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Introduction of direct oral anticoagulant within 7 days of stroke onset: a nomogram to predict the probability of 3-month modified Rankin Scale score > 2

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Abstract

In clinical practice, direct oral anticoagulants (DOACs) are often started earlier (≤ 7 days) than in randomized clinical trials after stroke. We aimed to develop a nomogram model incorporating time of DOAC introduction ≤ 7 days of stroke onset in combination with different degrees of stroke radiological/neurological severity at the time of treatment to predict the probability of unfavorable outcome. We conducted a multicenter prospective study including 344 patients who started DOAC 1–7 days after atrial fibrillation-related stroke onset. Computed tomography scan 24–36 h after stroke onset was performed in all patients before starting DOAC. Unfavorable outcome was defined as modified Rankin Scale (mRS) score > 2 at 3 months. Based on multivariate logistic model, the nomogram was generated. We assessed the discriminative performance by using the area under the receiver operating characteristic curve (AUC–ROC) and calibration of risk prediction model by using the Hosmer–Lemeshow test. Onset-to-treatment time for DOAC (OR: 1.21, p = 0.030), NIH Stroke Scale (NIHSS) score at the time of treatment (OR: 1.00 for NIHSS = 0–5; OR: 2.67, p = 0.016 for NIHSS = 6–9; OR: 26.70, p < 0.001 for NIHSS = 10–14; OR: 57.48, p < 0.001 for NIHSS ≥ 15), size infarct (OR: 1.00 for small infarct; OR: 2.26, p = 0.023 for medium infarct; OR: 3.40, p = 0.005 for large infarct), and age ≥ 80 years (OR: 1.96, p = 0.028) remained independent predictors of unfavorable outcome to compose the nomogram. The AUC–ROC of nomogram was 0.858. Calibration was good (p = 2.889 for the Hosmer–Lemeshow test). The combination of onset-to-treatment time of DOAC with stroke radiological/neurological severity at the time of treatment and old age may predict the probability of unfavorable outcome.

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References

  1. Connolly SJ, Ezekowitz MD, Yusuf S et al (2009) Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 361:1139–1151

    Article  PubMed  CAS  Google Scholar 

  2. Granger CB, Alexander JH, McMurray JJ et al (2011) Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med 365:981–992

    Article  PubMed  CAS  Google Scholar 

  3. Patel MR, Mahaffey KW, Garg J et al (2011) Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med 365:883–891

    Article  PubMed  CAS  Google Scholar 

  4. Giugliano RP, Ruff CT, Braunwald E et al (2013) Edoxaban versus warfarin in patients with atrial fibrillation. N Engl J Med 369:2093–2104

    Article  PubMed  CAS  Google Scholar 

  5. Ntaios G, Papavasileiou V, Diener HC et al (2017) Nonvitamin-K-antagonist oral anticoagulants versus warfarin in patients with atrial fibrillation and previous stroke or transient ischemic attack: an updated systematic review and meta-analysis of randomized controlled trials. Int J Stroke 12:589–596

    Article  PubMed  Google Scholar 

  6. Abdul-Rahim AH, Fulton RL et al (2015) Association of improved outcome in acute ischaemic stroke patients with atrial fibrillation who receive early antithrombotic therapy: analysis from VISTA. Eur J Neurol 22:1048–1055

    Article  PubMed  CAS  Google Scholar 

  7. Cappellari M, Bovi P (2017) Early use of direct oral anticoagulants after TIA/stroke in patients with atrial fibrillation: a 2016 update. J Thromb Thrombolysis 43:302–305

    Article  PubMed  Google Scholar 

  8. Paciaroni M, Agnelli G, Caso V et al (2017) Prediction of early recurrent thromboembolic event and major bleeding in patients with acute stroke and atrial fibrillation by a risk stratification schema: The ALESSA score study. Stroke 48:726–732

    Article  PubMed  Google Scholar 

  9. Saver JL, Altman H (2012) Relationship between neurologic deficit severity and final functional outcome shifts and strengthens during first hours after onset. Stroke 43:1537–1541

    Article  PubMed  PubMed Central  Google Scholar 

  10. Lip GY, Nieuwlaat R, Pisters R, Lane DA, Crijns HJ (2010) Refining clinical risk stratification for predicting stroke and thromboembolism in atrial fibrillation using a novel risk factor-based approach: the Euro Heart Survey on atrial fibrillation. Chest 137:263–272

