. Development of an individualized scoring system to predict mid-term survival after carotid endarterectomy. J Cardiovasc Surg (Torino). 2017; 58:535–542.

69. Carmo M, Barbetta I, Bissacco D, Trimarchi S, Catanese V, Bonzini M, et al. Development and validation of a score to predict life expectancy after carotid endarterectomy in asymptomatic patients. J Vasc Surg. 2018; 67:175–182.

70. Keyhani S, Madden E, Cheng EM, Bravata DM, Halm E, Austin PC, et al. Risk prediction tools to improve patient selection for carotid endarterectomy among patients with asymptomatic carotid stenosis. JAMA Surg. 2019; 154:336–344.

71. Dasenbrock HH, Smith TR, Gormley WB, Castlen JP, Patel NJ, Frerichs KU, et al. Predictive score of adverse events after carotid endarterectomy: the NSQIP Registry Carotid Endarterectomy Scale. J Am Heart Assoc. 2019; 8:e013412.

72. Veith FJ, Bell PR. How many of you can read but still not see? A comment on a recent review of carotid guidelines. Eur J Vasc Endovasc Surg. 2016; 51:471–472.

73. Howard VJ, Meschia JF, Lal BK, Turan TN, Roubin GS, Brown RD Jr, et al. Carotid revascularization and medical management for asymptomatic carotid stenosis: protocol of the CREST-2 clinical trials. Int J Stroke. 2017; 12:770–778.

74. 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; 21:1–40.

75. Giannopoulos A, Kakkos S, Abbott A, Naylor AR, Richards T, Mikhailidis DP, et al. Long-term mortality in patients with asymptomatic carotid stenosis: implications for statin therapy. Eur J Vasc Endovasc Surg. 2015; 50:573–582.

76. Saba L, Saam T, Jäger HR, Yuan C, Hatsukami TS, Saloner D, et al. Imaging biomarkers of vulnerable carotid plaques for stroke risk prediction and their potential clinical implications. Lancet Neurol. 2019; 18:559–572.