Abstract WP58: Early Recanalization Rates Do Not Differ among Stroke Subtypes when treated with Argatroban and intravenous tPA: a Subanalysis of the Argatroban TPA Stroke Study

Background and Objectives: Argatroban is a direct thrombin inhibitor that safely augments the benefit of tPA in animal stroke models. The Argatroban tPA Stroke Study (ARTSS-1), was a recently completed NIH sponsored, Phase IIa, prospective, open-label, safety and activity study of Argatroban and tPA in patients with ischemic stroke ( NCT00268762 ). Symptomatic hemorrhage occurred in 4.6% and rates of complete recanalization were 30% and 63% at 2 and 24 hours, respectively. We hypothesized that stroke subtypes might respond differently to the treatment combination. 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 was performed to test whether stroke subtype independently influenced recanalization after controlling for: NIHSS, antithrombotic use, diabetes, age and clot location (ICA, MCA, Vertebrobasilar). Results: Recanalization data was available for 47 patients at 2-hours. Baseline characteristics are displayed in the table. After adjusting for age, NIHSS, diabetes, clot location and previous antithrombotic use, there was no difference between any recanalization at 2-hours in the different stroke etiologies. Interestingly, M1 clots were more likely to recanalize compared with M2 (OR 6.2; 95% CI 1.3-25, p=0.019). Results were similar when only analyzing 2-hours complete recanalization. Conclusion: Although all large vessel stroke subtypes recanalize at similar rates when treated with combination Argatroban and rtPA, larger thrombi may benefit to a greater degree. A randomized, controlled clinical trial of this promising adjunctive therapy is warranted and ongoing (ARTSS-2 trial, NCT01464788 ).