Skip to main content
SpringerLink
Log in

Impact of pre-admission treatment with non-vitamin K oral anticoagulants on stroke severity in patients with acute ischemic stroke

  • Published:
Journal of Thrombosis and Thrombolysis Aims and scope Submit manuscript

Abstract

Background

Non-vitamin K antagonist oral anticoagulants (NOACs) have gained increasing importance for stroke prevention in patients with non-valvular atrial fibrillation (AF). With changing prescription practice, among other factors, clinicians can expect to see rising numbers of patients with ischemic stroke and pre-existing NOAC therapy. Few data exist regarding a potential impact of NOAC on stroke severity and outcome.

Aims

To evaluate the impact of pre-admission NOAC therapy on ischemic stroke severity.

Methods

Retrospective analysis of medical data of 376 patients with newly detected AF or known AF with either no pre-admission oral anticoagulation (n = 277) or existing NOAC therapy (n = 99; Apixaban, n = 33, Dabigatran, n = 16; Edoxaban, n = 1; Rivaroxaban, n = 49) consecutively admitted for acute ischemic stroke between January 2015 and December 2016.

Results

Patients with pre-admission NOAC had significantly more often experienced a prior stroke than patients not on NOAC therapy (45.5 vs. 18.4%, p < 0.001) and were significantly more frequently non-smokers (1.0 vs. 7.2%, p = 0.021). Significantly more patients without pre-admission NOAC received thrombolysis (33.8 vs. 8.1%, p < 0.001). Pre-admission NOAC therapy was associated with significantly lower NIHSS and mRS scores upon admission (median NIHSS score 6 vs. 10, p = 0.018, median mRS score 4 vs. 5, p = 0.035) and trend-level lower NIHSS scores at discharge (median NIHSS score 3 vs. 5, p = 0.057). There were no differences regarding the frequency of symptomatic intracerebral hemorrhage between NOAC and non-NOAC patients (p > 0.05).

Conclusions

We report a positive impact of pre-admission NOAC on ischemic stroke severity, which is particularly remarkable in light of the increased prevalence of prior stroke and lower rates of thrombolysis in this patient population.

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

Fig. 1

Similar content being viewed by others

References

  1. Hajat C, Heuschmann PU, Coshall C et al (2011) Incidence of aetiological subtypes of stroke in a multi-ethnic population based study: the South London Stroke Register. J Neurol Neurosurg Psychiatry 82:527–533. https://doi.org/10.1136/jnnp.2010.222919

    Article  PubMed  Google Scholar 

  2. Dulli DA, Stanko H, Levine RL (2003) Atrial fibrillation is associated with severe acute ischemic stroke. Neuroepidemiology 22:118–123

    Article  PubMed  Google Scholar 

  3. Holbrook AM, Pereira JA, Labiris R et al (2005) Systematic overview of warfarin and its drug and food interactions. Arch Intern Med 165:1095–1106. https://doi.org/10.1001/archinte.165.10.1095

    Article  CAS  PubMed  Google Scholar 

  4. Ruff CT, Giugliano RP, Braunwald E et al (2014) Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials. Lancet 383:955–962. https://doi.org/10.1016/S0140-6736(13)62343-0

    Article  CAS  PubMed  Google Scholar 

  5. Bassand J-P, Accetta G, Camm AJ et al (2016) Two-year outcomes of patients with newly diagnosed atrial fibrillation: results from GARFIELD-AF. Eur Heart J 37:2882–2889. https://doi.org/10.1093/eurheartj/ehw233

    Article  PubMed  PubMed Central  Google Scholar 

  6. Loo SY, Dell’Aniello S, Huiart L, Renoux C (2017) Trends in the prescription of novel oral anticoagulants in UK primary care. Br J Clin Pharmacol 44:D1054–D2106. https://doi.org/10.1111/bcp.13299

    Google Scholar 

  7. Connolly SJ, Ezekowitz MD, Yusuf S et al (2009) Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 361:1139–1151. https://doi.org/10.1056/NEJMoa0905561

    Article  CAS  PubMed  Google Scholar 

  8. Giugliano RP, Ruff CT, Braunwald E et al (2013) Edoxaban versus warfarin in patients with atrial fibrillation. N Engl J Med 369:2093–2104. https://doi.org/10.1056/NEJMoa1310907

    Article  CAS  PubMed  Google Scholar 

  9. Granger CB, Alexander JH, McMurray JJV et al (2011) Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med 365:981–992. https://doi.org/10.1056/NEJMoa1107039

    Article  CAS  PubMed  Google Scholar 

  10. Patel MR, Mahaffey KW, Garg J et al (2011) Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med 365:883–891. https://doi.org/10.1056/NEJMoa1009638

    Article  CAS  PubMed  Google Scholar 

  11. Zoni-Berisso M, Lercari F, Carazza T, Domenicucci S (2014) Epidemiology of atrial fibrillation: European perspective. Clin Epidemiol 6:213–220. https://doi.org/10.2147/CLEP.S47385

