Skip to main content

Advertisement

SpringerLink
Log in

Antithrombotic treatment of asymptomatic carotid atherosclerosis: a medical dilemma

  • IM - REVIEW
  • Published:
Internal and Emergency Medicine Aims and scope Submit manuscript

Abstract

Carotid artery atherosclerosis (CAAS) is a common finding in asymptomatic subjects evaluated for cardiovascular (CV)-risk stratification. Besides the careful control of CV-risk factors, antithrombotic agents, and in particular aspirin, may be considered for primary prevention in patients at CV-risk. However, there is strong controversy on the use of aspirin in primary prevention. Even if several studies confirmed the association between CAAS and CV-events, CAAS is not universally recognized as an independent risk factor and the choice to use aspirin as primary prevention in these patients remains a medical dilemma. Here we review the available evidence on the prognostic value of asymptomatic CAAS for major CV-events and on the utility of antithrombotic agents in this population. We conclude that the detection of asymptomatic CAAS can not be considered as a direct indication to carry out primary prophylaxis with antithrombotic drugs, and the choice to use aspirin should be made only after the careful estimate of the individual’s CV-and hemorrhagic risk.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Arnett DK, Blumenthal RS, Albert MA et al (2019) ACC/AHA guideline on the primary prevention of cardiovascular disease: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on clinical practice guidelines. J Am Coll Cardiol 74(10):1376–1414

    Article  Google Scholar 

  2. Antithrombotic Trialists' (ATT) Collaboration, Baigent C, Blackwell L, Collins R et al (2009) Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials. Lancet 373(9678):1849–1860. https://doi.org/10.1016/S0140-6736(09)60503-1

    Article  CAS  Google Scholar 

  3. Mahmoud AN, Gad MM, Elgendy AY et al (2019) Efficacy and safety of aspirin for primary prevention of cardiovascular events: a meta-analysis and trial sequential analysis of randomized controlled trials. Eur Heart J 40(7):607–617. https://doi.org/10.1093/eurheartj/ehy813

    Article  CAS  PubMed  Google Scholar 

  4. Halvorsen S, Andreotti F, ten Berg JM, Cattaneo M, Coccheri S, Marchioli R, Morais J, Verheugt FW, De Caterina R (2014) Aspirin therapy in primary cardiovascular disease prevention: a position paper of the European Society of Cardiology working group on thrombosis. J Am Coll Cardiol 64(3):319–327

    Article  CAS  Google Scholar 

  5. Volpe M, Abrignani MG, Borghi C, Coccheri S, Gresele P, Patti G, Trimarco B, De Caterina R (2014) Italian intersocietary consensus document on aspirin therapy in primary cardiovascular prevention. G Ital Cardiol (Rome) 15(78):442–451. https://doi.org/10.1714/1596.17424

    Article  Google Scholar 

  6. Gaziano JM, Brotons C, Coppolecchia R, Cricelli C, Darius H, Gorelick PB, Howard G, Pearson TA, Rothwell PM, Ruilope LM, Tendera M, Tognoni G, ARRIVE Executive Committee (2018) Use of aspirin to reduce risk of initial vascular events in patients at moderate risk of cardiovascular disease (ARRIVE): a randomised, double-blind, placebo-controlled trial. Lancet 392(10152):1036–1046. https://doi.org/10.1016/S0140-6736(18)31924-X

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. ASCEND Study Collaborative Group, Bowman L, Mafham M, Wallendszus K, Stevens W, Buck G, Barton J, Murphy K, Aung T, Haynes R, Cox J, Murawska A, Young A, Lay M, Chen F, Sammons E, Waters E, Adler A, Bodansky J, Farmer A, McPherson R, Neil A, Simpson D, Peto R, Baigent C, Collins R, Parish S, Armitage J (2018) Effects of aspirin for primary prevention in persons with diabetes mellitus. N Engl J Med 379(16):1529–1539. https://doi.org/10.1056/NEJMoa1804988

    Article  Google Scholar 

  8. McNeil JJ, Nelson MR, Woods RL, Lockery JE, Wolfe R, Reid CM, Kirpach B, Shah RC, Ives DG, Storey E, Ryan J, Tonkin AM, Newman AB, Williamson JD, Margolis KL, Ernst ME, Abhayaratna WP, Stocks N, Fitzgerald SM, Orchard SG, Trevaks RE, Beilin LJ, Donnan GA, Gibbs P, Johnston CI, Radziszewska B, Grimm R, Murray AM, ASPREE Investigator Group (2018) Effect of aspirin on all-cause mortality in the healthy elderly. N Engl J Med 379(16):1519–1528. https://doi.org/10.1056/NEJMoa1803955

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Zheng SL, Roddick AJ (2019) Association of aspirin use for primary prevention with cardiovascular events and bleeding events: a systematic review and meta-analysis. JAMA 321(3):277–287. https://doi.org/10.1001/jama.2018.20578

