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Journal of Thrombosis and Thrombolysis

, Volume 48, Issue 1, pp 68–76 | Cite as

Use of oral anticoagulant drugs is associated with carotid intraplaque hemorrhage in atherosclerosis patients: a meta-analysis

  • Xin Cao
  • Jun ZhangEmail author
  • Daoying GengEmail author
Article
  • 284 Downloads

Abstract

Patients with carotid atherosclerosis, especially the elderly population, take antithrombotic medicine regularly. However, no previous meta-analysis has focused on one of the possible side effects of such drugs, namely intraplaque hemorrhage (IPH). To determine whether antiplatelet drugs or anticoagulants are associated with an increased risk of carotid IPH. We searched Pubmed, Embase, Ovid MEDLINE, Cochrane Library for relevant studies that were published in English, from January 1st, 1989 to January 1st, 2019. We pooled the odds ratio (OR) with 95% confidence interval (CI) from individual studies and conducted quality assessment, heterogeneity, publication bias analysis and sensitivity analysis. A total of four cross-sectional studies, involving 2714 participants with carotid atherosclerotic plaques was included into this meta-analysis. We found a significant association between the use of anticoagulants and higher risk of carotid IPH (OR 1.95; 95% CI 1.16–3.30, P = 0.92; I2 = 0). No significant association was found between the use of antiplatelet drugs and increased risk of carotid IPH (OR 1.34; 95% CI 0.68–2.61, P = 0.03; I2 = 65%). Our meta-analysis reveals that it is the use of oral anticoagulants rather than antiplatelet drugs that may be associated with an increased risk of carotid IPH in atherosclerosis patients.

Keywords

Intraplaque hemorrhage Carotid atherosclerosis Antithrombotic Antiplatelet Anticoagulants 

Notes

Acknowledgements

All authors have full access to all data in the study. Daoying Geng and Jun Zhang take responsibility for the integrity of the data and the accuracy of data analysis. All Authors read and approved the final version of the manuscript.

Funding

The research was funded by the National Key Research and Development Program of China (Grant No. 2016YFA0203700), the Shanghai Municipal Commission of Health (No. 2017BR003), and Shanghai Municipal Commission of Science and Technology (No. 16QA1400900, No. 16410722800, No. 17411953700).

Compliance with ethical standards

Conflict of interest

All authors declare no conflicts of interest.

Supplementary material

11239_2019_1865_MOESM1_ESM.txt (1 kb)
Supplementary material 1 (TXT 1 kb)

