Abstract
Introduction
The aim of this study is to compare the “1-2-3-4-day” rule applied to stroke severity at baseline versus at 24 h to start DOAC for AF within 7 days from symptom onset.
Patients and methods
We conducted a prospective cohort observational study based on 433 consecutive AF-related stroke patients starting DOAC within 7 days from symptom onset. Four groups were identified according to the timing of DOAC introduction: 2-day, 3-day, 4-day, and 5–7-day.
Results
Three models of multivariate ordinal regression including unbalanced variables among four groups (enrolment year, dyslipidemia, known AF, thrombolysis, thrombectomy, hemorrhagic transformation, DOAC type) were used to estimate the association of neurological severity categories (reference: NIHSS > 15) at baseline (Brant test: 0.818), at 24 h (Brant test: 0.997), and radiological severity categories (reference: major infarct) at 24 h (Brant test: 0.902) in the direction of earlier DOAC introduction on days (from 5–7-day to 2-day). Number of deaths was higher in early DOAC group than in late DOAC group according to the “1-2-3-4-day” rule (5.4% versus 1.3%, 6.8% versus 1.1%, and 4.2% versus 1.7% when it was applied to baseline neurological severity, 24-h neurological and radiological severity, respectively), but no significant difference was found and deaths were not caused by early DOAC introduction. Rates of ischemic stroke and intracranial hemorrhage were not different between early and late DOAC groups.
Conclusions
The application of “1-2-3-4-day” rule to start DOAC for AF within 7 days from symptom onset differed when applied to baseline neurological stroke severity versus 24-h neurological and radiological severity, but safety and effecacy are similar.
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References
Kirchhof P, Benussi S, Kotecha D et al (2016) 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur Heart J 37:2893–2962
Kimura S, Toyoda K, Yoshimura S et al (2022) Practical "1-2-3-4-Day" rule for starting direct oral anticoagulants after ischemic stroke with atrial fibrillation: combined hospital-based cohort study. Stroke 53:1540–1549
Toyoda K, Arihiro S, Todo K et al (2015) Trends in oral anticoagulant choice for acute stroke patients with nonvalvular atrial fibrillation in Japan: the SAMURAI-NVAF study. Int J Stroke 10:836–842
Yasaka M, Minematsu K, Toyoda K et al (2019) Rivaroxaban administration after acute ischemic stroke: The RELAXED study. PLoS One 14:e0212354
Paciaroni M, Agnelli G, Falocci N et al (2015) Early recurrence and cerebral bleeding in patients with acute ischemic stroke and atrial fibrillation: effect of anticoagulation and its timing: The RAF Study. Stroke 46:2175–2182
Paciaroni M, Agnelli G, Falocci N et al (2017) Early recurrence and major bleeding in patients with acute ischemic stroke and atrial fibrillation treated with Non-Vitamin-K Oral Anticoagulants (RAF-NOACs) Study. J Am Heart Assoc 6:e007034
Charidimou A, Wilson D, Shakeshaft C et al (2015) The clinical relevance of microbleeds in stroke study (CROMIS-2): rationale, design, and methods. Int J Stroke. 10(Suppl A100):155–161
Wilson D, Ambler G, Shakeshaft C et al (2018) CROMIS-2 collaborators. Cerebral microbleeds and intracranial haemorrhage risk in patients anticoagulated for atrial fibrillation after acute ischaemic stroke or transient ischaemic attack (CROMIS-2): a multicentre observational cohort study. Lancet Neurol 17:539–547
Seiffge DJ, Traenka C, Polymeris A et al (2016) Early start of DOAC after ischemic stroke: risk of intracranial hemorrhage and recurrent events. Neurology 87:1856–1862
Cappellari M, Carletti M, Danese A et al (2016) Early introduction of direct oral anticoagulants in cardioembolic stroke patients with non-valvular atrial fibrillation. J Thromb Thrombolysis 42:393–398
Macha K, Volbers B, Bobinger T et al (2016) Early initiation of anticoagulation with direct oral anticoagulants in patients after transient ischemic attack or ischemic stroke. J Stroke Cerebrovasc Dis 25:2317–2321
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
Larrue V, Von Kummar R, del Zoppo G, at al. (1997) Haemorrhagic transformation in acute ischaemic stroke. Potential contributing factors in the European Cooperative Acute Stroke Study. Stroke 28:957–960
Åsberg S, Hijazi Z, Norrving B, et. Al. (2017) Timing of oral anticoagulant therapy in acute ischemic stroke with atrial fibrillation: study protocol for a registry-based randomised controlled trial. Trials 18:581
Fischer U, Trelle S, Branca M et al (2022) Early versus late initiation of direct oral anticoagulants in post-ischaemic stroke patients with atrial fibrillatioN (ELAN): protocol for an international, multicentre, randomised-controlled, two-arm, open, assessor-blinded trial. Eur Stroke J 7:487–495
Paciaroni M, Agnelli G, Corea F, al. (2008) Early hemorrhagic transformation of brain infarction: rate, predictive factors, and influence on clinical outcome: results of a prospective multicenter study. Stroke 39:2249–2256
Arihiro S, Todo K, Koga M et al (2016) Three-month risk-benefit profile of anticoagulation after stroke with atrial fibrillation:the SAMURAI-Nonvalvular Atrial Fibrillation (NVAF) study. Int J Stroke 11:565–574
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The present study was in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.
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Manuel Cappellari received consultancy or advisory board fees or speaker’s honoraria from Boehringer Ingelheim, Pfizer/Bristol Meyer Squibb, and Daiichi Sankyo. All other authors report no conflicts of interest.
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ESM 1:
Supplemental Table 1. Numbers of patients in each neurological stroke severity category at baseline and at 24 hours per infarct sizes at 24 hours. Supplemental Table 2. Relationship between early (versus late) DOAC introduction and events. Supplemental Figure 1. Distribution of days according to the “1-2-3-4-day” rule for each stroke severity category. Supplemental Figure 2. Interaction tree generated by the first cluster analysis including demographic, clinical, and radiological variables. Supplemental Figure 3. Interaction tree generated by the first cluster analysis including demographic, clinical, and radiological variables plus baseline neurological severity and 24-hour neurological and radiological severity.
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Cappellari, M., Emiliani, A., Zivelonghi, C. et al. Application of the “1-2-3-4-day” rule to stroke severity at baseline versus at 24 h to start direct oral anticoagulant for atrial fibrillation within 7 days from symptom onset. Neurol Sci 44, 2821–2829 (2023). https://doi.org/10.1007/s10072-023-06717-9
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DOI: https://doi.org/10.1007/s10072-023-06717-9