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Greenland P, Alpert JS, Beller GA, Benjamin EJ, Budoff MJ, Fayad ZA, Foster E, Hlatky MA, Hodgson JM, Kushner FG, Lauer MS, Shaw LJ, Smith SC Jr, Taylor AJ, Weintraub WS, Wenger NK, Jacobs AK, American College of Cardiology Foundation, American Heart Association Task Force on Practice Guidelines (2010) 2010 ACCF/AHA guideline for assessment of cardiovascular risk in asymptomatic adults: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation 122(25):e584–636. https://doi.org/10.1161/CIR.0b013e3182051b4c

    Article  PubMed  Google Scholar 

  11. Brott TG, Halperin JL, Abbara S, Bacharach JM, Barr JD, Bush RL, Cates CU, Creager MA, Fowler SB, Friday G, Hertzberg VS, McIff EB, Moore WS, Panagos PD, Riles TS, Rosenwasser RH, Taylor AJ (2011) 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. A report of the; American College of Cardiology; American Stroke Association; American Association of Neurological Surgeons; American College of Radiology; American American College of Radiology; Society of NeuroInterventional Surgery; Society for Vascular Medicine; Society for Vascular Surgery. 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 124(4):e54–130. https:doi.org/10.1161/CIR.0b013e31820d8c98

  12. Piepoli MF, Hoes AW, Agewall S et al; ESC Scientific Document Group (2016) 2016 European Guidelines on cardiovascular disease prevention in clinical practice: The Sixth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of 10 societies and by invited experts)Developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACPR). Eur Heart J 37(29):2315–2381. https://doi.org/10.1093/eurheartj/ehw106

  13. Stein JH, Korcarz CE, Hurst RT, Lonn E, Kendall CB, Mohler ER, Najjar SS, Rembold CM, Post WS (2008) Use of carotid ultrasound to identify subclinical vascular disease and evaluate cardiovascular disease risk: a consensus statement from the American Society of Echocardiography Carotid Intima-Media Thickness Task Force. Endorsed by the Society for Vascular Medicine. American Society of Echocardiography Carotid Intima-Media Thickness Task Force. J Am Soc Echocardiogr 21(2):93–111. https://doi.org/10.1016/j.echo.2007.11.011

  14. Touboul PJ, Hennerici MG, Meairs S, Adams H, Amarenco P, Bornstein N, Csiba L, Desvarieux M, Ebrahim S, Hernandez Hernandez R, Jaff M, Kownator S, Naqvi T, Prati P, Rundek T, Sitzer M, Schminke U, Tardif JC, Taylor A, Vicaut E, Woo KS (2011) Mannheim carotid intima-media thickness and plaque consensus (2004–2006-2011) (2012) An update on behalf of the advisory board of the 3rd, 4th and 5th watching the risk symposia, at the 13th, 15th and 20th European Stroke Conferences, Mannheim, Germany, 2004, Brussels, Belgium, 2006, and Hamburg, Germany. Cerebrovasc Dis 34(4):290–296. https://doi.org/10.1159/000343145

    Article  Google Scholar 

  15. Sprynger M, Rigo F, Moonen M, Aboyans V, Edvardsen T, de Alcantara ML, Brodmann M, Naka KK, Kownator S, Simova I, Vlachopoulos C, Wautrecht JC, Lancellotti P, EACVI Scientific Documents Committee (2018) Focus on echovascular imaging assessment of arterial disease: complement to the ESC guidelines (PARTIM 1) in collaboration with the Working Group on Aorta and Peripheral Vascular Diseases. Eur Heart J Cardiovasc Imaging 19(11):1195–1221. https://doi.org/10.1093/ehjci/jey103

    Article  PubMed  Google Scholar 

  16. Handa N, Matsumoto M, Maeda H et al (1990) Ultrasonic evaluation of early carotid atherosclerosis. Stroke 21:1567–1572. https://doi.org/10.1161/01.str.21.11.1567

    Article  CAS  PubMed  Google Scholar 

  17. Calogero E, Fabiani I, Pugliese NR, Santini V, Ghiadoni L, Di Stefano R, Galetta F, Sartucci F, Penno G, Berchiolli R, Ferrari M, Cioni D, Napoli V, De Caterina R, Di Bello V, Caramella D (2018) Three-dimensional echographic evaluation of carotid artery disease. J Cardiovasc Echogr 28(4):218–227. https://doi.org/10.4103/jcecho.jcecho_57_18

    Article  PubMed  PubMed Central  Google Scholar 

  18. Prati P, Tosetto A, Casaroli M, Bignamini A, Canciani L, Bornstein N, Prati G, Touboul PJ (2011) Carotid plaque morphology improves stroke risk prediction: usefulness of a new ultrasonographic score. Cerebrovasc Dis 31(3):300–304. https://doi.org/10.1159/000320852