References

  1. 1.
    Cai JM, Hatsukami TS, Ferguson MS, Small R, Polissar NL, Yuan C (2002) Classification of human carotid atherosclerotic lesions with in vivo multicontrast magnetic resonance imaging. Circulation 106(11):1368–1373CrossRefGoogle Scholar
  2. 2.
    Stary HC, Chandler AB, Dinsmore RE, Fuster V, Glagov S, Insull W Jr, Rosenfeld ME, Schwartz CJ, Wagner WD, Wissler RW (1995) A definition of advanced types of atherosclerotic lesions and a histological classification of atherosclerosis. A report from the Committee on Vascular Lesions of the Council on Arteriosclerosis, American Heart Association. Circulation 92(5):1355–1374CrossRefGoogle Scholar
  3. 3.
    Stary HC, Chandler AB, Glagov S, Guyton JR, Insull W Jr, Rosenfeld ME, Schaffer SA, Schwartz CJ, Wagner WD, Wissler RW (1994) A definition of initial, fatty streak, and intermediate lesions of atherosclerosis. Arterioscler Thromb 14(5):840–856CrossRefGoogle Scholar
  4. 4.
    Kolodgie FD, Gold HK, Burke AP, Fowler DR, Kruth HS, Weber DK, Farb A, Guerrero LJ, Hayase M, Kutys R, Narula J, Finn AV, Virmani R (2003) Intraplaque hemorrhage and progression of coronary atheroma. N Engl J Med 349(24):2316–2325.  https://doi.org/10.1056/NEJMoa035655 CrossRefGoogle Scholar
  5. 5.
    Takaya N, Yuan C, Chu B, Saam T, Polissar NL, Jarvik GP, Isaac C, McDonough J, Natiello C, Small R, Ferguson MS, Hatsukami TS (2005) Presence of intraplaque hemorrhage stimulates progression of carotid atherosclerotic plaques: a high-resolution magnetic resonance imaging study. Circulation 111(21):2768–2775.  https://doi.org/10.1161/circulationaha.104.504167 CrossRefGoogle Scholar
  6. 6.
    Kockx MM, Cromheeke KM, Knaapen MW, Bosmans JM, De Meyer GR, Herman AG, Bult H (2003) Phagocytosis and macrophage activation associated with hemorrhagic microvessels in human atherosclerosis. Arterioscler Thromb Vasc Biol 23(3):440–446.  https://doi.org/10.1161/01.Atv.0000057807.28754.7f CrossRefGoogle Scholar
  7. 7.
    Levy AP, Moreno PR (2006) Intraplaque hemorrhage. Curr Mol Med 6(5):479–488CrossRefGoogle Scholar
  8. 8.
    Teng Z, Sadat U, Brown AJ, Gillard JH (2014) Plaque hemorrhage in carotid artery disease: pathogenesis, clinical and biomechanical considerations. J Biomech 47(4):847–858.  https://doi.org/10.1016/j.jbiomech.2014.01.013 CrossRefGoogle Scholar
  9. 9.
    Saam T, Hetterich H, Hoffmann V, Yuan C, Dichgans M, Poppert H, Koeppel T, Hoffmann U, Reiser MF, Bamberg F (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 CrossRefGoogle Scholar
  10. 10.
    Gupta A, Baradaran H, Schweitzer AD, Kamel H, Pandya A, Delgado D, Dunning A, Mushlin AI, Sanelli PC (2013) Carotid plaque MRI and stroke risk: a systematic review and meta-analysis. Stroke 44(11):3071–3077.  https://doi.org/10.1161/strokeaha.113.002551 CrossRefGoogle Scholar
  11. 11.
    Furie B, Furie BC (2008) Mechanisms of thrombus formation. N Engl J Med 359(9):938–949.  https://doi.org/10.1056/NEJMra0801082 CrossRefGoogle Scholar
  12. 12.
    Anand SS, Yusuf S (1999) Oral anticoagulant therapy in patients with coronary artery disease: a meta-analysis. JAMA 282(21):2058–2067CrossRefGoogle Scholar
  13. 13.
    Bousser MG, Eschwege E, Haguenau M, Lefaucconnier JM, Thibult N, Touboul D, Touboul PJ (1983) “AICLA” controlled trial of aspirin and dipyridamole in the secondary prevention of athero-thrombotic cerebral ischemia. Stroke 14(1):5–14CrossRefGoogle Scholar
  14. 14.
    Hirsh J (1991) Oral anticoagulant drugs. N Engl J Med 324(26):1865–1875.  https://doi.org/10.1056/nejm199106273242606 CrossRefGoogle Scholar
  15. 15.
    Landefeld CS, Beyth RJ (1993) Anticoagulant-related bleeding: clinical epidemiology, prediction, and prevention. Am J Med 95(3):315–328CrossRefGoogle Scholar
  16. 16.
    Serebruany VL, Malinin AI, Eisert RM, Sane DC (2004) Risk of bleeding complications with antiplatelet agents: meta-analysis of 338,191 patients enrolled in 50 randomized controlled trials. Am J Hematol 75(1):40–47.  https://doi.org/10.1002/ajh.10451 CrossRefGoogle Scholar
  17. 17.
    Liem MI, Schreuder FH, van Dijk AC, de Rotte AA, Truijman MT, Daemen MJ, van der Steen AF, Hendrikse J, Nederveen AJ, van der Lugt A, Kooi ME, Nederkoorn PJ (2015) Use of antiplatelet agents is associated with intraplaque hemorrhage on carotid magnetic resonance imaging: the plaque at risk study. Stroke 46(12):3411–3415.  https://doi.org/10.1161/strokeaha.115.008906 CrossRefGoogle Scholar
