Low- versus standard-dose alteplase in patients on prior antiplatelet therapy: The ENCHANTED Trial (Enhanced Control of Hypertension and Thrombolysis Stroke Study).

Journal article

Background and Purpose

Many patients receiving thrombolysis for acute ischemic stroke (AIS) are on prior antiplatelet therapy (APT), which may increase symptomatic intracerebral hemorrhage (sICH) risk. In a pre-specified subgroup analysis, we report comparative effects of different doses of intravenous (iv) alteplase according to prior APT use among participants of the international multi-center ENhanced Control of Hypertension And Thrombolysis strokE stuDy.

Methods

Among 3285 alteplase-treated patients (mean age 66.6 years, 38% female) randomly assigned to low-dose (0.6mg/kg) or standard-dose (0.9mg/kg) iv alteplase within 4.5 hours of symptom onset, 752 (22.9%) reported prior APT use. Primary outcome at 90-days was the combined endpoint of death or disability (modified Rankin scale [mRS] scores 2-6). Other outcomes included mRS scores 3-6, ordinal mRS shift, and sICH by various standard criteria.

Results

There were no significant differences in outcome between patients with and without prior APT after adjustment for baseline characteristics and management factors over the first week; defined by mRS scores 2-6 (adjusted odds ratio 1.01, 95% confidence interval [CI] 0.81-1.26; p=0.953), 3-6 (0.95 [0.75-1.20]; p=0.662) or ordinal mRS shift (1.03 [0.87-1.21]; p=0.770). Alteplase-treated patients on prior APT had higher sICH (1.82 [1.00-3.30]; p=0.051) according to the Safe Implementation of Thrombolysis in Stroke-Monitoring Study definition. Although not significant (p trend 0.053), low-dose alteplase tended to have better outcomes than standard-dose in those on prior APT compared to those not using APT (mRS scores of 2-6, 0.84 [0.62-1.12] vs. 1.16 [0.99-1.36]).

Conclusions

Low-dose alteplase may improve outcomes in thrombolysis-treated AIS patients on prior APT, but this requires further evaluation in a randomized controlled trial.

Authors: Robinson, T; Wang, X; Arima, H; Bath, P; Billot, L

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: American Heart Association
• Journal: Stroke
• Volume: 48
• Issue: 7
• Pages: 1877-1883
• Publication date: 2017-06-01
• Acceptance date: 2017-03-13
• DOI: 10.1161/STROKEAHA.116.016274
• EISSN: 1524-4628
• ISSN: 0039-2499
• Language: English
• Keywords: hypertension; aspirin; tissue plasminogen activator; intracranial hemorrhages; brain infarction