    Article  CAS  PubMed  Google Scholar 

  19. Sulženko J, Paluszek P, Machnik R et al (2019) Prevalence and predictors of coronary artery disease in patients undergoing carotid artery stenting. Coron Artery Dis. 30(3):204–210. https://doi.org/10.1097/MCA.0000000000000695

    Article  PubMed  Google Scholar 

  20. Hertzer NR, Young JR, Beven EG et al (1985) Coronary angiography in 506 patients with extracranial cerebrovascular disease. Arch Intern Med 145:849–852

    Article  CAS  Google Scholar 

  21. Ikeda N, Kogame N, Iijima R, Nakamura M, Sugi K (2012) Carotid artery intima-media thickness and plaque score can predict the SYNTAX score. Eur Heart J 33(1):113–119. https://doi.org/10.1093/eurheartj/ehr399

    Article  PubMed  Google Scholar 

  22. Amato M, Montorsi P, Ravani A et al (2007) Carotid intima-media thickness by B-mode ultrasound as surrogate of coronary atherosclerosis: correlation with quantitative coronary angiography and coronary intravascular ultrasound findings. Eur Heart J 28(17):2094–2101. https://doi.org/10.1093/eurheartj/ehm244

    Article  PubMed  Google Scholar 

  23. Raso FM, Van Popele NM, Schalekamp MA, Van Der Cammen TJ (2002) Intima-media thickness of the common carotid arteries is related to coronary atherosclerosis and left ventricular hypertrophy in older adults. Angiology 53:569–574. https://doi.org/10.1177/000331970205300511

    Article  Google Scholar 

  24. Crouse JR 3rd, Tang R, Espeland MA et al (2002) Associations of extracranial carotid atherosclerosis progression with coronary status and risk factors in patients with and without coronary artery disease. Circulation 106:2061–2066. https://doi.org/10.1161/01.cir.0000033833.54884.34

    Article  CAS  PubMed  Google Scholar 

  25. Long TH, Criqui MH, Vasilevskis EE, Denenberg JO, Klauber MR, Fronek A (1999) The correlation between the severity of peripheral arterial disease and carotid occlusive disease. Vasc Med 4(3):135–142. https://doi.org/10.1177/1358836X9900400303

    Article  CAS  PubMed  Google Scholar 

  26. Poredos P, Golob M, Jensterle M (2003) Interrelationship between peripheral arterial occlusive disease, carotid atherosclerosis and flow mediated dilation of the brachial artery. Int Angiol 22(1):83–87

    CAS  PubMed  Google Scholar 

  27. Bez LG, Navarro TP (2014) Study of carotid disease in patients with peripheral artery disease. Rev Col Bras Cir 41(5):311–318. https://doi.org/10.1590/0100-69912014005003

    Article  PubMed  Google Scholar 

  28. Simons PCG, Algra A, Eikelboom BC, Grobbee DE, van der Graaf Y, For the SMART study group (1999) Carotid artery stenosis in patients with peripheral arterial disease: the SMART. J Vasc Surg 30:519–525. https://doi.org/10.1016/s0741-5214(99)70079-0

    Article  CAS  PubMed  Google Scholar 

  29. Pan Z, Wang R, Li L, Zhang H (2019) Correlation between significant asymptomatic carotid artery stenosis and severity of peripheral arterial occlusive disease in the lower limb: a retrospective study on 200 patients. BMC Neurol 19(1):259–263. https://doi.org/10.1186/s12883-019-1485-1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Jung HJ, Lee SS, Kim HY, Park BS, Kim DI, Nam KJ, Roh JE, Choo KS (2019) Association between carotid artery stenosis and peripheral artery disease: evaluation by screening carotid ultrasonography (cross-sectional study). Medicine (Baltimore) 98(6):e14163. https://doi.org/10.1097/MD.0000000000014163

    Article  Google Scholar 

  31. Arya S, Khakharia A, Binney ZO, DeMartino RR, Brewster LP, Goodney PP, Wilson PWF (2018) Association of statin dose with amputation and survival in patients with peripheral artery disease. Circulation 137(14):1435–1446. https://doi.org/10.1161/CIRCULATIONAHA.117.032361

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Nakamura S, Iihara K, Matayoshi T, Yasuda H, Yoshihara F, Kamide K, Horio T, Miyamoto Kawano S (2007) The incidence and risk factors of renal artery stenosis in patients with severe carotid artery stenosis. Hypertens Res 30(9):839–844. https://doi.org/10.1291/hypres.30.839

    Article  CAS  PubMed  Google Scholar 

  33. Novo G, Guarneri FP, Ferro G, Russo R, Fattouch K, Novo S (2012) Association between asymptomatic carotid atherosclerosis and degenerative aortic stenosis. Atherosclerosis 223(2):519–522. https://doi.org/10.1016/j.atherosclerosis.2012.06.011

    Article  CAS  PubMed  Google Scholar 

  34. Rothwell PM, Gibson R, Warlow CP (2000) Interrelation between plaque surface morphology and degree of stenosis on carotid angiograms and the risk of ischemic stroke in patients with symptomatic carotid stenosis. On behalf of the European Carotid Surgery Trialists' Collaborative Group. Stroke 31(3):615–21. https://doi.org/10.1161/01.str.31.3.615