    Article  PubMed  PubMed Central  Google Scholar 

  12. Hart RG, Diener H-C, Connolly SJ (2014) Embolic strokes of undetermined source: support for a new clinical construct—authors’ reply. Lancet Neurol 13:967. https://doi.org/10.1016/S1474-4422(14)70197-8

    Article  PubMed  Google Scholar 

  13. Hylek EM, 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. https://doi.org/10.1056/NEJMoa022913

    Article  CAS  PubMed  Google Scholar 

  14. 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. https://doi.org/10.1016/S1474-4422(06)70536-1

    Article  PubMed  Google Scholar 

  15. 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]). AJC 105:411–416. https://doi.org/10.1016/j.amjcard.2009.09.050

    Article  Google Scholar 

  16. Hellwig S, Grittner U, Audebert H et al (2017) Non-vitamin K-dependent oral anticoagulants have a positive impact on ischaemic stroke severity in patients with atrial fibrillation. EP Europace. https://doi.org/10.1093/europace/eux087

    PubMed  Google Scholar 

  17. Tomita H, Hagii J, Metoki N et al (2015) Severity and functional outcome of patients with cardioembolic stroke occurring during non-vitamin K antagonist oral anticoagulant treatment. J Stroke Cerebrovasc Dis 24:1430–1437. https://doi.org/10.1016/j.jstrokecerebrovasdis.2015.03.004

    Article  PubMed  Google Scholar 

  18. Xian Y, O’Brien EC, Liang L et al (2017) Association of preceding antithrombotic treatment with acute ischemic stroke severity and in-hospital outcomes among patients with atrial fibrillation. JAMA 317:1057–1067. https://doi.org/10.1001/jama.2017.1371

    Article  PubMed  Google Scholar 

  19. Hacke W, Kaste M, Fieschi C et al (1995) Intravenous thrombolysis with recombinant tissue plasminogen activator for acute hemispheric stroke. The European Cooperative Acute Stroke Study (ECASS). JAMA 274:1017–1025

    Article  CAS  PubMed  Google Scholar 

  20. Hacke W, Kaste M, Bluhmki E et al (2008) Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. N Engl J Med 359:1317–1329. https://doi.org/10.1056/NEJMoa0804656

    Article  CAS  PubMed  Google Scholar 

  21. Xian Y, Federspiel JJ, Hernandez AF et al (2017) Use of intravenous recombinant tissue plasminogen activator in patients with acute ischemic stroke who take non-vitamin K antagonist oral anticoagulants before StrokeClinical Perspective. Circulation 135:1024–1035. https://doi.org/10.1161/CIRCULATIONAHA.116.023940

    Article  CAS  PubMed  Google Scholar 

  22. Tziomalos K, Giampatzis V, Bouziana SD et al (2015) Adequacy of preadmission oral anticoagulation with vitamin K antagonists and ischemic stroke severity and outcome in patients with atrial fibrillation. J Thromb Thrombolysis 41:336–342. https://doi.org/10.1007/s11239-015-1262-y

    Article  Google Scholar 

  23. Purrucker JC, Haas K, Rizos T et al (2017) Coagulation testing in acute ischemic stroke patients taking non-vitamin K antagonist oral anticoagulants. Stroke 48:152–158. https://doi.org/10.1161/STROKEAHA.116.014963

    Article  CAS  PubMed  Google Scholar 

  24. Ives SP, Heuschmann PU, Wolfe CDA, Redfern J (2008) Patterns of smoking cessation in the first 3 years after stroke: the South London Stroke Register. Eur J Cardiovasc Prev Rehabil 15:329–335. https://doi.org/10.1097/HJR.0b013e3282f37a58

    Article  PubMed  Google Scholar 

  25. Micha R, Peñalvo JL, Cudhea F et al (2017) Association between dietary factors and mortality from heart disease, stroke, and type 2 diabetes in the United States. JAMA 317:912–924. https://doi.org/10.1001/jama.2017.0947

    Article  PubMed  PubMed Central  Google Scholar 

  26. Rist PM, Capistrant BD, Mayeda ER et al (2017) Physical activity, but not body mass index, predicts less disability before and after stroke. Neurology 88:1718–1726. https://doi.org/10.1212/WNL.0000000000003888

    Article  PubMed  Google Scholar 

  27. Wilson D, Seiffge DJ, Traenka C et al (2017) Outcome of intracerebral hemorrhage associated with different oral anticoagulants. Neurology 88:1693–1700. https://doi.org/10.1212/WNL.0000000000003886

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Dittmeier M, Wassmuth K, Schuhmann MK et al (2016) Dabigatran etexilate reduces thrombin-induced inflammation and thrombus formation in experimental ischemic stroke. Curr Neurovasc Res 13:199–206

    Article  CAS  PubMed  Google Scholar 

  29. Dittmeier M, Kraft P, Schuhmann MK et al (2016) Pretreatment with rivaroxaban attenuates stroke severity in rats by a dual antithrombotic and anti-inflammatory mechanism. Thromb Haemost 115:835–843. https://doi.org/10.1160/TH15-08-0631

