Didier Leys1, Yannick Hommet2, Clémence Jacquet2, Solène Moulin2, Igor Sibon2, Jean-Louis Mas2, Thierry Moulin2, Maurice Giroud2, Sharmila Sagnier2, Charlotte Cordonnier2, Elisabeth Medeiros de Bustos2, Guillaume Turc2, Thomas Ronzière2, Yannick Bejot2, Olivier Detante2, Thavarak Ouk2, Anne-Marie Mendyk2, Pascal Favrole2, Mathieu Zuber2, Aude Triquenot-Bagan2, Ozlem Ozkul-Wermester2, Francisco Macian Montoro2, Chantal Lamy2, Anthony Faivre2, Laurent Lebouvier2, Camille Potey2, Mathilde Poli2, Hilde Hénon2, Pauline Renou2, Nelly Dequatre-Ponchelle2, Marie Bodenant2, Sabrina Debruxelles2, Costanza Rossi2, Régis Bordet2, Denis Vivien2. 1. From Degenerative & Vascular Cognitive Disorders (D.L., C.J., S.M., C.C., T.O., A.-M.M., C.P., H.H., N.D.-P., M.B., C.R., R.B.), Department of Neurology, INSERM U 1171, CHU Lille, Universite Lille; Strokavenir Network (D.L., Y.H., C.J., S.M., I.S., J.-L.M., T.M., M.G., S.S., C.C., E.M.d.B., G.T., T.R., Y.B., O.D., T.O., A.-M.M., P.F., M.Z., A.T.-B., O.O.-W., F.M.M., C.L., A.F., L.L., C.P., M.P., H.H., P.R., N.D.-P., M.B., S.D., C.R., R.B., D.V.), Lille; Inserm UMR-S 919 (Y.H., L.L., D.V.), University Caen-Normandie, GIP Cyceron, Caen; Bordeaux University Hospital (I.S., S.S., M.P., P.R., S.D.), University of Bordeaux; INSERM UMR S894 (J.-L.M., G.T.), Sainte-Anne Hospital, DHU NeuroVasc, Sorbonne Paris Cité, University Paris Descartes; Besançon University Hospital (T.M., E.M.d.B.), University of Franche-Comté; Dijon Stroke Registry (INSERM and INVS) (M.G., Y.B.), Dijon University Hospital, University of Burgundi; University of Rennes (T.R.); University Grenoble Alpes (O.D.); University Hospital Paris Tenon (P.F.); Sorbonne Paris Citéitbonne, University Hospital Paris St Joseph, University Paris Descartes; Rouen University Hospital (A.T.-B., O.O.-W.); University Hospital of Limoges (F.M.M.); Amiens University Hospital (C.L.); and Ste.-Anne Military Teaching Hospital (A.F.), Toulon, France. didier.leys@univ-lille2.fr. 2. From Degenerative & Vascular Cognitive Disorders (D.L., C.J., S.M., C.C., T.O., A.-M.M., C.P., H.H., N.D.-P., M.B., C.R., R.B.), Department of Neurology, INSERM U 1171, CHU Lille, Universite Lille; Strokavenir Network (D.L., Y.H., C.J., S.M., I.S., J.-L.M., T.M., M.G., S.S., C.C., E.M.d.B., G.T., T.R., Y.B., O.D., T.O., A.-M.M., P.F., M.Z., A.T.-B., O.O.-W., F.M.M., C.L., A.F., L.L., C.P., M.P., H.H., P.R., N.D.-P., M.B., S.D., C.R., R.B., D.V.), Lille; Inserm UMR-S 919 (Y.H., L.L., D.V.), University Caen-Normandie, GIP Cyceron, Caen; Bordeaux University Hospital (I.S., S.S., M.P., P.R., S.D.), University of Bordeaux; INSERM UMR S894 (J.-L.M., G.T.), Sainte-Anne Hospital, DHU NeuroVasc, Sorbonne Paris Cité, University Paris Descartes; Besançon University Hospital (T.M., E.M.d.B.), University of Franche-Comté; Dijon Stroke Registry (INSERM and INVS) (M.G., Y.B.), Dijon University Hospital, University of Burgundi; University of Rennes (T.R.); University Grenoble Alpes (O.D.); University Hospital Paris Tenon (P.F.); Sorbonne Paris Citéitbonne, University Hospital Paris St Joseph, University Paris Descartes; Rouen University Hospital (A.T.-B., O.O.-W.); University Hospital of Limoges (F.M.M.); Amiens University Hospital (C.L.); and Ste.-Anne Military Teaching Hospital (A.F.), Toulon, France.