  35. Nicolaides AN, Kakkos SK, Kyriacou E, Griffin M, Sabetai M, Thomas DJ, Tegos T, Geroulakos G, Labropoulos N, Doré CJ, Morris TP, Naylor R, Abbott AL; Asymptomatic Carotid Stenosis and Risk of Stroke (ACSRS) Study Group (2010) Asymptomatic internal carotid artery stenosis and cerebrovascular risk stratification. J Vasc Surg 52(6):1486–1496.e1–5. https://doi.org/10.1016/j.jvs.2010.07.021

  36. Finn AV, Nakano M, Narula J, Kolodgie FD, Virmani R (2010) Concept of vulnerable/unstable plaque. Arterioscler Thromb Vasc Biol 30(7):1282–1292. https://doi.org/10.1161/ATVBAHA.108.179739

    Article  CAS  PubMed  Google Scholar 

  37. Liem MI, Kennedy F, Bonati LH et al (2017) Investigations of carotid stenosis to identify vulnerable atherosclerotic plaque and determine individual stroke risk. Circ J 81(9):1246–1253. https://doi.org/10.1253/circj.CJ-16-1284

    Article  PubMed  Google Scholar 

  38. Gupta A, Kesavabhotla K, Baradaran H, Kamel H, Pandya A, Giambrone AE, Wright D, Pain KJ, Mtui EE, Suri JS, Sanelli PC, Mushlin AI (2015) Plaque echolucency and stroke risk in asymptomatic carotid stenosis: a systematic review and meta-analysis. Stroke 46(1):91–97. https://doi.org/10.1161/STROKEAHA.114.006091

    Article  PubMed  Google Scholar 

  39. Jashari F, Ibrahimi P, Bajraktari G, Grönlund C, Wester P, Henein MY (2016) Carotid plaque echogenicity predicts cerebrovascular symptoms: a systematic review and meta-analysis. Eur J Neurol 23(7):1241–1247. https://doi.org/10.1111/ene.13017

    Article  CAS  PubMed  Google Scholar 

  40. Makowski MR (2013) MR imaging of the arterial vessel wall: molecular imaging. Radiology 269(1):34–51. https://doi.org/10.1148/radiol.13102336

    Article  PubMed  Google Scholar 

  41. Saam T, Hetterich H, Hoffmann V et al (2013) Meta-analysis and systematic review of the predictive value of carotid plaque hemorrhage on cerebrovascular events by magnetic resonance imaging. J Am Coll Cardiol 62(12):1081–1091. https://doi.org/10.1016/j.jacc.2013.06.015

    Article  PubMed  Google Scholar 

  42. Wintermark M, Arora S, Tong E (2008) Carotid plaque computed tomography imaging in stroke and nonstroke patients. Ann Neurol 64(2):149–157. https://doi.org/10.1002/ana.21424

    Article  PubMed  PubMed Central  Google Scholar 

  43. Magge R, Lau BC, Soares BP, Fischette S, Arora S, Tong E, Cheng S, Wintermark M (2013) Clinical risk factors and CT imaging features of carotid atherosclerotic plaques as predictors of new incident carotid ischemic stroke: a retrospective cohort study. Am J Neuroradiol 34(2):402–409. https://doi.org/10.3174/ajnr.A3228

    Article  CAS  PubMed  Google Scholar 

  44. Kooi ME, Cappendijk VC, Cleutjens KBJM, Kessels AGH, Kitslaar PJE, Borgers M et al (2003) Accumulation of ultrasmall superparamagnetic particles of iron oxide in human atherosclerotic plaques can be detected by in vivo magnetic resonance imaging. Circulation 107(19):2453–2462. https://doi.org/10.1161/01.CIR.0000068315.98705.CC

    Article  CAS  PubMed  Google Scholar 

  45. Chan JM, Monaco C, Wylezinska-Arridge M, Tremoleda JL, Gibbs RG (2014) Imaging of the vulnerable carotid plaque: biological targeting of inflammation in atherosclerosis using iron oxide particles and MRI. Eur J Vasc Endovasc Surg 47(5):462–469. https://doi.org/10.1016/j.ejvs.2014.01.017

    Article  CAS  PubMed  Google Scholar 

  46. Busti C, Falcinelli E, Momi S, Gresele P (2010) Matrix metalloproteinases and peripheral arterial disease. Intern Emerg Med 5(1):13–25. https://doi.org/10.1007/s11739-009-0283-y

    Article  PubMed  Google Scholar 

  47. Gresele P, Falcinelli E, Sebastiano M, Momi S (2017) Matrix metalloproteinases and platelet function. Prog Mol Biol Transl Sci 147:133–165. https://doi.org/10.1016/bs.pmbts.2017.01.002

