Advertisement

Medical Therapy for Carotid and Vertebral Artery Stenosis

  • Moayd M. Alkhalifah
  • Paul M. Gadient
  • Seemant Chaturvedi
Chapter

Abstract

All patients with evidence of internal carotid artery or vertebral artery atherosclerotic disease should be treated with medical therapy to stabilize and hopefully prevent the progression of the atherosclerotic disease process. In practice, this includes several facets. This includes antithrombotic therapies to prevent thrombus formation and the subsequent risk of transient ischemic attack or ischemic stroke. In addition, cholesterol lowering with statin medication is recommended to help prevent disease progression. Blood pressure control is also important to retard ongoing vascular injury. Lifestyle modification such as smoking cessation and increased physical activity is also recommended.

In this chapter, we shall outline the rationale and evidence for these therapies in patients with carotid atherosclerosis. In addition, modern clinical trials that are testing aggressive medical management for carotid artery stenosis will be discussed.

Keywords

Carotid stenosis Atherosclerosis Hypertension Aspirin Antiplatelet therapy Statins Hyperlipidemia 

Abbreviations

CHANCE

Clopidogrel in High-Risk Patients With Acute Nondisabling Events

CREST-2

Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis Study

ECST

European Carotid Surgery Trial

EPOCH-CAS

Effect of pitavastatin on preventing ischemic complications with carotid artery stenting

ESPRIT

European/Australasian Stroke Prevention in Reversible Ischemia Trial

ESPS2

European Stroke Prevention Study 2

LIPID

Long-term Intervention with Pravastatin in Ischemic Disease

mRS

Modified Rankin Scale

NASCET

North American Symptomatic Carotid Endarterectomy Trial

NIHSS

National Institutes of Health Stroke Scale

PRoFESS

Prevention Regimen for Effectively Avoiding Second Strokes

SAMMPRIS

Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis

SMART

Second Manifestations of ARTerial disease

SOCRATES

Acute Stroke or Transient Ischemic Attack Treated with Aspirin or Ticagrelor and Patient Outcomes

