Kaustubh Limaye, MD

Gautheron V, Xie Y, Tisserand M, Raoult H, Soize S, Naggara O, et al. Outcome After Reperfusion Therapies in Patients With Large Baseline Diffusion-Weighted Imaging Stroke Lesions: A THRACE Trial (Mechanical Thrombectomy After Intravenous Alteplase Versus Alteplase Alone After Stroke) Subgroup Analysis. Stroke. 2018

The treatment landscape of acute ischemic stroke secondary to large vessel occlusion changed significantly in 2015 with the publication of 5 clinical trials that compared intravenous alteplase (IV t-pA) with IV t-pA and intra-arterial therapy (IAT). These clinical trials showed unequivocal benefit in reducing morbidity with the ESCAPE trial even showing mortality benefit. A similar trial conducted at 26 centers in France, THRACE (mechanical thrombectomy after intravenous alteplase versus alteplase alone after stroke) randomized 414 acute stroke patients with large vessel occlusion in either arm (IV t-PA vs IV tPA + IAT). 42 % of patients (IV tPA alone) vs. 53% (IV tPA +IAT) achieved functional independence [OR-1.55,95%CI 1.05-2.30; p-0.028], supporting data from the previous clinical trials. As this study was designed before the results of the IMS-III were published, it included patients treated within 4 hours of symptom onset. Other inclusion criteria were age 18-80 years, NIHSS 10-25, both anterior and posterior circulation and initiation of IAT within 5 hours.

In this subgroup analysis, the investigators have looked at large baseline core patients and their outcomes. A total of 56 patients were treated who had large baseline core (>70 ml), out of which 3 patients were lost to follow up. Out of the 53 patients, 12 patients had a good outcome (mRS<2), and 5/12 were left hemispheric strokes with a median DWI-ASPECTS of 4.5. Notable was that all 12/37 who achieved favorable outcome had an intracranial M1 occlusion and none of the 16 ICA T/L occlusions. 5/12 of these patients were treated with thrombolysis and thrombectomy, with 2/4 achieving TICI 2b-3 reperfusion; none had any 24-hour hemorrhage. In the patients with a core >100 ml, 8/37 patients had a favorable outcome.

Medical comorbidities like atherosclerosis and history of smoking were more frequent in patients with poor outcome. In addition, the involvement of deep MCA territory was associated with poor outcomes, again highlighting the “physiologic” role of ASPECTS as compared to volume alone in predicting recovery also in predicting hemorrhagic transformation.

There are a few limitations in this study, like lack of reperfusion data on patients not treated with thrombectomy and DWI lesion estimation at symptom onset to median of 111 minutes — which may lead to difference in stratification of this patient population considering lesion reversibility post intravenous thrombolysis. This study points towards a few indicators of improvement in this population, like 12/37 patients with M1 occlusion had favorable outcome as opposed to 0/16 with ICA T/L occlusion and all 8 patients included in this study > 75 years had a final mRS>2 at 3 months. Also, the favorable outcomes of patients with core > 70 ml vs. >100 ml was similar, highlighting the most important fact that large core does not essentially ≠ bad outcome. Randomized clinical controlled trials that assess the treatment benefit of IAT in patients with large core at presentation are the need of the hour!