    Article  CAS  PubMed  Google Scholar 

  48. Lancelot E, Amirbekian V, Brigger I, Raynaud JS, Ballet S, David C, Rousseaux O, Le Greneur S, Port M, Lijnen HR, Bruneval P, Michel JB, Ouimet T, Roques B, Amirbekian S, Hyafil F, Vucic E, Aguinaldo JG, Corot C, Fayad ZA (2008) Evaluation of matrix metalloproteinases in atherosclerosis using a novel noninvasive imaging approach. Arterioscler Thromb Vasc Biol 28(3):425–432. https://doi.org/10.1161/ATVBAHA.107.149666

    Article  CAS  PubMed  Google Scholar 

  49. Marturano A, Hendrickx MLV, Falcinelli E, Sebastiano M, Guglielmini G, Hassanzadeh-Ghassabeh G, Muyldermans S, Declerck PJ, Gresele P (2020) Development of anti-matrix metalloproteinase-2 (MMP-2) nanobodies as potential therapeutic and diagnostic tools. Nanomedicine 24:102103. https://doi.org/10.1016/j.nano.2019.102103

    Article  CAS  PubMed  Google Scholar 

  50. Casscells W, Hathorn B, David M, Krabach T, Vaughn WK, McAllister HA, Bearman G, Willerson JT (1996) Thermal detection of cellular infiltrates in living atherosclerotic plaques: possible implications for plaque rupture and thrombosis. Lancet 347(9013):1447–1451. https://doi.org/10.1016/s0140-6736(96)91684-0

    Article  CAS  PubMed  Google Scholar 

  51. Kruizinga P, van der Steen AFW, de Jong N, Springeling G, Robertus JL, van der Lugt A et al (2014) Photoacoustic imaging of carotid artery atherosclerosis. J Biomed Opt 19(11):110504. https://doi.org/10.1117/1.JBO.19.11.110504

    Article  PubMed  Google Scholar 

  52. Carmo GA, Calderaro D, Gualandro DM, Casella IB, Yu PC, Marques AC, Caramelli B (2014) Carotid stenosis management: a review for the internist. Intern Emerg Med 9(2):133–142. https://doi.org/10.1007/s11739-013-1005-z

    Article  PubMed  Google Scholar 

  53. Lorenz MW, Markus HS, Bots ML et al (2007) Prediction of clinical cardiovascular events with carotid intima-media thickness: a systematic review and meta-analysis. Circulation 115(4):459–467. https://doi.org/10.1161/CIRCULATIONAHA.106.628875

    Article  PubMed  Google Scholar 

  54. Polak JF, Pencina MJ, Pencina KM et al (2011) Carotid-wall intima-media thickness and cardiovascular events. N Engl J Med 365(3):213–221. https://doi.org/10.1056/NEJMoa1012592

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Van der Meer IM, Bots ML, Hofman A, del Sol AI, van der Kuip DA, Witteman JC (2004) Predictive value of noninvasive measures of atherosclerosis for incident myocardial infarction: the Rotterdam Study. Circulation 109(9):1089–1094. https://doi.org/10.1161/01.CIR.0000120708.59903.1B

    Article  PubMed  Google Scholar 

  56. Belcaro G, Nicolaides AN, Ramaswami G, Cesarone MR, DeSanctis M, Incandela L et al (2001) Carotid and femoral ultrasound morphology screening and cardiovascular events in low risk subjects: a 10-year follow-up study (the CAFES-CAVE study). Atherosclerosis 156(2):379–387. https://doi.org/10.1016/s0021-9150(00)00665-1

    Article  CAS  PubMed  Google Scholar 

  57. Nambi V, Chambless L, Folsom AR, He M, Hu Y, Mosley T, Volcik K, Boerwinkle E, Ballantyne CM (2010) Carotid intima-media thickness and presence or absence of plaque improves prediction of coronary heart disease risk: the ARIC (Atherosclerosis Risk In Communities) study. J Am Coll Cardiol 55(15):1600–1607. https://doi.org/10.1016/j.jacc.2009.11.075

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Giannopoulos A, Kakkos S, Abbott A et al (2015) Long-term mortality in patients with asymptomatic carotid stenosis: implications for statin therapy. Eur J Vasc Endovasc Surg 50(5):573–582. https://doi.org/10.1016/j.ejvs.2015.06.115

    Article  CAS  PubMed  Google Scholar 

  59. Johnsen SH, Mathiesen EB, Joakimsen O, Stensland E, Wilsgaard T, Løchen ML, Njølstad I, Arnesen E (2007) Carotid atherosclerosis is a stronger predictor of myocardial infarction in women than in men: a 6-year follow-up study of 6226 persons: the Tromsø Study. Stroke 38(11):2873–2880. https://doi.org/10.1161/STROKEAHA.107.487264