    Article  PubMed  Google Scholar 

  11. Pisters R, Lane DA, Nieuwlaat R, de Vos CB, Crijns HJ, Lip GY (2010) A novel user-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in patients with atrial fibrillation: the Euro Heart Survey. Chest 138:1093–1100

    Article  PubMed  Google Scholar 

  12. Larrue V, Von Kummar R, del Zoppo G, Bluhmki E (1997) Haemorrhagic transformation in acute ischaemic stroke. Potential contributing factors in the European Cooperative Acute Stroke Study. Stroke 28:957–960

    Article  PubMed  CAS  Google Scholar 

  13. Jehi L, Yardi R, Chagin K et al (2015) Development and validation of nomograms to provide individualised predictions of seizure outcomes after epilepsy surgery: a retrospective analysis. Lancet Neurol 14:283–290

    Article  PubMed  Google Scholar 

  14. Callegaro D, Miceli R, Bonvalot S et al (2016) Development and external validation of two nomograms to predict overall survival and occurrence of distant metastases in adults after surgical resection of localised soft-tissue sarcomas of the extremities: a retrospective analysis. Lancet Oncol 17:671–680

    Article  PubMed  Google Scholar 

  15. Hijazi Z, Oldgren J, Lindbäck J et al (2016) The novel biomarker-based ABC (age, biomarkers, clinical history)-bleeding risk score for patients with atrial fibrillation: a derivation and validation study. Lancet 387:2302–2311

    Article  PubMed  CAS  Google Scholar 

  16. Cappellari M, Turcato G, Forlivesi S et al (2018) The START nomogram for individualized prediction of the probability of unfavorable outcome after intravenous thrombolysis for stroke. Int J Stroke 1:1747493018765490. https://doi.org/10.1177/1747493018765490

    Article  Google Scholar 

  17. Cappellari M, Turcato G, Forlivesi S et al (2018) STARTING-SICH nomogram to predict symptomatic intracerebral hemorrhage after intravenous thrombolysis for stroke. Stroke 49:397–404

    Article  PubMed  Google Scholar 

  18. Nolte CH, Albach FN, Heuschmann PU et al (2012) Silent new DWI lesions within the first week after stroke. Cerebrovasc Dis 33:248–254

    Article  PubMed  Google Scholar 

  19. Heidbuchel H, Verhamme P, Alings M et al (2015) Updated European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist anticoagulants in patients with non-valvular atrial fibrillation. Europace 17:1467–1507

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Neuroscience, Azienda Ospedaliera Universitaria Integrata, Piazzale A. Stefani 1, 37126, Verona, Italy

    Manuel Cappellari, Stefano Forlivesi, Nicola Micheletti, Giampaolo Tomelleri, Bruno Bonetti & Paolo Bovi

  2. Emergency Department, Hospital San Bonifacio, Verona, Italy

    Gianni Turcato

  3. Department of Neuroscience, Azienda Sanitaria Universitaria Integrata, Udine, Italy

    Giovanni Merlino & Carolina Gentile

  4. Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta, Milano, Italy

    Roberto Eleopra

  5. Ospedale S. Maria della Misericordia, Rovigo, Italy

    Monia Russo & Roberto L’Erario

  6. Ospedale Sacro Cuore, Negrar, Italy

    Alessandro Adami

  7. Ospedale S. Maria dei Battuti, Conegliano, Italy

    Anna Gaudenzi & Sandro Bruno

Authors
  1. Manuel Cappellari
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  2. Gianni Turcato
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  3. Stefano Forlivesi
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  4. Nicola Micheletti
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  5. Giampaolo Tomelleri
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  6. Bruno Bonetti
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  7. Giovanni Merlino
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  8. Roberto Eleopra
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  9. Monia Russo
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  10. Roberto L’Erario
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  11. Alessandro Adami
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  12. Carolina Gentile
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  13. Anna Gaudenzi
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  14. Sandro Bruno
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  15. Paolo Bovi
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Corresponding author

Correspondence to Manuel Cappellari.

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The authors declare that they have no conflict of interest.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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Cappellari, M., Turcato, G., Forlivesi, S. et al. Introduction of direct oral anticoagulant within 7 days of stroke onset: a nomogram to predict the probability of 3-month modified Rankin Scale score > 2. J Thromb Thrombolysis 46, 292–298 (2018). https://doi.org/10.1007/s11239-018-1700-8

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  • DOI: https://doi.org/10.1007/s11239-018-1700-8

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