Journal of Thrombosis and Thrombolysis

, Volume 42, Issue 1, pp 99–106 | Cite as

Effect of anticoagulation on cardioembolic stroke severity, outcomes and response to intravenous thrombolysis

  • Ignacio Illán-Gala
  • Patricia Martínez-SánchezEmail author
  • Blanca Fuentes
  • Yudy Llamas-Osorio
  • Javier Díaz de Terán
  • Melissa Báez
  • Gerardo Ruiz-Ares
  • Borja Enrique Sanz-Cuesta
  • Manuel Lara-Lara
  • Exuperio Díez-Tejedor


Our objective was to evaluate the effect of anticoagulation on cardioembolic stroke (CS) severity, outcomes, and response to intravenous thrombolysis (IVT). Observational study of CS patients admitted to a Stroke Center (2010–2013). The sample was classified into three groups based on pre-stroke oral anticoagulants (OAC) treatment (all acenocumarol) and the international normalized ratio (INR) on admission: (1) non-anticoagulated or anticoagulated patients with INR <1.5, (2) anticoagulated with INR 1.5–1.9 and (3) anticoagulated with INR ≥2. We compared demographic data, vascular risk factors, symptomatic intracranial hemorrhage, severity on admission (NIHSS) and 3 month outcomes (mRS). Overall 475 patients were included, 47.2 % male, mean age 75.5 (SD 10.7) years old, 31.8 % were on OAC. 76 % belonged to the INR <1.5 group, 13.3 % to the INR 1.5–1.9 and 10.5 % to the INR >2. 35 %of patients received IVT. Multivariate analyses showed that an INR ≥2 on admission was a factor associated with a higher probability of mild stroke (NIHSS <10) (OR 2.026, 95 % CI 1.006–4.082). Previous OAC in general (OR 2.109, 95 % CI 1.173–3.789) as well as INR 1.5–1.9 (OR 3.676, 95 % CI 1.510–8.946) were associated with favorable outcomes (mRS 2). OAC was not related to stroke outcomes in the subgroup of IVT patients. Therapeutic OAC levels are associated with lesser CS severity, and prior OAC treatment with favorable outcomes. In this study, OAC are not related with response to IVT.


Stroke Thrombolysis Antithrombotic therapy Anticoagulation 



The authors thank Juliette Siegfried at for editing the language of the manuscript.

Study funding

This project is supported by research Grants INVICTUS (RD12/0014/0006) (Spanish Neurovascular Network), and Research Institute Carlos III, Ministry Science and Innovation.

