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

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.