TY  - JOUR
IS  - 3
N1  - © 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.
TI  - Rivaroxaban plasma levels in acute ischemic stroke and intracerebral hemorrhage
AV  - public
VL  - 83
SP  - 451
Y1  - 2018/03//
EP  - 459
JF  - Annals of Neurology
A1  - Seiffge, DJ
A1  - Kägi, G
A1  - Michel, P
A1  - Fischer, U
A1  - Béjot, Y
A1  - Wegener, S
A1  - Zedde, M
A1  - Turc, G
A1  - Cordonnier, C
A1  - Sandor, PS
A1  - Rodier, G
A1  - Zini, A
A1  - Cappellari, M
A1  - Schädelin, S
A1  - Polymeris, AA
A1  - Werring, D
A1  - Thilemann, S
A1  - Maestrini, I
A1  - Berge, E
A1  - Traenka, C
A1  - Vehoff, J
A1  - De Marchis, GM
A1  - Kapauer, M
A1  - Peters, N
A1  - Sirimarco, G
A1  - Bonati, LH
A1  - Arnold, M
A1  - Lyrer, PA
A1  - De Maistre, E
A1  - Luft, A
A1  - Tsakiris, DA
A1  - Engelter, ST
A1  - NOACISP study group, .
N2  - 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?100ng/ml, indicating possible eligibility for thrombolysis and how many ICH-patients had RivLev?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(?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?100ng/ml. In ICH-patients 33/51(64.7%) had RivLev?75ng/ml. RivLev were associated with rivaroxaban dosage, inversely with renal function and time-since-last-intake (each p<.05). INR?1.0 had a specificity of 98.9% and a sensitivity of 25.7% to predict RivLev?100ng/ml. INR?1.4 had a sensitivity of 59.3% and specificity of 90.1% to predict RivLev?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.
ID  - discovery10043575
UR  - https://doi.org/10.1002/ana.25165
SN  - 1531-8249
ER  -