Compliance with ethical standards




  1. 1.
    Schwammenthal Y, Bornstein N, Schwammenthal E et al (2010) Relation of effective anticoagulation in patients with atrial fibrillation to stroke severity and survival (from the National Acute Stroke Israeli Survey [NASIS]). Am J Cardiol 105:411–416. doi: 10.1016/j.amjcard.2009.09.050 CrossRefPubMedGoogle Scholar
  2. 2.
    Hylek Go AS, Chang Y et al (2003) Effect of intensity of oral anticoagulation on stroke severity and mortality in atrial fibrillation. N Engl J Med 349:1019–1026. doi: 10.1056/NEJMoa022913 CrossRefPubMedGoogle Scholar
  3. 3.
    O’Donnell M, Oczkowski W, Fang J et al (2006) Preadmission antithrombotic treatment and stroke severity in patients with atrial fibrillation and acute ischaemic stroke: an observational study. Lancet Neurol 5:749–754. doi: 10.1016/S1474-4422(06)70536-1 CrossRefPubMedGoogle Scholar
  4. 4.
    Nakamura A, Ago T, Kamouchi M et al (2013) Intensity of anticoagulation and clinical outcomes in acute cardioembolic stroke: the Fukuoka Stroke Registry. Stroke 44:3239–3242. doi: 10.1161/STROKEAHA.113.002523 CrossRefPubMedGoogle Scholar
  5. 5.
    Ruecker M, Matosevic B, Willeit P et al (2012) Subtherapeutic warfarin therapy entails an increased bleeding risk after stroke thrombolysis. Neurology 79:31–38. doi: 10.1212/WNL.0b013e31825dcdf0 CrossRefPubMedGoogle Scholar
  6. 6.
    Mazya MV, Lees KR, Markus R et al (2013) Safety of intravenous thrombolysis for ischemic stroke in patients treated with warfarin. Ann Neurol 74:266–274. doi: 10.1002/ana.23924 CrossRefPubMedGoogle Scholar
  7. 7.
    Wardlaw JM, Murray V, Berge E, Zoppo GJ (2014) Thrombolysis for acute ischaemic stroke. Cochrane Database Syst Rev 7:CD000213. doi: 10.1002/14651858.CD000213.pub3 PubMedPubMedCentralGoogle Scholar
  8. 8.
    Fuentes B, Díez-Tejedor E, Ortega-Casarrubios MA et al (2006) Consistency of the benefits of stroke units over years of operation: an 8 year effectiveness analysis. Cerebrovasc Dis 21:173–179. doi: 10.1159/000090529 CrossRefPubMedGoogle Scholar
  9. 9.
    (1990) Special report from the National Institute of Neurological Disorders and Stroke. Classification of cerebrovascular diseases III. Stroke. 21:637–676Google Scholar
  10. 10.
    Arboix A, Alio J (2010) Cardioembolic stroke: clinical features, specific cardiac disorders and prognosis. Curr Cardiol Rev 6:150–161. doi: 10.2174/157340310791658730 CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Broderick JP, Palesch YY, Demchuk AM et al (2013) Endovascular therapy after intravenous t-PA versus t-PA alone for stroke. N Engl J Med 368:893. doi: 10.1056/nejmoa1214300 CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Fischer U, Arnold M, Nedeltchev K et al (2005) NIHSS score and arteriographic findings in acute ischemic stroke. Stroke 36:2121–2125. doi: 10.1161/01.STR.0000182099.04994.fc CrossRefPubMedGoogle Scholar
  13. 13.
    Nakajima M, Kimura K, Ogata T (2004) Relationships between angiographic findings and National Institutes of Health stroke scale score in cases of hyperacute carotid ischemic stroke. Am J Neuroradiol 25:238–241PubMedGoogle Scholar
  14. 14.
    Wahlgren N, Ahmed N, Dávalos A, et al (2008) Thrombolysis with alteplase 3–4·5 h after acute ischaemic stroke (SITS-ISTR): an observational study. LancetGoogle Scholar
  15. 15.
    Cruz-Herranz A, Fuentes B, Martínez-Sánchez P et al (2014) Is diabetes an independent risk factor for in-hospital complications after a stroke. J Diabetes. doi: 10.1111/1753-0407.12222 PubMedGoogle Scholar
  16. 16.
    Jauch EC, Saver JL, Adams HP et al (2013) Guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 44:870–947. doi: 10.1161/STR.0b013e318284056a CrossRefPubMedGoogle Scholar
  17. 17.
    Alonso de Leciñana M, Díaz-Guzmán J, Egido JA et al (2013) Endovascular treatment in acute ischaemic stroke. A stroke care plan for the region of Madrid. Neurologia 28:425–434. doi: 10.1016/j.nrl.2012.12.009 CrossRefPubMedGoogle Scholar
  18. 18.
    Pepi M, Evangelista A, Nihoyannopoulos P et al (2010) Recommendations for echocardiography use in the diagnosis and management of cardiac sources of embolism: European Association of Echocardiography (EAE) (a registered branch of the ESC). Eur J Echocardiogr 11:461–476. doi: 10.1093/ejechocard/jeq045 CrossRefPubMedGoogle Scholar
  19. 19.
    Indredavik B, Rohweder G, Lydersen S (2005) Frequency and effect of optimal anticoagulation before onset of ischaemic stroke in patients with known atrial fibrillation. J Intern Med 258:133–144. doi: 10.1111/j.1365-2796.2005.01512.x CrossRefPubMedGoogle Scholar
  20. 20.
    Caso V, Paciaroni M, Agnelli G et al (2006) Prior use of antithrombotic agents and neurological functional outcome at discharge in patients with ischemic stroke. J Thromb Haemost JTH 4:1957–1961. doi: 10.1111/j.1538-7836.2006.02095.x CrossRefPubMedGoogle Scholar
  21. 21.
    European Medicines Agency—Human medicines—Actilyse. In: Accessed 19 July 2015
  22. 22.
    Adams HP, del Zoppo G, Alberts MJ et al (2007) Guidelines for the early management of adults with ischemic stroke: a guideline from the American Heart Association/American Stroke Association. Stroke 38:1655–1711. doi: 10.1161/STROKEAHA.107.181486 CrossRefPubMedGoogle Scholar
  23. 23.
    Frank B, Grotta JC, Alexandrov AV et al (2013) Thrombolysis in stroke despite contraindications or warnings. Stroke 44:727–733. doi: 10.1161/STROKEAHA.112.674622 CrossRefPubMedGoogle Scholar
  24. 24.
    Xian Y, Liang L, Smith EE et al (2012) Risks of intracranial hemorrhage among patients with acute ischemic stroke receiving warfarin and treated with intravenous tissue plasminogen activator. JAMA 307:2600–2608. doi: 10.1001/jama.2012.6756 CrossRefPubMedGoogle Scholar
  25. 25.
    Ay H, Arsava EM, Gungor L et al (2008) Admission international normalized ratio and acute infarct volume in ischemic stroke. Ann Neurol 64:499–506. doi: 10.1002/ana.21456 CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Ignacio Illán-Gala
    • 1
  • Patricia Martínez-Sánchez
    • 1
    Email author
  • Blanca Fuentes
    • 1
  • Yudy Llamas-Osorio
    • 1
  • Javier Díaz de Terán
    • 1
  • Melissa Báez
    • 1
  • Gerardo Ruiz-Ares
    • 1
  • Borja Enrique Sanz-Cuesta
    • 1
  • Manuel Lara-Lara
    • 1
  • Exuperio Díez-Tejedor
    • 1
  1. 1.Department of Neurology and Stroke Center. IdiPAZ Health Research Institute.Hospital Universitario La Paz. Universidad Autónoma de MadridMadridSpain

Personalised recommendations