Walter Valesky, MD

Flint AC, Avins AL, Eaton A, Uong S, Cullen SP, Hsu DP, Edwards NJ, Reddy PA, Klingman JG, Rao VA, et al. Risk of Distal Embolization From tPA (Tissue-Type Plasminogen Activator) Administration Prior to Endovascular Stroke Treatment. Stroke. 2020;51:2697-2704.

The authors utilize a unique approach to weigh-in on a brewing controversy in acute ischemic stroke management: Is intravenous thrombolysis (IVT) beneficial in large vessel occlusion (LVO) in patients receiving endovascular therapy (EVT)? Rather than reporting on symptomatic intracranial hemorrhage, as is typical in studies evaluating IVT, these authors evaluated distal migration of clot that was subsequently not amenable to retrieval with EVT in patients treated with and without thrombolytics. The hypothesis being that IVT will reduce clot size to a point that it may be dislodged from a larger, more proximal vessel to embolize into a smaller caliber, more distal vessel and not be amenable to EVT.

For their evaluation, the authors utilized a retrospective record review of patients evaluated at the Kaiser Permanente healthcare system in Northern California undergoing EVT after presenting with symptoms of acute ischemic stroke. EVT was performed at one of two comprehensive stroke centers (CSC) in the area functioning as a receiving hospital for 19 other primary stroke centers (PSC). Patients were included whether they initially presented to the PSC and were transferred or if they presented directly to the CSC. Successful recanalization was defined as a modified thrombolysis in cerebral infarction (mTICI) scale of 2b/3.  

Over 30 months from 2015 to 2018, the authors identified 314 patients who underwent EVT after a computed tomography angiography (CTA) confirming an LVO. Of these, 63 (20.1%) showed distal embolization when comparing the original CTA with findings from the catheter angiogram with distal clot migration. Distal clot migration significantly limited ability to obtain mTICI 2b/3 recanalization compared to individuals with no clot migration, 46% vs 81.7%, respectively. IVT was the only factor associated with significant clot embolization with an odds ratio of 4.69 (95% CI 1.92-11.44).

There were no significant differences between baseline characteristics of those receiving IVT with EVT or EVT alone. Average age was 75 years with approximately three quarters of patients being either white or of Asian descent. The initial National Institutes of Health Stroke Scale score (NIHSS) at hospital presentation was 16 for each group. Anterior circulation strokes accounted for 90% of patients sent for EVT.

Clinical outcomes were assessed by NIHSS improvement of 4 points or greater during hospitalization and modified Rankin score (mRS) at 90 days. Both these outcomes demonstrated significant improvement in those patients receiving IVT prior to thrombectomy compared to those receiving EVT alone. Those receiving IVT and EVT demonstrated ‘good functional outcome’ demonstrated by mRS 0-2 at 90 days in 39.7% of patients vs 22.4% in those receiving EVT and not receiving thrombolytics.

This study attempts to weigh the benefit of immediate recanalization with IVT against the risk of downstream embolization of clot. The retrospective nature of the current study limits the applicability of its findings to hypothesis generation; however, insights may be extrapolated. Seventy-eight percent of those with a distal embolization were located at the mid M2 segment or further, a location that has been previously shown to have poor success with endovascular therapy.1 Based on previous literature demonstrating varied recanalization rates with IVT,2 it is possible that future trials may lead to a strategy of selective thrombolytics for more distal sections of the anterior circulation that are less amenable to stent retrieval. Should we be preserving more proximal occlusions, such as the internal carotid artery and M1 portion of the MCA for an EVT-only strategy to prevent distal embolization in those patients presenting to comprehensive stroke centers in the first 6 hours? These findings follow the publication of the DIRECT-MT trial demonstrating that EVT only was non-inferior to IVT+EVT in a Chinese population.3 However, the reader must be aware that patients transferred from one institution to another for EVT are not adequately described in both this trial and the DIRECT-MT trial, which limits findings in those patients. Future randomized trials will be the only way to clarity and a change in clinical practice.


1.    Goyal M, Menon BK, van Zwam WH, et al. Endovascular thrombectomy after large-vessel ischaemic stroke: a meta-analysis of individual patient data from five randomised trials. The Lancet. 2016;387:1723-1731.

2.    Menon BK, Al-Ajlan FS, Najm M, et al. Association of Clinical, Imaging, and Thrombus Characteristics With Recanalization of Visible Intracranial Occlusion in Patients With Acute Ischemic Stroke. JAMA. 2018;320:1017.

3.    Yang P, Zhang Y, Zhang L, et al. Endovascular Thrombectomy with or without Intravenous Alteplase in Acute Stroke. N Engl J Med. 2020;382:1981-1993.