Early Rivaroxaban Use After Cardioembolic Stroke May Not Result in Hemorrhagic Transformation

Abstract

Background and Purpose-Early anticoagulation after cardioembolic stroke remains controversial because of the potential for hemorrhagic transformation (HT). We tested the safety and feasibility of initiating rivaroxaban ≤14 days after cardioembolic stroke/transient ischemic attack. Methods-A prospective, open-label study of patients with atrial fibrillation treated with rivaroxaban ≤14 days of transient ischemic attack or ischemic stroke (National Institute of Health Stroke Scale <9). All patients underwent magnetic resonance imaging <24 hours of rivaroxaban initiation and day 7. The primary end point was symptomatic HT at day 7. Results-Sixty patients (mean±SD age 71±19 years, 82% stroke/18% transient ischemic attack) were enrolled. Median (interquartile range) time from onset to rivaroxaban was 3 (5) days. At treatment initiation, median National Institute of Health Stroke Scale was 2 (4), and median diffusion-weighted imaging volume was 7.9 (13.7) mL. At baseline, HT was present in 25 (42%) patients (hemorrhagic infarct [HI]1=19, HI2=6). On follow-up magnetic resonance imaging, no patients developed symptomatic HT. New asymptomatic HI1 developed in 3 patients, and asymptomatic progression from HI1 to HI2 occurred in 5 patients; otherwise, HT remained unchanged at day 7. Conclusions-These data support the safety of rivaroxaban initiation ≤14 days of mild-moderate cardioembolic stroke/ transient ischemic attack. Magnetic resonance imaging evidence of petechial HT, which is common, does not appear to increase the risk of symptomatic HT.

Early Recurrence and Major Bleeding in Patients With Acute Ischemic Stroke and Atrial Fibrillation Treated With Non–Vitamin‐K Oral Anticoagulants (RAF‐NOACs) Study

“…In the RAF study, with enrollment from January 2012 to March 2014, <10% of the patients were treated with non–vitamin K oral anticoagulants (NOACs) 4. Observational studies reported that, if NOACs are started early after an index event, the risk of intracranial bleeding appears to be low 5, 6, 7…”

Early Anticoagulation for Recurrent Ischemic Stroke despite the Presence of Ventricular Bleeding

“…As advanced age is not a contraindication to the use of rivaroxaban [14], he was treated with this DOAC at the dose of 15 mg/die starting 5 days after the index event, despite the presence of intraventricular bleeding occurred after the thrombolytic therapy for the first event. Our results are even more encouraging given that randomized clinical trials with DOACs have excluded acute ischemic stroke patients, and the safety of DOAC administration soon after an index event has only been addressed by observational, prospective, and non-randomized studies [8][9][10][11][12][13]. In particular, in two prospective studies, the treatment with DOACs was commenced after a mean time of four and five days from the index event and no intracranial bleeding was observed during hospitalization [8,13], suggesting the safety of the early use of DOACs after an ischemic episode.…”

“…Based on these data and in consideration of the patient's reduced kidney function, we opted for rivaroxaban 15 mg/die [5,15] despite the presence of intraventricular bleeding and the lack of data on the effects of DOACs in case of such a complication. Moreover, little evidence describes the use of anticoagulation in the presence of HT of ischemic lesions [12]. In a recent prospective study including AF patients treated with rivaroxaban (20 mg in 64% of cases) ≤14 days from TIA or ischemic stroke (NIHSS <9), despite the small sample size (n=60), the magnetic resonance imaging performed at baseline and 7 days after the start of therapy showed that no patient developed sHT of ischemic lesions [12].…”

“…However, randomized clinical trials on DOACs have systematically excluded patients with recent ischemic stroke (<7 days) in whom the risk of sHT is higher [4][5][6][7]. Despite the lack of conclusive clinical evidence, the available data from observational, longitudinal studies suggest that the early use of DOACs is safe and might reduce the risk of sHT [8][9][10][11][12][13]. Therefore, in clinical practice, these agents are perceived as safe and increasingly used even during the first days after ischemic stroke.…”

“…Moreover, little evidence describes the use of anticoagulation in the presence of HT of ischemic lesions [12]. In a recent prospective study including AF patients treated with rivaroxaban (20 mg in 64% of cases) ≤14 days from TIA or ischemic stroke (NIHSS <9), despite the small sample size (n=60), the magnetic resonance imaging performed at baseline and 7 days after the start of therapy showed that no patient developed sHT of ischemic lesions [12]. The case described here presented no HT of ischemic lesions but intraventricular bleeding; still, we observed that the early use of rivaroxaban 15 mg/die, started 5 days after the recurrence of ischemic stroke, did not increase the risk of intracranial bleeding or of lesion HT.…”