SPARCL

Stroke Prevention by Aggressive Reduction in Cholesterol Levels

VISSIT

Vitesse Stent Ischemic Therapy

WASID

Warfarin-Aspirin for Symptomatic Intracranial Disease

References

  1. 1.
    Kernan WN, Ovbiagele B, Black HR, et al. Guidelines for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2014;45:2160–236.CrossRefPubMedGoogle Scholar
  2. 2.
    Barnett HJM, Taylor DW, Eliasziw M, et al. Benefit of carotid endarterectomy in patients with symptomatic moderate or severe stenosis. N Engl J Med. 1998;339:1415–25.CrossRefPubMedGoogle Scholar
  3. 3.
    Rothwell PM, Eliasziw M, Gutnikov SA, et al. Analysis of pooled data from the randomised controlled trials of endarterectomy for symptomatic carotid stenosis. Lancet. 2003;361:107–16.CrossRefPubMedGoogle Scholar
  4. 4.
    Wang Y, Wang Y, Zhao X, et al. Clopidogrel with aspirin in acute minor stroke or transient ischemic attack. N Engl J Med. 2013;369:11–9.CrossRefPubMedGoogle Scholar
  5. 5.
    Diener HC, Cunha L, Forbes C, et al. European Stroke Prevention Study 2. Dipyridamole and acetylsalicylic acid in the secondary prevention of stroke. J Neurol Sci. 1996;143:1–13.CrossRefPubMedGoogle Scholar
  6. 6.
    The Esprit Study Group. Aspirin plus dipyridamole versus aspirin alone after cerebral ischaemia of arterial origin (ESPRIT): randomised controlled trial. Lancet. 2006;367:1665–73.CrossRefGoogle Scholar
  7. 7.
    Sacco RL, Diener H-C, Yusuf S, et al. Aspirin and extended-release dipyridamole versus clopidogrel for recurrent stroke. N Engl J Med. 2008;359:1238–51.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    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;111:2233–40.CrossRefPubMedGoogle Scholar
  9. 9.
    Johnston SC, Amarenco P, Albers GW, et al. Ticagrelor versus aspirin in acute stroke or transient ischemic attack. N Engl J Med. 2016;375:35–43.CrossRefPubMedGoogle Scholar
  10. 10.
    Amarenco P, Albers GW, Denison H, et al. Efficacy and safety of ticagrelor versus aspirin in acute stroke or transient ischaemic attack of atherosclerotic origin: a subgroup analysis of SOCRATES, a randomised, double-blind, controlled trial. Lancet Neurol. 2017;16:301–10.CrossRefPubMedGoogle Scholar
  11. 11.
    Taylor DW, Barnett HJM, Haynes RB, et al. Low-dose and high-dose acetylsalicylic acid for patients undergoing carotid endarterectomy: a randomised controlled trial. Lancet. 1999;353:2179–84.CrossRefPubMedGoogle Scholar
  12. 12.
    Chaturvedi S, Bruno A, Feasby T, et al. Carotid endarterectomy—an evidence-based review: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology. 2005;65:794–801.CrossRefPubMedGoogle Scholar
  13. 13.
    SPARCL Investigators. High-dose atorvastatin after stroke or transient ischemic attack. N Engl J Med. 2006;355:549–59.CrossRefGoogle Scholar
  14. 14.
    Amarenco P, Benavente O, Goldstein LB, et al. Results of the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial by stroke subtypes. Stroke. 2009;40:1405–9.CrossRefPubMedGoogle Scholar
  15. 15.
    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;39:3297–302.CrossRefPubMedGoogle Scholar
  16. 16.
    Merwick Á, Albers GW, Arsava EM, et al. Reduction in early stroke risk in carotid stenosis with transient ischemic attack associated with statin treatment. Stroke. 2013;44:2814–20.CrossRefPubMedGoogle Scholar
  17. 17.
    Amarenco P, Labreuche J, Lavallée P, Touboul P-J. Statins in stroke prevention and carotid atherosclerosis: systematic review and up-to-date meta-analysis. Stroke. 2004;35(12):2902–9.CrossRefPubMedGoogle Scholar
  18. 18.
    Tsivgoulis G, Katsanos AH, Sharma VK, et al. Statin pretreatment is associated with better outcomes in large artery atherosclerotic stroke. Neurology. 2016;86:1103–11.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Groschel K, Ernemann U, Schulz JB, et al. Statin therapy at carotid angioplasty and stent placement: effect on procedure-related stroke, myocardial infarction, and death. Radiology. 2006;240:145.CrossRefPubMedGoogle Scholar
  20. 20.
    Takayama K, Taki W, Toma N, et al. Effect of pitavastatin on preventing ischemic complications with carotid artery stenting: a multicenter prospective study—EPOCH-CAS study. Cardiovasc Intervent Radiol. 2014;37:1436–43.CrossRefPubMedGoogle Scholar
  21. 21.
    De Carlo M, Cortese B, Pennesi M, et al. Design of the rosuvastatin pretreatment to reduce embolization during Carotid Artery Stenting trial. J Cardiovasc Med (Hagerstown). 2014;15:595–600.CrossRefGoogle Scholar
