@article{discovery10043575,
          number = {3},
            year = {2018},
           month = {March},
         journal = {Annals of Neurology},
           pages = {451--459},
            note = {{\copyright} 2018 American Neurological Association. This version is the author accepted manuscript. For information on re-use, please refer to the publisher's terms and conditions.},
          volume = {83},
           title = {Rivaroxaban plasma levels in acute ischemic stroke and intracerebral hemorrhage},
          author = {Seiffge, DJ and K{\"a}gi, G and Michel, P and Fischer, U and B{\'e}jot, Y and Wegener, S and Zedde, M and Turc, G and Cordonnier, C and Sandor, PS and Rodier, G and Zini, A and Cappellari, M and Sch{\"a}delin, S and Polymeris, AA and Werring, D and Thilemann, S and Maestrini, I and Berge, E and Traenka, C and Vehoff, J and De Marchis, GM and Kapauer, M and Peters, N and Sirimarco, G and Bonati, LH and Arnold, M and Lyrer, PA and De Maistre, E and Luft, A and Tsakiris, DA and Engelter, ST and NOACISP study group, .},
        abstract = {OBJECTIVE: Information about Rivaroxaban plasma levels (RivLev) may guide treatment decisions in patients with acute ischemic stroke (AIS) and intracerebral hemorrhage (ICH) taking rivaroxaban. METHODS: In a multicenter registry-based study (Novel-Oral-Anticoagulants-In-Stroke-Patients collaboration;NOACISP;ClinicalTrials.gov:NCT02353585) of patients with stroke while taking rivaroxaban, we compared RivLev in patients with AIS and ICH. We determined how many AIS-patients had RivLev{$\leq$}100ng/ml, indicating possible eligibility for thrombolysis and how many ICH-patients had RivLev{$\ge$}75ng/ml, possibly eligible for the use of specific reversal agents. We explored factors associated with RivLev (Spearman correlation; regression models) and studied the sensitivity and specificity of INR-thresholds to substitute RivLevs using cross tables and ROC curves. RESULTS: Among 241 patients (median age 80 years[IQR73-84], median time-from-onset-to-admission 2 hours[IQR1-4.5hours], median RivLev 89ng/ml[31-194]), 190 had AIS and 51 had ICH. RivLev were similar in AIS-patients (82ng/ml[IQR30-202] and ICH-patients (102ng/ml[IQR 51-165]; p=0.24). Trough RivLev({$\leq$}137ng/ml) occurred in 126/190 (66.3\%) AIS- and 34/51 (66.7\%) ICH-patients. Among AIS-patients, 108/190 (56.8\%) had RivLev{$\leq$}100ng/ml. In ICH-patients 33/51(64.7\%) had RivLev{$\ge$}75ng/ml. RivLev were associated with rivaroxaban dosage, inversely with renal function and time-since-last-intake (each p{\ensuremath{<}}.05). INR{$\leq$}1.0 had a specificity of 98.9\% and a sensitivity of 25.7\% to predict RivLev{$\leq$}100ng/ml. INR{$\ge$}1.4 had a sensitivity of 59.3\% and specificity of 90.1\% to predict RivLev{$\ge$}75ng/ml. INTERPRETATION: RivLev did not differ between patients with AIS and ICH. Half of the patients with AIS under Rivaroxaban had RivLev low enough to consider thrombolysis. In ICH-patients, 2/3 had RivLev high enough to meet the eligibility for the use of a specific reversal agent. INR-thresholds perform poor to inform treatment decisions in individual patients. This article is protected by copyright. All rights reserved.},
             url = {https://doi.org/10.1002/ana.25165},
            issn = {1531-8249}
}