Abstract
OBJECTIVE: To determine whether the ratio single chain (sc)/(sc + 2 chain [tc]) recombinant tissue plasminogen activator (rtPA) influences outcomes in patients with cerebral ischemia. METHODS: We prospectively included consecutive patients treated with IV rtPA for cerebral ischemia in 13 stroke centers and determined the sc/(sc + tc) ratio in the treatment administered to each patient. We evaluated the outcome with the modified Rankin Scale (mRS) at 3 months (prespecified analysis) and occurrence of epileptic seizures (post hoc analysis). We registered Outcome of Patients Treated by IV Rt-PA for Cerebral Ischaemia According to the Ratio Sc-tPA/Tc-tPA (OPHELIE) under ClinicalTrials.gov identifier no. NCT01614080. RESULTS: We recruited 1,004 patients (515 men, median age 75 years, median onset-to-needle time 170 minutes, median NIH Stroke Scale score 10). We found no statistical association between sc/(sc + tc) ratios and handicap (mRS > 1), dependency (mRS > 2), or death at 3 months. Patients with symptomatic intracerebral hemorrhages had lower ratios (median 69% vs 72%, adjusted p = 0.003). The sc/(sc + tc) rtPA ratio did not differ between patients with and without seizures, but patients with early seizures were more likely to have received a sc/(sc + tc) rtPA ratio >80.5% (odds ratio 3.61; 95% confidence interval 1.26-10.34). CONCLUSIONS: The sc/(sc + tc) rtPA ratio does not influence outcomes in patients with cerebral ischemia. The capacity of rtPA to modulate NMDA receptor signaling might be associated with early seizures, but we observed this effect only in patients with a ratio of sc/(sc + tc) rtPA >80.5% in a post hoc analysis.
OBJECTIVE: To determine whether the ratio single chain (sc)/(sc + 2 chain [tc]) recombinant tissue plasminogen activator (rtPA) influences outcomes in patients with cerebral ischemia. METHODS: We prospectively included consecutive patients treated with IV rtPA for cerebral ischemia in 13 stroke centers and determined the sc/(sc + tc) ratio in the treatment administered to each patient. We evaluated the outcome with the modified Rankin Scale (mRS) at 3 months (prespecified analysis) and occurrence of epileptic seizures (post hoc analysis). We registered Outcome of Patients Treated by IV Rt-PA for Cerebral Ischaemia According to the Ratio Sc-tPA/Tc-tPA (OPHELIE) under ClinicalTrials.gov identifier no. NCT01614080. RESULTS: We recruited 1,004 patients (515 men, median age 75 years, median onset-to-needle time 170 minutes, median NIH Stroke Scale score 10). We found no statistical association between sc/(sc + tc) ratios and handicap (mRS > 1), dependency (mRS > 2), or death at 3 months. Patients with symptomatic intracerebral hemorrhages had lower ratios (median 69% vs 72%, adjusted p = 0.003). The sc/(sc + tc) rtPA ratio did not differ between patients with and without seizures, but patients with early seizures were more likely to have received a sc/(sc + tc) rtPA ratio >80.5% (odds ratio 3.61; 95% confidence interval 1.26-10.34). CONCLUSIONS: The sc/(sc + tc) rtPA ratio does not influence outcomes in patients with cerebral ischemia. The capacity of rtPA to modulate NMDA receptor signaling might be associated with early seizures, but we observed this effect only in patients with a ratio of sc/(sc + tc) rtPA >80.5% in a post hoc analysis.
Authors: Ramón Iglesias-Rey; Manuel Rodríguez-Yáñez; Emilio Rodríguez-Castro; José Manuel Pumar; Susana Arias; María Santamaría; Iria López-Dequidt; Pablo Hervella; Clara Correa-Paz; Tomás Sobrino; Denis Vivien; Francisco Campos; Mar Castellanos; José Castillo Journal: Transl Stroke Res Date: 2017-11-07 Impact factor: 6.829