    Article  PubMed  Google Scholar 

  60. Mathiesen EB, Johnsen SH, Wilsgaard T, Bønaa KH, Løchen ML, Njølstad I (2011) Carotid plaque area and intima-media thickness in prediction of first-ever ischemic stroke: a 10-year follow-up of 6584 men and women: the Tromsø Study. Stroke 42(4):972–978. https://doi.org/10.1161/STROKEAHA.110.589754

    Article  PubMed  Google Scholar 

  61. Störk S, van den Beld AW, von Schacky C et al (2004) Carotid artery plaque burden, stiffness, and mortality risk in elderly men: a prospective, population-based cohort study. Circulation 110(3):344–348. https://doi.org/10.1161/01.CIR.0000134966.10793.C9

    Article  PubMed  Google Scholar 

  62. Nonin S, Iwata S, Sugioka K, Fujita S, Norioka N, Ito A, Nakagawa M, Yoshiyama M (2017) Plaque surface irregularity and calcification length within carotid plaque predict secondary events in patients with coronary artery disease. Atherosclerosis 256:29–34. https://doi.org/10.1016/j.atherosclerosis.2016.11.008

    Article  CAS  PubMed  Google Scholar 

  63. Sillesen H, Muntendam P, Adourian A, Entrekin R, Garcia M, Falk E et al (2012) Carotid plaque burden as a measure of subclinical atherosclerosis: comparison with other tests for subclinical arterial disease in the High Risk Plaque BioImage study. JACC Cardiovasc Imaging 5:681–689. https://doi.org/10.1016/j.jcmg.2012.03.013

    Article  PubMed  Google Scholar 

  64. Baber U, Mehran R, Sartori S, Schoos MM, Sillesen H, Muntendam P, Garcia MJ, Gregson J, Pocock S, Falk E, Fuster V (2015) Prevalence, impact, and predictive value of detecting subclinical coronary and carotid atherosclerosis in asymptomatic adults: the BioImage study. J Am Coll Cardiol 65(11):1065–1074. https://doi.org/10.1016/j.jacc.2015.01.017

    Article  PubMed  Google Scholar 

  65. Wannarong T, Parraga G, Buchanan D, Fenster A, House AA, Hackam DG, Spence JD (2013) Progression of carotid plaque volume predicts cardiovascular events. Stroke 44(7):1859–1865. https://doi.org/10.1161/STROKEAHA.113.001461

    Article  PubMed  Google Scholar 

  66. Amarenco P, Bogousslavsky J, Callahan A 3rd, Goldstein LB, Hennerici M, Rudolph AE, Sillesen H, Simunovic L, Szarek M, Welch KM, Zivin JA, Sroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) Investigators (2006) High-dose atorvastatin after stroke or transient ischemic attack. N Engl J Med 355(6):549–559. https://doi.org/10.1056/NEJMoa061894

    Article  CAS  PubMed  Google Scholar 

  67. Rothwell PM, Howard SC, Spence JD, Collaboration CET (2003) Relationship between blood pressure and stroke risk in patients with symptomatic carotid occlusive disease. Stroke 34(11):2583–2590. https://doi.org/10.1161/01.STR.0000094424.38761.56

    Article  CAS  PubMed  Google Scholar 

  68. Vandvik PO, Lincoff AM, Gore JM et al (2012) Primary and secondary prevention of cardiovascular disease: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest 141(2 Suppl):e637S–e668S. https://doi.org/10.1378/chest.11-2306

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Côté R, Battista RN, Abrahamowicz M et al. (1995) Lack of effect of aspirin in asymptomatic patients with carotid bruits and substantial carotid narrowing. The Asymptomatic Cervical Bruit Study Group. Ann Intern Med 123(9):649–55

  70. King A, Shipley M, Markus H, Investigators ACES (2013) The effect of medical treatments on stroke risk in asymptomatic carotid stenosis. Stroke 44(2):542–546. https://doi.org/10.1161/STROKEAHA.112.673608

    Article  CAS  PubMed  Google Scholar 

  71. Bhatt DL, Fox KA, Hacke W, Berger PB, Black HR, Boden WE, Cacoub P, Cohen EA, Creager MA, Easton JD, Flather MD, Haffner SM, Hamm CW, Hankey GJ, Johnston SC, Mak KH, Mas JL, Montalescot G, Pearson TA, Steg PG, Steinhubl SR, Weber MA, Brennan DM, Fabry-Ribaudo L, Booth J, Topol EJ, CHARISMA Investigators (2006) Clopidogrel and aspirin versus aspirin alone for the prevention of atherothrombotic events. N Engl J Med 354(16):1706–1772. https://doi.org/10.1056/NEJMoa060989

    Article  CAS  PubMed  Google Scholar 

  72. Huang R, Mills K, Romero J et al (2019) Comparative effects of lipid lowering, hypoglycemic, antihypertensive and antiplatelet medications on carotid artery intima-media thickness progression: a network meta-analysis. Cardiovasc Diabetol 18(1):14. https://doi.org/10.1186/s12933-019-0817-1

