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Rivaroxaban plasma levels in acute ischemic stroke and intracerebral hemorrhage

David J Seiffge, Georg Kägi, Patrik Michel, Urs Fischer, Yannick Béjot, Susanne Wegener, Marialuisa Zedde, Guillaume Turc, Charlotte Cordonnier, Peter S Sandor, Gilles Rodier, Andrea Zini, Manuel Cappellari, Sabine Schädelin, Alexandros A Polymeris, David Werring, Sebastian Thilemann, Ilaria Maestrini, Eivind Berge, Christopher Traenka, Jochen Vehoff, Gian Marco De Marchis, Monika Kapauer, Nils Peters, Gaia Sirimarco, Leo H Bonati, Marcel Arnold, Philippe A Lyrer, Emmanuel De Maistre, Andreas Luft, Dimtrios A Tsakiris, Stefan T Engelter & 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≤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 RivLevoccurred 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.
   
citation Seiffge D J, Kägi G, Michel P, Fischer U, Béjot Y, Wegener S, Zedde M, Turc G, Cordonnier C, Sandor P S, Rodier G, Zini A, Cappellari M, Schädelin S, Polymeris A A, Werring D, Thilemann S, Maestrini I, Berge E, Traenka C, Vehoff J, De Marchis G M, Kapauer M, Peters N, Sirimarco G, Bonati L H, Arnold M, Lyrer P A, De Maistre E, Luft A, Tsakiris D A, Engelter S T, NOACISP Study Group . Rivaroxaban plasma levels in acute ischemic stroke and intracerebral hemorrhage. Ann Neurol 2018;.
   
type journal paper/review (English)
date of publishing 02-02-2018
journal title Ann Neurol
ISSN electronic 1531-8249
PubMed 29394504
DOI 10.1002/ana.25165