Nils Peters, Emmanuel De Maistre, Manuel Cappellari, Leo H. Bonati, David J. Seiffge, Eivind Berge, Patrik Michel, Dimtrios A. Tsakiris, Monika Kapauer, Christopher Traenka, Georg Kägi, Philippe A. Lyrer, Marcel Arnold, Alexandros A. Polymeris, Susanne Wegener, David Werring, Gian Marco De Marchis, Sabine Schädelin, Marialuisa Zedde, Andreas Luft, Guillaume Turc, Yannick Béjot, , Gaia Sirimarco, Jochen Vehoff, Gilles Rodier, Ilaria Maestrini, Charlotte Cordonnier, Andrea Zini, Urs Fischer, Sebastian Thilemann, Peter S. Sandor, Stefan T. Engelter
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.
