Functional Outcome of Intravenous Thrombolysis in Patients With Lacunar Infarcts in the WAKE-UP Trial
JAMA Neurol. 2019-06-01; 76(6): 641
DOI: 10.1001/JAMANEUROL.2019.0351
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1. JAMA Neurol. 2019 Jun 1;76(6):641-649. doi: 10.1001/jamaneurol.2019.0351.
Functional Outcome of Intravenous Thrombolysis in Patients With Lacunar Infarcts
in the WAKE-UP Trial.
Barow E(1), Boutitie F(2)(3)(4), Cheng B(1), Cho TH(5)(6), Ebinger M(7)(8),
Endres M(7)(9), Fiebach JB(7), Fiehler J(10), Ford I(11), Galinovic I(7), Nickel
A(1), Puig J(12), Roy P(2), Wouters A(13)(14)(15), Magnus T(1), Thijs V(16)(17),
Lemmens R(13)(14)(15), Muir KW(18), Nighoghossian N(5)(6), Pedraza S(12),
Simonsen CZ(19), Gerloff C(1), Thomalla G(1); WAKE-UP Investigators.
Author information:
(1)Klinik und Poliklinik für Neurologie, Kopf- und Neurozentrum, University
Medical Center Hamburg-Eppendorf, Hamburg, Germany.
(2)Hospices Civils de Lyon, Service de Biostatistique, Lyon, France.
(3)Université Lyon 1, Villeurbanne, France.
(4)Centre National de la Recherche Scientifique, Unité de Mixte de Recherche
5558, Laboratoire de Biométrie et Biologie Evolutive, Equipe
Biostatistique-Santé, Villeurbanne, France.
(5)Department of Stroke Medicine, Université Claude Bernard Lyon 1, CREATIS
Centre National de la Recherche Scientifique Unité de Mixte de Recherche 5220,
Institut National de la Santé et de la Recherche Médicale U1206, Institut
National des Sciences Appliquées-Lyon, Lyon, France.
(6)Hospices Civils de Lyon, Lyon, France.
(7)Centrum für Schlaganfallforschung Berlin, Charité-Universitätsmedizin Berlin,
Berlin, Germany.
(8)Neurologie der Rehaklinik Medical Park Humboldtmühle, Berlin, Germany.
(9)Klinik und Hochschulambulanz für Neurologie, Charité-Universitätsmedizin
Berlin, Berlin, Germany.
(10)Department of Diagnostic and Interventional Neuroradiology, University
Medical Center Hamburg-Eppendorf, Hamburg, Germany.
(11)Robertson Centre for Biostatistics, University of Glasgow, Glasgow, United
Kingdom.
(12)Department of Radiology, Institut de Diagnostic per la Image, Hospital Dr
Josep Trueta, Institut d’Investigació Biomèdica de Girona, Salt, Girona, Spain.
(13)Department of Neurology, University Hospitals Leuven, Leuven, Belgium.
(14)Department of Neurosciences, Experimental Neurology, Katholieke Universiteit
Leuven, Leuven, Belgium.
(15)Vlaams Instituut voor Biotechnologie, Center for Brain & Disease Research,
Laboratory of Neurobiology, Leuven, Belgium.
(16)Florey Institute of Neuroscience and Mental Health, University of Melbourne,
Parkville, Victoria, Australia.
(17)Department of Neurology, Austin Health, Heidelberg, Victoria, Australia.
(18)Institute of Neuroscience & Psychology, University of Glasgow, Glasgow,
United Kingdom.
(19)Department of Neurology, Aarhus University Hospital, Aarhus, Denmark.
Comment in
JAMA Neurol. 2019 Jun 1;76(6):637-638.
Importance: The rationale for intravenous thrombolysis in patients with lacunar
infarcts is debated, since it is hypothesized that the microvascular occlusion
underlying lacunar infarcts might not be susceptible to pharmacological
reperfusion treatment.
Objective: To study the efficacy and safety of intravenous thrombolysis among
patients with lacunar infarcts.
Design, Setting, and Participants: This exploratory secondary post hoc analysis
of the WAKE-UP trial included patients who were screened and enrolled between
September 2012 and June 2017 (with final follow-up in September 2017). The
WAKE-UP trial was a multicenter, double-blind, placebo-controlled randomized
clinical trial to study the efficacy and safety of intravenous thrombolysis with
alteplase in patients with an acute stroke of unknown onset time, guided by
magnetic resonance imaging. All 503 patients randomized in the WAKE-UP trial were
reviewed for lacunar infarcts. Diagnosis of lacunar infarcts was based on
magnetic resonance imaging and made by consensus of 2 independent investigators
blinded to clinical information.
Main Outcomes and Measures: The primary efficacy variable was favorable outcome
defined by a score of 0 to 1 on the modified Rankin Scale at 90 days after
stroke, adjusted for age and severity of symptoms.
Results: Of the 503 patients randomized in the WAKE-UP trial, 108 patients
(including 74 men [68.5%]) had imaging-defined lacunar infarcts, whereas 395
patients (including 251 men [63.5%]) had nonlacunar infarcts. Patients with
lacunar infarcts were younger than patients with nonlacunar infarcts (mean age
[SD], 63 [12] years vs 66 [12] years; P = .003). Of patients with lacunar
infarcts, 55 (50.9%) were assigned to treatment with alteplase and 53 (49.1%) to
receive placebo. Treatment with alteplase was associated with higher odds of
favorable outcome, with no heterogeneity of treatment outcome between lacunar and
nonlacunar stroke subtypes. In patients with lacunar strokes, a favorable outcome
was observed in 31 of 53 patients (59%) in the alteplase group compared with 24
of 52 patients (46%) in the placebo group (adjusted odds ratio [aOR], 1.67 [95%
CI, 0.77-3.64]). There was 1 death and 1 symptomatic intracranial hemorrhage
according to Safe Implementation of Thrombolysis in Stroke-Monitoring Study
criteria in the alteplase group, while no death and no symptomatic intracranial
hemorrhage occurred in the placebo group. The distribution of the modified Rankin
Scale scores 90 days after stroke also showed a nonsignificant shift toward
better outcomes in patients with lacunar infarcts treated with alteplase, with an
adjusted common odds ratio of 1.94 (95% CI, 0.95-3.93).
Conclusions and Relevance: While the WAKE-UP trial was not powered to demonstrate
the efficacy of treatment in subgroups of patients, the results indicate that the
association of intravenous alteplase with functional outcome does not differ in
patients with imaging-defined lacunar infarcts compared with those experiencing
other stroke subtypes.
DOI: 10.1001/jamaneurol.2019.0351
PMCID: PMC6563546
PMID: 30907934 [Indexed for MEDLINE]