  22. 22.
    MacMahon S, Sharpe N, Gamble G, et al. Effects of lowering average or below-average cholesterol levels on the progression of carotid atherosclerosis. Results of the LIPID atherosclerosis substudy. Circulation. 1998;97:1784–90.CrossRefPubMedGoogle Scholar
  23. 23.
    Okumura K, Tsukamoto H, Tsuboi H, et al. High HDL cholesterol level after treatment with pitavastatin is an important factor for regression in carotid intima-media thickness. Heart Vessel. 2015;30:154–61.CrossRefGoogle Scholar
  24. 24.
    Shahidi S, Owen-Falkenberg A, Hjerpsted U, et al. Urgent best medical therapy may obviate the need for urgent surgery in patients with symptomatic carotid stenosis. Stroke. 2013;44:2220–5.CrossRefPubMedGoogle Scholar
  25. 25.
    Chaturvedi S, Turan TN, Lynn MJ, et al. Do patient characteristics explain the differences in outcome between medically treated patients in SAMMPRIS and WASID? Stroke. 2015;46:2562–7.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Ibrahimi P, Jashari F, Bajraktari G, et al. Ultrasound assessment of carotid plaque echogenicity response to statin therapy: a systematic review and meta-analysis. Int J Mol Sci. 2015;16:10734–47.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Halliday A, Harrison M, Hayter E, et al. 10-year stroke prevention after successful carotid endarterectomy for asymptomatic stenosis (ACST-1): a multicentre randomised trial. Lancet. 2010;376:1074–84.CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Yan B, Peng L, Han D, et al. Blood pressure reverse-dipping is associated with early formation of carotid plaque in senior hypertensive patients. Medicine (Baltimore). 2015;94:e604.CrossRefGoogle Scholar
  29. 29.
    Markus HS, King A, Shipley M, et al. Asymptomatic embolisation for prediction of stroke in the Asymptomatic Carotid Emboli Study (ACES): a prospective observational study. Lancet Neurol. 2010;9:663–71.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Rothwell PM, Howard SC, Spence JD. Relationship between blood pressure and stroke risk in patients with symptomatic carotid occlusive disease. Stroke. 2003;34:2583–90.CrossRefPubMedGoogle Scholar
  31. 31.
    Inzitari D, Eliasziw M, Gates P, et al. The causes and risk of stroke in patients with asymptomatic internal-carotid-artery stenosis. N Engl J Med. 2000;342:1693–701.CrossRefPubMedGoogle Scholar
  32. 32.
    Chimowitz MI, Lynn MJ, Derdeyn CP, et al. Stenting versus aggressive medical therapy for intracranial arterial stenosis. N Engl J Med. 2011;365:993–1003.CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Zaidat OO, Fitzsimmons B, Woodward B, et al. Effect of a balloon-expandable intracranial stent vs medical therapy on risk of stroke in patients with symptomatic intracranial stenosis: the VISSIT randomized clinical trial. JAMA. 2015;313:1240–8.CrossRefPubMedGoogle Scholar
  34. 34.
    Marquardt L, Geraghty OC, Mehta Z, Rothwell PM. Low risk of ipsilateral stroke in patients with asymptomatic carotid stenosis on best medical treatment: a prospective, population-based study. Stroke. 2010;41:e11–7.CrossRefPubMedGoogle Scholar
  35. 35.
    den Hartog AG, Achterberg S, Moll FL, et al. Asymptomatic carotid artery stenosis and the risk of ischemic stroke according to subtype in patients with clinical manifest arterial disease. Stroke. 2013;44:1002–7.CrossRefGoogle Scholar
  36. 36.
    Spence JD, Coates V, Li H, et al. Effects of intensive medical therapy on microemboli and cardiovascular risk in asymptomatic carotid stenosis. Arch Neurol. 2010;67:180–6.CrossRefPubMedGoogle Scholar
  37. 37.
    Chaturvedi S, Chimowitz M, Brown RD, et al. The urgent need for contemporary clinical trials in patients with asymptomatic carotid stenosis. Neurology. 2016;87:2271.CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    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.CrossRefPubMedGoogle Scholar
  39. 39.
    Sabatine MS, Giugliano RP, Keech AC, et al. Evolocumab and clinical outcomes in patients with cardiovascular disease. N Engl J Med. 2017;376:1713–22.CrossRefPubMedGoogle Scholar

Copyright information

© The Author(s) 2018

Authors and Affiliations

  • Moayd M. Alkhalifah
    • 1
  • Paul M. Gadient
    • 1
  • Seemant Chaturvedi
    • 2
  1. 1.Vascular NeurologyUniversity of Miami Miller School of MedicineMiamiUSA
  2. 2.Vice-Chair for VA ProgramsUniversity of Miami Miller School of MedicineMiamiUSA

Personalised recommendations