Abstract WP71: Recanalization Leads To Early Clinical Improvement In Patients Treated With Argatroban And Intravenous TPA A Subanalysis Of The Argatroban Tpa Stroke Study
Background and Objectives: Early neurological improvement (ENI) at 2-hours post thrombolysis has recently been proposed to most accurately predict recanalization when repeat vascular imaging is not available. However, these studies analyzed recanalization at a delayed time point (≥24 hours). The Argatroban tPA Stroke Study (ARTSS-1), is a recently completed NIH sponsored, Phase IIa, prospective, open-label, safety and activity study of Argatroban and rtPA in patients with ischemic stroke (NCT00268762). We hypothesized 2-hour recanalization correlates with ENI (NIHSS improvement of 20% or greater from baseline).
Methods: A total of 65 patients with intracranial large vessel occlusive disease were given standard dose (0.9mg/kg) tPA and a 100 μg/kg bolus of argatroban followed by infusion of 1 μg/kg per minute for 48 hours adjusted to a PTT of 1.75 times baseline. Pre-tPA vessel imaging using TCD or CTA confirmed intracranial occlusions. A multivariate logistic regression tested whether recanalization at 2 hours was associated with ENI after controlling for age, NIHSS, clot location (ICA, MCA or vertebrobasilar). We analyzed whether patients with ENI had statistically significant greater odds of an excellent mRS (0 or 1) at day 7.
Results: Recanalization data was available for 47 patients at 2-hours. ENI occurred at 2-hours in 46% patients. Patients with any recanalization (complete or partial) at 2-hours were more likely to experience ENI (OR 3.4; 95% CI 0.71-16.6, p=0.124). This association strengthened when 2-hour complete recanalization was analyzed (OR 5.4; 95% CI 0.98-29.2, p=0.053). In an unadjusted analysis, patients with ENI at 2-hours were five times more likely to have excellent mRS outcomes at day 7 (OR 4.7; 95% CI 1.4-15.6, p=0.01). In the adjusted model, the association remained significant (OR 3.8; 95%CI 1.1-13.4, p=0.041).
Conclusion: Two-hour recanalization is predictive of early neurological improvement and better early clinical outcomes in patients treated with combination Argatroban and tPA. A randomized, controlled clinical trial of this promising adjunctive therapy is warranted and ongoing (ARTSS-2 trial, NCT01464788).
- © 2012 by American Heart Association, Inc.