Background and Objectives: A randomized trial of IV-tPA + thrombin-inhibition with argatroban in non-endovascular stroke patients (ARTSS-2) recently demonstrated safety and signal of efficacy compared to tPA alone. The current study, ARTSS-IA, intended to study the safety and feasibility among concurrent IV-tPA, high-dose argatroban and endovascular therapy (ET) in large vessel occlusion.
Methods: Eligible patients received IV-tPA (0.9mg/kg) and had CT-angiogram-proven intracranial large vessel occlusions requiring <6-hours ET. During IV-tPA, a 100 μg/kg argatroban bolus was followed by 12-hour infusion to target an aPTT 2.25 times baseline. Feasibility, defined as ability to combine treatments without ET delays, was compared to data from consecutive tPA+ET treatments. Safety was incidence of symptomatic intracerebral hemorrhage (sICH).
Results: Between 6/15 and 5/16, all pre-planned 10 patients were enrolled: median age=68.5 (IQR 12-24; range 52-92), median NIHSS=19.5 (range 6-25) and 70% male. Occlusions were proximal MCA (n=6), terminal ICA (n=1) and proximal PCA (n=1). All patients began argatroban before ET and completed 12-hour infusions. Study patients experienced trivial or no time delays in metrics (i.e., imaging to groin-puncture, groin-to-clot, etc) compared to non-ARTSS-IA patients during the same time (figure). Embolectomy with stentreivers were performed in all but 1 patient, a proximal PCA occlusion deemed too hazardous for device passage. All the remaining 9 patients achieved excellent angiographic reperfusion (TICI ≥2b); with 7 achieving complete reperfusion (TICI=3). There were no sICH, systemic hemorrhages, or ET complications. 24 hour NIHSS scores were markedly lower (median=7, IQR 2-16, range 1-21). At 90-days, 6 (60%) patients were functionally independent (mRS=0-2) and none died.
Conclusion: In patients treated with IV tPA and ET, adjunctive argatroban appears safe and high rates of reperfusion warrant further study.