Low-Versus Standard-Dose Alteplase in Patients on Prior Antiplatelet Therapy The ENCHANTED Trial (Enhanced Control of Hypertension and Thrombolysis Stroke Study)
Journal
Stroke
ISSN
0039-2499
1524-4628
Date Issued
2017
Author(s)
Thompson G. Robinson
Xia Wang
Hisatomi Arima
Philip M. Bath
Laurent Billot
Joseph P. Broderick
Andrew M. Demchuk
Geoffery A. Donnan
Jong S. Kim
Pablo M. Lavados
Tsong-Hai Lee
Richard I. Lindley
Sheila C. O. Martins
VERONICA VIVIANA OLAVARRIA IANISZEWSKY
Jeyaraj D. Pandian
Mark W. Parsons
Octavio M. Pontes-Neto
Stefano Ricci
Shoichiro Sato
Vijay K. Sharma
Thang H. Nguyen
Ji-Guang Wang
Mark Woodward
John Chalmers
Craig S. Anderson
Type
Resource Types::text::journal::journal article
URL Institutional Repository
Abstract
<jats:sec>
<jats:title>Background and Purpose—</jats:title>
<jats:p>Many patients receiving thrombolysis for acute ischemic stroke are on prior antiplatelet therapy (APT), which may increase symptomatic intracerebral hemorrhage risk. In a prespecified subgroup analysis, we report comparative effects of different doses of intravenous alteplase according to prior APT use among participants of the international multicenter ENCHANTED study (Enhanced Control of Hypertension and Thrombolysis Stroke Study).</jats:p>
</jats:sec>
<jats:sec>
<jats:title>Methods—</jats:title>
<jats:p>Among 3285 alteplase-treated patients (mean age, 66.6 years; 38% women) randomly assigned to low-dose (0.6 mg/kg) or standard-dose (0.9 mg/kg) intravenous alteplase within 4.5 hours of symptom onset, 752 (22.9%) reported prior APT use. Primary outcome at 90 days was the combined end point of death or disability (modified Rankin Scale [mRS] scores, 2–6). Other outcomes included mRS scores 3 to 6, ordinal mRS shift, and symptomatic intracerebral hemorrhage by various standard criteria.</jats:p>
</jats:sec>
<jats:sec>
<jats:title>Results—</jats:title>
<jats:p>
There were no significant differences in outcome between patients with and without prior APT after adjustment for baseline characteristics and management factors during the first week; defined by mRS scores 2 to 6 (adjusted odds ratio [OR], 1.01; 95% confidence interval [CI], 0.81–1.26;
<jats:italic>P</jats:italic>
=0.953), 3 to 6 (OR, 0.95; 95% CI, 0.75–1.20;
<jats:italic>P</jats:italic>
=0.662), or ordinal mRS shift (OR, 1.03; 95% CI, 0.87–1.21;
<jats:italic>P</jats:italic>
=0.770). Alteplase-treated patients on prior APT had higher symptomatic intracerebral hemorrhage (OR, 1.82; 95% CI, 1.00–3.30;
<jats:italic>P</jats:italic>
=0.051) according to the safe implementation of thrombolysis in stroke-monitoring study definition. Although not significant (
<jats:italic>P</jats:italic>
-trend, 0.053), low-dose alteplase tended to have better outcomes than standard-dose alteplase in those on prior APT compared with those not using APT (mRS scores of 2–6; OR, 0.84; 95% CI, 0.62–1.12 versus OR, 1.16; 95% CI, 0.99–1.36).
</jats:p>
</jats:sec>
<jats:sec>
<jats:title>Conclusions—</jats:title>
<jats:p>Low-dose alteplase may improve outcomes in thrombolysis-treated acute ischemic stroke patients on prior APT, but this requires further evaluation in a randomized controlled trial.</jats:p>
</jats:sec>
<jats:sec>
<jats:title>Clinical Trial Registration—</jats:title>
<jats:p>
URL:
<jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="http://www.clinicaltrials.gov">http://www.clinicaltrials.gov</jats:ext-link>
. Unique identifier: NCT01422616.
</jats:p>
</jats:sec>
<jats:title>Background and Purpose—</jats:title>
<jats:p>Many patients receiving thrombolysis for acute ischemic stroke are on prior antiplatelet therapy (APT), which may increase symptomatic intracerebral hemorrhage risk. In a prespecified subgroup analysis, we report comparative effects of different doses of intravenous alteplase according to prior APT use among participants of the international multicenter ENCHANTED study (Enhanced Control of Hypertension and Thrombolysis Stroke Study).</jats:p>
</jats:sec>
<jats:sec>
<jats:title>Methods—</jats:title>
<jats:p>Among 3285 alteplase-treated patients (mean age, 66.6 years; 38% women) randomly assigned to low-dose (0.6 mg/kg) or standard-dose (0.9 mg/kg) intravenous alteplase within 4.5 hours of symptom onset, 752 (22.9%) reported prior APT use. Primary outcome at 90 days was the combined end point of death or disability (modified Rankin Scale [mRS] scores, 2–6). Other outcomes included mRS scores 3 to 6, ordinal mRS shift, and symptomatic intracerebral hemorrhage by various standard criteria.</jats:p>
</jats:sec>
<jats:sec>
<jats:title>Results—</jats:title>
<jats:p>
There were no significant differences in outcome between patients with and without prior APT after adjustment for baseline characteristics and management factors during the first week; defined by mRS scores 2 to 6 (adjusted odds ratio [OR], 1.01; 95% confidence interval [CI], 0.81–1.26;
<jats:italic>P</jats:italic>
=0.953), 3 to 6 (OR, 0.95; 95% CI, 0.75–1.20;
<jats:italic>P</jats:italic>
=0.662), or ordinal mRS shift (OR, 1.03; 95% CI, 0.87–1.21;
<jats:italic>P</jats:italic>
=0.770). Alteplase-treated patients on prior APT had higher symptomatic intracerebral hemorrhage (OR, 1.82; 95% CI, 1.00–3.30;
<jats:italic>P</jats:italic>
=0.051) according to the safe implementation of thrombolysis in stroke-monitoring study definition. Although not significant (
<jats:italic>P</jats:italic>
-trend, 0.053), low-dose alteplase tended to have better outcomes than standard-dose alteplase in those on prior APT compared with those not using APT (mRS scores of 2–6; OR, 0.84; 95% CI, 0.62–1.12 versus OR, 1.16; 95% CI, 0.99–1.36).
</jats:p>
</jats:sec>
<jats:sec>
<jats:title>Conclusions—</jats:title>
<jats:p>Low-dose alteplase may improve outcomes in thrombolysis-treated acute ischemic stroke patients on prior APT, but this requires further evaluation in a randomized controlled trial.</jats:p>
</jats:sec>
<jats:sec>
<jats:title>Clinical Trial Registration—</jats:title>
<jats:p>
URL:
<jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="http://www.clinicaltrials.gov">http://www.clinicaltrials.gov</jats:ext-link>
. Unique identifier: NCT01422616.
</jats:p>
</jats:sec>
Subjects
aspirin
;
brain infarction
;
hypertension
;
intracranial hemorrhages
;
tissue plasminogen activator