    Article  PubMed  PubMed Central  Google Scholar 

  73. Willeit P, Tschiderer L, Allara E, Reuber K, Seekircher L, Gao L, Liao X, Lonn E, Gerstein HC, Yusuf S, Brouwers FPJ, Asselbergs FW, van Gilst W, Anderssen SA, Grobbee DE, Kastelein JJP, Visseren FLJ, Ntaios G, Hatzitolios AI, Savopoulos C, Nieuwkerk PT, Stroes E, Walters M, Higgins P, Dawson J, Gresele P, Guglielmini G, Migliacci R, Sato E, Amaha M, Nakamura T, Kapellas K, Jamieson LM, Skilton M, Blumenthal JA, Hinderliter A, Sherwood A, Smith PJ, van Agtmael MA, Reiss P, van Vonderen MGA, Kiechl S, Klingenschmid G, Sitzer M, Stehouwer CDA, Uthoff H, Zou Z-Y, Cunha AR, Fritsch Neves M, Witham MD, Park HW, Lee M-S, Bae J-H, Bernal E, Wachtell K, Kjeldsen SE, Olsen MH, Helmond FA, Preiss D, Sattar N (2020) Carotid intima-media thickness progression as surrogate marker for cardiovascular risk: meta-analysis of 119 clinical trials involving 100,667 patients. Circulation. https://doi.org/10.1161/CIRCULATIONAHA.120.046361

    Article  PubMed  Google Scholar 

  74. Alonso-Coello P, Bellmunt S, McGorrian C, et al. (2012) Antithrombotic therapy in peripheral artery disease: antithrombotic therapy and prevention of thrombosis, 9th edn: American College of Chest. Physicians evidence-based clinical practice guidelines. Chest 141(2 Suppl):e669S–e690S. https://doi.org/10.1378/chest.11-2307

  75. Aboyans V, Ricco JB, Bartelink MEL et al (2018) 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 arteries. Endorsed 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 39(9):763–781. https://doi.org/10.1093/eurheartj/ehx095

  76. Eikelboom JW, Connolly SJ, Bosch J, Dagenais GR, Hart RG, Shestakovska O, Diaz R, Alings M, Lonn EM, Anand SS, Widimsky P, Hori M, Avezum A, Piegas LS, Branch KRH, Probstfield J, Bhatt DL, Zhu J, Liang Y, Maggioni AP, Lopez-Jaramillo P, O'Donnell M, Kakkar AK, Fox KAA, Parkhomenko AN, Ertl G, Störk S, Keltai M, Ryden L, Pogosova N, Dans AL, Lanas F, Commerford PJ, Torp-Pedersen C, Guzik TJ, Verhamme PB, Vinereanu D, Kim JH, Tonkin AM, Lewis BS, Felix C, Yusoff K, Steg PG, Metsarinne KP, Cook Bruns N, Misselwitz F, Chen E, Leong D, Yusuf S, COMPASS Investigators (2017) Rivaroxaban with or without aspirin in stable cardiovascular disease. N Engl J Med 377(14):1319–1330. https://doi.org/10.1056/NEJMoa1709118

    Article  CAS  PubMed  Google Scholar 

  77. Anand SS, Bosch J, Eikelboom JW et al (2018) Rivaroxaban with or without aspirin in patients with stable peripheral or carotid artery disease: an international, randomised, double-blind, placebo-controlled trial. Lancet 391(10117):219–229. https://doi.org/10.1016/S0140-6736(17)32409-1

    Article  CAS  PubMed  Google Scholar 

  78. CAPRIE Steering Committee (1996) A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). Lancet 348(9038):1329–1339. https://doi.org/10.1016/s0140-6736(96)09457-3

    Article  Google Scholar 

  79. Wang TH, Bhatt DL, Fox KA et al (2007) An analysis of mortality rates with dual-antiplatelet therapy in the primary prevention population of the CHARISMA trial. Eur Heart J 28(18):2200–2207. https://doi.org/10.1093/eurheartj/ehm274

    Article  PubMed  Google Scholar 

  80. Gresele P, Momi S, Falcinelli E (2011) Anti-platelet therapy: phosphodiesterase inhibitors. Br J Clin Pharmacol 72(4):634–646. https://doi.org/10.1111/j.1365-2125.2011.04034.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Lee WH, Chu CY, Hsu PC et al (2013) Cilostazol for primary prevention of stroke in peripheral artery disease: a population-based longitudinal study in Taiwan. Thromb Res 132(2):190–195. https://doi.org/10.1016/j.thromres.2013.01.036

    Article  CAS  PubMed  Google Scholar 

  82. Lip GY (2011) Implications of the CHA(2)DS(2)-VASc and HAS-BLED Scores for thromboprophylaxis in atrial fibrillation. Am J Med 124(2):111–114. https://doi.org/10.1016/j.amjmed.2010.05.007