    Article  PubMed  Google Scholar 

  30. Chen T, Wang J, Li C et al (2014) Nafamostat mesilate attenuates neuronal damage in a rat model of transient focal cerebral ischemia through thrombin inhibition. Sci Rep 4:5531. https://doi.org/10.1038/srep05531

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Wolzt M, Eriksson UG, Gouya G et al (2012) Effect on perfusion chamber thrombus size in patients with atrial fibrillation during anticoagulant treatment with oral direct thrombin inhibitors, AZD0837 or ximelagatran, or with vitamin K antagonists. Thromb Res 129:e83–e91. https://doi.org/10.1016/j.thromres.2011.08.018

    Article  CAS  PubMed  Google Scholar 

  32. Wolzt M, Gouya G, Kapiotis S et al (2013) Open-label, randomized study of the effect of rivaroxaban with or without acetylsalicylic acid on thrombus formation in a perfusion chamber. Thromb Res 132:240–247. https://doi.org/10.1016/j.thromres.2013.05.019

    Article  CAS  PubMed  Google Scholar 

  33. Belyaev AV, Panteleev MA, Ataullakhanov FI (2015) Threshold of microvascular occlusion: injury size defines the thrombosis scenario. Biophys J 109:450–456. https://doi.org/10.1016/j.bpj.2015.06.019

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Jackson SP, Nesbitt WS, Westein E (2009) Dynamics of platelet thrombus formation. J Thromb Haemost 7(Suppl 1):17–20. https://doi.org/10.1111/j.1538-7836.2009.03401.x

    Article  CAS  PubMed  Google Scholar 

  35. Fukushima K, Fukushima N, Kato K et al (2016) Correlation between left atrial appendage morphology and flow velocity in patients with paroxysmal atrial fibrillation. Eur Heart J Cardiovasc Imaging 17:59–66. https://doi.org/10.1093/ehjci/jev117

    PubMed  Google Scholar 

  36. Di Biase L, Santangeli P, Anselmino M et al (2012) Does the left atrial appendage morphology correlate with the risk of stroke in patients with atrial fibrillation? Results from a multicenter study. J Am Coll Cardiol 60:531–538. https://doi.org/10.1016/j.jacc.2012.04.032

    Article  PubMed  Google Scholar 

  37. Demaerschalk BM, Kleindorfer DO, Adeoye OM et al (2016) Scientific rationale for the inclusion and exclusion criteria for intravenous alteplase in acute ischemic stroke. Stroke 47:581–641. https://doi.org/10.1161/STR.0000000000000086

    Article  PubMed  Google Scholar 

  38. Goyal M, Menon BK, van Zwam WH et al (2016) Endovascular thrombectomy after large-vessel ischaemic stroke: a meta-analysis of individual patient data from five randomised trials. Lancet 387:1723–1731. https://doi.org/10.1016/S0140-6736(16)00163-X

    Article  PubMed  Google Scholar 

  39. De Marchis GM, Jung S, Colucci G et al (2011) Intracranial hemorrhage, outcome, and mortality after intra-arterial therapy for acute ischemic stroke in patients under oral anticoagulants. Stroke 42:3061–3066. https://doi.org/10.1161/STROKEAHA.111.615476

    Article  PubMed  Google Scholar 

  40. Rebello LC, Haussen DC, Belagaje S et al (2015) Endovascular treatment for acute ischemic stroke in the setting of anticoagulation. Stroke 46:3536–3539. https://doi.org/10.1161/STROKEAHA.115.011285

    Article  CAS  PubMed  Google Scholar 

  41. Dorn F, Prothmann S, Patzig M et al (2016) Stent retriever thrombectomy in patients who are ineligible for intravenous thrombolysis: a multicenter retrospective observational study. AJNR Am J Neuroradiol 37:305–310. https://doi.org/10.3174/ajnr.A4520

    Article  CAS  PubMed  Google Scholar 

  42. Wilke T, Groth A, Pfannkuche M et al (2015) Real life anticoagulation treatment of patients with atrial fibrillation in Germany: extent and causes of anticoagulant under-use. J Thromb Thrombolysis 40:1–11. https://doi.org/10.1007/s11239-014-1136-8

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Neurology, Universitätsmedizin Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany

    Carolin Hoyer, Alexandra Filipov, Kristina Szabo, Anne Ebert & Angelika Alonso

  2. Department of Neuroradiology, Universitätsmedizin Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany

    Eva Neumaier-Probst

Authors
  1. Carolin Hoyer
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Alexandra Filipov
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Eva Neumaier-Probst
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kristina Szabo
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Anne Ebert
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Angelika Alonso
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Carolin Hoyer.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Hoyer, C., Filipov, A., Neumaier-Probst, E. et al. Impact of pre-admission treatment with non-vitamin K oral anticoagulants on stroke severity in patients with acute ischemic stroke. J Thromb Thrombolysis 45, 529–535 (2018). https://doi.org/10.1007/s11239-018-1634-1

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11239-018-1634-1

Keywords

Search

Navigation