TY - JOUR
T1 - Safety and efficacy of intravenous thrombolysis in stroke patients on prior antiplatelet therapy in the WAKE-UP trial
AU - on behalf of the WAKE-UP investigators
AU - Frey, Benedikt M.
AU - Boutitie, Florent
AU - Cheng, Bastian
AU - Cho, Tae Hee
AU - Ebinger, Martin
AU - Endres, Matthias
AU - Fiebach, Jochen B.
AU - Fiehler, Jens
AU - Ford, Ian
AU - Galinovic, Ivana
AU - Königsberg, Alina
AU - Puig, Josep
AU - Roy, Pascal
AU - Wouters, Anke
AU - Magnus, Tim
AU - Thijs, Vincent
AU - Lemmens, Robin
AU - Muir, Keith W.
AU - Nighoghossian, Norbert
AU - Pedraza, Salvador
AU - Simonsen, Claus Z.
AU - Gerloff, Christian
AU - Thomalla, Götz
AU - Golsari, Amir
AU - Alegiani, Anna
AU - Beck, Christoph
AU - Choe, Chi un
AU - Voget, Dieke
AU - Hoppe, Julia
AU - Schröder, Julian
AU - Häusler, Karl Georg
AU - Rozanski, Michal
AU - Nave, Alexander H.
AU - Wollboldt, Christian
AU - van Sloten, Isabelle
AU - Göhler, Jos
AU - Herm, Juliane
AU - Jungehülsing, Jan
AU - Lückl, Janos
AU - Kröber, Jan M.
AU - Schurig, Johannes
AU - Koehler, Luzie
AU - Schlemm, Ludwig
AU - Knops, Michael
AU - Roennefarth, Maria
AU - Ipsen, Nils
AU - Harmel, Peter
AU - Bathe-Peters, Rouven
AU - Fleischmann, Robert
AU - Held, Valentin
N1 - Publisher Copyright:
© 2020, The Author(s).
PY - 2020/12
Y1 - 2020/12
N2 - Background: One quarter to one third of patients eligible for systemic thrombolysis are on antiplatelet therapy at presentation. In this study, we aimed to assess the safety and efficacy of intravenous thrombolysis in stroke patients on prescribed antiplatelet therapy in the WAKE-UP trial. Methods: WAKE-UP was a multicenter, randomized, double-blind, placebo-controlled clinical trial to study the efficacy and safety of MRI-guided intravenous thrombolysis with alteplase in patients with an acute stroke of unknown onset time. The medication history of all patients randomized in the WAKE-UP trial was documented. The primary safety outcome was any sign of hemorrhagic transformation on follow-up MRI. The primary efficacy outcome was favorable functional outcome defined by a score of 0–1 on the modified Rankin scale at 90 days after stroke, adjusted for age and baseline stroke severity. Logistic regression models were fitted to study the association of prior antiplatelet treatment with outcome and treatment effect of intravenous alteplase. Results: Of 503 randomized patients, 164 (32.6%) were on antiplatelet treatment. Patients on antiplatelet treatment were older (70.3 vs. 62.8 years, p < 0.001), and more frequently had a history of hypertension, atrial fibrillation, diabetes, hypercholesterolemia, and previous stroke or transient ischaemic attack. Rates of symptomatic intracranial hemorrhage and hemorrhagic transformation on follow-up imaging did not differ between patients with and without antiplatelet treatment. Patients on prior antiplatelet treatment were less likely to achieve a favorable outcome (37.3% vs. 52.6%, p = 0.014), but there was no interaction of prior antiplatelet treatment with intravenous alteplase concerning favorable outcome (p = 0.355). Intravenous alteplase was associated with higher rates of favorable outcome in patients on prior antiplatelet treatment with an adjusted odds ratio of 2.106 (95% CI 1.047–4.236). Conclusions: Treatment benefit of intravenous alteplase and rates of post-treatment hemorrhagic transformation were not modified by prior antiplatelet intake among MRI-selected patients with unknown onset stroke. Worse functional outcome in patients on antiplatelets may result from a higher load of cardiovascular co-morbidities in these patients.
AB - Background: One quarter to one third of patients eligible for systemic thrombolysis are on antiplatelet therapy at presentation. In this study, we aimed to assess the safety and efficacy of intravenous thrombolysis in stroke patients on prescribed antiplatelet therapy in the WAKE-UP trial. Methods: WAKE-UP was a multicenter, randomized, double-blind, placebo-controlled clinical trial to study the efficacy and safety of MRI-guided intravenous thrombolysis with alteplase in patients with an acute stroke of unknown onset time. The medication history of all patients randomized in the WAKE-UP trial was documented. The primary safety outcome was any sign of hemorrhagic transformation on follow-up MRI. The primary efficacy outcome was favorable functional outcome defined by a score of 0–1 on the modified Rankin scale at 90 days after stroke, adjusted for age and baseline stroke severity. Logistic regression models were fitted to study the association of prior antiplatelet treatment with outcome and treatment effect of intravenous alteplase. Results: Of 503 randomized patients, 164 (32.6%) were on antiplatelet treatment. Patients on antiplatelet treatment were older (70.3 vs. 62.8 years, p < 0.001), and more frequently had a history of hypertension, atrial fibrillation, diabetes, hypercholesterolemia, and previous stroke or transient ischaemic attack. Rates of symptomatic intracranial hemorrhage and hemorrhagic transformation on follow-up imaging did not differ between patients with and without antiplatelet treatment. Patients on prior antiplatelet treatment were less likely to achieve a favorable outcome (37.3% vs. 52.6%, p = 0.014), but there was no interaction of prior antiplatelet treatment with intravenous alteplase concerning favorable outcome (p = 0.355). Intravenous alteplase was associated with higher rates of favorable outcome in patients on prior antiplatelet treatment with an adjusted odds ratio of 2.106 (95% CI 1.047–4.236). Conclusions: Treatment benefit of intravenous alteplase and rates of post-treatment hemorrhagic transformation were not modified by prior antiplatelet intake among MRI-selected patients with unknown onset stroke. Worse functional outcome in patients on antiplatelets may result from a higher load of cardiovascular co-morbidities in these patients.
KW - Alteplase
KW - Antiplatelet
KW - Aspirin
KW - Clopidogrel
KW - Hemorrhagic transformation
KW - Ischemic stroke
KW - Recombinant human tissue plasminogen activator
KW - Rt-PA
KW - Thrombolysis
KW - WAKE UP
UR - http://www.scopus.com/inward/record.url?scp=85123096231&partnerID=8YFLogxK
U2 - 10.1186/s42466-020-00087-9
DO - 10.1186/s42466-020-00087-9
M3 - Article
AN - SCOPUS:85123096231
SN - 2524-3489
VL - 2
JO - Neurological Research and Practice
JF - Neurological Research and Practice
IS - 1
M1 - 40
ER -