    Article  PubMed  Google Scholar 

  83. Rosenberg DJ, Press A, Fishbein J et al (2016) External validation of the IMPROVE bleeding risk assessment model in medical patients. Thromb Haemost 116(3):530–536. https://doi.org/10.1160/TH16-01-0003

    Article  PubMed  Google Scholar 

  84. Nishimoto Y, Yamashita Y, Morimoto T et al (2020) Validation of the VTE-BLEED score's long-term performance for major bleeding in patients with venous thromboembolisms: From the COMMAND VTE registry. J Thromb Haemost 18(3):624–632. https://doi.org/10.1111/jth.14691

    Article  PubMed  Google Scholar 

  85. Costa F, van Klaveren D, James S et al (2017) Derivation and validation of the predicting bleeding complications in patients undergoing stent implantation and subsequent dual antiplatelet therapy (PRECISE-DAPT) score: a pooled analysis of individual-patient datasets from clinical trials. Lancet 389(10073):1025–1034. https://doi.org/10.1016/S0140-6736(17)30397-5

    Article  PubMed  Google Scholar 

  86. Lanas A, Polo-Tomás M, Casado-Arroyo R (2013) The aspirin cardiovascular/gastrointestinal risk calculator—a tool to aid clinicians in practice. Aliment Pharmacol Ther 37(7):738–748. https://doi.org/10.1111/apt.12240

    Article  CAS  PubMed  Google Scholar 

  87. Whitlock EP, Burda BU, Williams SB, Guirguis-Blake JM, Evans CV (2016) Bleeding risks with aspirin use for primary prevention in adults: a systematic review for the U.S. preventive services task force. Ann Intern Med 164(12):826–35. Ttps://doi.org/10.7326/M15-2112

  88. Näslund U, Ng N, Lundgren A, VIPVIZA trial group et al (2019) Visualization of asymptomatic atherosclerotic disease for optimum cardiovascular prevention (VIPVIZA): a pragmatic, open-label, randomised controlled trial. Lancet 393(10167):133–142. https://doi.org/10.1016/S0140-6736(18)32818-6

    Article  PubMed  Google Scholar 

  89. 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 (1991) Beneficial effect of carotid endarterectomy in symptomatic patients with high-grade carotid stenosis. N Engl J Med 325(7):445–453. https://doi.org/10.1056/NEJM199108153250701

    Article  Google Scholar 

  90. Zhang Q, Wang A, Zhang S, Li N, Chen S, Zhang Y, Zhou Y, Wu S, Zhao X (2017) Asymptomatic polyvascular disease and the risks of cardiovascular events and all-cause death. Atherosclerosis 262:1–7. https://doi.org/10.1016/j.atherosclerosis.2017.04.015

    Article  CAS  PubMed  Google Scholar 

  91. Manes C, Giacci L, Sciartilli A, D'Alleva A, De Caterina R (2006) Aspirin overprescription in primary cardiovascular prevention. Thromb Res 118(4):471–477. https://doi.org/10.1016/j.thromres.2005.09.013

    Article  CAS  PubMed  Google Scholar 

  92. VanWormer JJ, Miller AW, Rezkalla SH (2014) Aspirin overutilization for the primary prevention of cardiovascular disease. Clin Epidemiol 6:433–440. https://doi.org/10.2147/CLEP.S72032

    Article  PubMed  PubMed Central  Google Scholar 

  93. Gresele P (2013) Antiplatelet agents in clinical practice and their haemorrhagic risk. Blood Transfus 11(3):349–356. https://doi.org/10.2450/2013.0248-12

    Article  PubMed  PubMed Central  Google Scholar 

  94. Chiang KF, Shah SJ, Stafford RS (2019) A practical approach to low-dose aspirin for primary prevention. JAMA. https://doi.org/10.1001/jama.2019.8388

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

Secretarial assistance by Mrs. Silvia Spaccini is gratefully acknowledged. This work was supported in part by a grant to P.G from Fondazione Cassa di Risparmio di Perugia (Grant #8220, SIME 2018.0411).

Author information

Authors and Affiliations

  1. Section of Internal and Cardiovascular Medicine, Department of Medicine, University of Perugia, Strada Vicinale Via Delle Corse, S. Andrea della Fratte, 06132, Perugia, Italy

    Paolo Gresele & Francesco Paciullo

  2. Division of Internal Medicine, Ospedale Della Valdichiana “S. Margherita”, Cortona, Italy

    Rino Migliacci

Authors
  1. Paolo Gresele
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Francesco Paciullo
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Rino Migliacci
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Paolo Gresele.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Statement of human and animal rights

This article does not contain any studies with human participants or animals performed by any of the authors.

Informed consent

All participants provided informed consent prior to their participant.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Gresele, P., Paciullo, F. & Migliacci, R. Antithrombotic treatment of asymptomatic carotid atherosclerosis: a medical dilemma. Intern Emerg Med 15, 1169–1181 (2020). https://doi.org/10.1007/s11739-020-02347-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11739-020-02347-7

Keywords

Search

Navigation