Proportion of single-chain recombinant tissue plasminogen activator and outcome after stroke.


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 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.

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@article{Leys2016ProportionOS, title={Proportion of single-chain recombinant tissue plasminogen activator and outcome after stroke.}, author={Didier Leys and Yannick Hommet and Cl{\'e}mence Jacquet and Sol{\`e}ne L Y Moulin and Igor Sibon and J-L Mas and Thierry Moulin and Maurice E Giroud and Sharmila Sagnier and Charlotte Cordonnier and Elisabeth Medeiros de Bustos and G Turc and Thomas Ronzi{\`e}re and Yannick B{\'e}jot and O Detante and Thavarak Ouk and Anne-Marie Mendyk and Pascal Favrole and M Zuber and Aude Triquenot-Bagan and Ozlem Ozkul-Wermester and Francisco Macian Montoro and Chantal Lamy and Anthony Faivre and Laurent Lebouvier and Camille Potey and Mathilde Poli and Hilde H{\'e}non and Pauline Renou and Nelly Dequatre-Ponchelle and Marie Bodenant and Sabrina Debruxelles and Costanza Rossi and R{\'e}gis Bordet and Denis Vivien}, journal={Neurology}, year={2016}, volume={87 23}, pages={2416-2426} }