  18. 18.
    Derksen WJ, Peeters W, Tersteeg C, de Vries JP, de Kleijn DP, Moll FL, van der Wal AC, Pasterkamp G, Vink A (2011) Age and coumarin-type anticoagulation are associated with the occurrence of intraplaque hemorrhage, while statins are associated less with intraplaque hemorrhage: a large histopathological study in carotid and femoral plaques. Atherosclerosis 214(1):139–143.  https://doi.org/10.1016/j.atherosclerosis.2010.10.022 CrossRefGoogle Scholar
  19. 19.
    Shamseer L, Moher D, Clarke M, Ghersi D, Liberati A, Petticrew M, Shekelle P, Stewart LA (2015) Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015: elaboration and explanation. BMJ 350:g7647.  https://doi.org/10.1136/bmj.g7647 CrossRefGoogle Scholar
  20. 20.
    Moynihan RN, Cooke GP, Doust JA, Bero L, Hill S, Glasziou PP (2013) Expanding disease definitions in guidelines and expert panel ties to industry: a cross-sectional study of common conditions in the United States. PLoS Med 10(8):e1001500.  https://doi.org/10.1371/journal.pmed.1001500 CrossRefGoogle Scholar
  21. 21.
    Sun J, Canton G, Balu N, Hippe DS, Xu D, Liu J, Hatsukami TS, Yuan C (2016) Blood pressure is a major modifiable risk factor implicated in pathogenesis of intraplaque hemorrhage: an in vivo magnetic resonance imaging study. Arterioscler Thromb Vasc Biol 36(4):743–749.  https://doi.org/10.1161/atvbaha.115.307043 CrossRefGoogle Scholar
  22. 22.
    Mujaj B, Bos D, Muka T, Lugt AV, Ikram MA, Vernooij MW, Stricker BH, Franco OH (2018) Antithrombotic treatment is associated with intraplaque haemorrhage in the atherosclerotic carotid artery: a cross-sectional analysis of The Rotterdam Study. Eur Heart J 39(36):3369–3376.  https://doi.org/10.1093/eurheartj/ehy433 CrossRefGoogle Scholar
  23. 23.
    Scott McNally J, Yoon HC, Kim SE, Narra KK, McLaughlin MS, Parker DL, Treiman GS (2015) Carotid MRI detection of intraplaque hemorrhage at 3T and 1.5T. J Neuroimaging 25(3):390–396.  https://doi.org/10.1111/jon.12146 CrossRefGoogle Scholar
  24. 24.
    Li X, Vink A, Niessen HW, Kers J, de Boer OJ, Ploegmakers HJ, Tijssen JG, de Winter RJ, van der Wal AC (2014) Total burden of intraplaque hemorrhage in coronary arteries relates to the use of coumarin-type anticoagulants but not platelet aggregation inhibitors. Virchows Arch 465(6):723–729.  https://doi.org/10.1007/s00428-014-1654-y CrossRefGoogle Scholar
  25. 25.
    Vazquez FJ, Gonzalez JP, LeGal G, Carrier M, Gandara E (2016) Risk of major bleeding in patients receiving vitamin K antagonists or low doses of aspirin. A systematic review and meta-analysis. Thromb Res 138:1–6.  https://doi.org/10.1016/j.thromres.2015.12.013 CrossRefGoogle Scholar
  26. 26.
    Virmani R, Kolodgie FD, Burke AP, Finn AV, Gold HK, Tulenko TN, Wrenn SP, Narula J (2005) Atherosclerotic plaque progression and vulnerability to rupture: angiogenesis as a source of intraplaque hemorrhage. Arterioscler Thromb Vasc Biol 25(10):2054–2061.  https://doi.org/10.1161/01.Atv.0000178991.71605.18 CrossRefGoogle Scholar
  27. 27.
    Leithauser B, Mrowietz C, Hiebl B, Pindur G, Jung F (2009) Capillary bleeding under oral anticoagulation. Clin Hemorheol Microcirc 43(1–2):167–171.  https://doi.org/10.3233/ch-2009-1231 Google Scholar
  28. 28.
    Kahn RA, Johnson SA, DeGraff AF (1971) Effects of sodium warfarin on capillary ultrastructure. Am J Pathol 65(1):149–156Google Scholar
  29. 29.
    Toussaint JF, LaMuraglia GM, Southern JF, Fuster V, Kantor HL (1996) Magnetic resonance images lipid, fibrous, calcified, hemorrhagic, and thrombotic components of human atherosclerosis in vivo. Circulation 94(5):932–938CrossRefGoogle Scholar
  30. 30.
    Clarke SE, Hammond RR, Mitchell JR, Rutt BK (2003) Quantitative assessment of carotid plaque composition using multicontrast MRI and registered histology. Magn Reson Med 50(6):1199–1208.  https://doi.org/10.1002/mrm.10618 CrossRefGoogle Scholar
  31. 31.
    Yuan C, Zhao XQ, Hatsukami TS (2002) Quantitative evaluation of carotid atherosclerotic plaques by magnetic resonance imaging. Curr Atheroscler Rep 4(5):351–357CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019
corrected publication 2019

Authors and Affiliations

  1. 1.Department of Radiology, Huashan HospitalFudan UniversityShanghaiChina
  2. 2.Institute of Functional and Molecular Medical ImagingFudan UniversityShanghaiChina

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