Manya Khrlobyan, DO, MS

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.

Among patients presenting with a large vessel occlusion (LVO), the standard of care is administering IV tPA prior to endovascular therapy, but this practice has recently come under question. With the recanalization rate of large vessel occlusion in acute ischemic stroke being less than 20% with IV tPA alone, many are questioning if proceeding straight to endovascular intervention makes more sense. One of the arguments against administering IV tPA is the risk of distal embolization rendering a once accessible clot inaccessible for mechanical thrombectomy.

This study retrospectively collected data from a large integrated stroke telemedicine program to examine the impact of IV tPA administration prior to endovascular therapy (EVT) on the rate of distal embolization and rate of target recanalization, and it assessed both the short- and long-term clinical outcomes using NIHSS and mRS, respectively.

Between October 2015 and April 2018, 327 patients with LVO acute ischemic stroke were sent for EVT. 242 (74%) received IV t-PA, and 85 (26%) did not receive IV tPA because they did not meet eligibility criteria. Of the patients who received IV tPA, 13/242 (5.4%) improved significantly enough that the treating physician did not recommend endovascular intervention. Distal embolization was seen in 20.1% of cases, but the majority, 79.3%, showed no change in clot location between CTA and subsequent angiogram. Those who received IV tPA had a higher rate of distal embolization (57/229, 24.9%) than those that did not (6/85, 7.1%). Of the distal embolization cases, 26/63 (41.3%) could not have attempted EVT because of clot location compared to only 8/249 (3.2%) in those without distal embolization (p<0.001). Of note, 54.2% of distal embolizations were beyond the proximal M2 segment, and 23.8% were to an M3 segment or beyond.

In terms of clinical outcomes, they found that in the subgroup of patients with mTICI 2b/3 recanalization after EVT, prior IV tPA administration was not associated with in-hospital improvement in NIHSS, but among patients with mTICI 2b/3 recanalization after EVT, prior tPA administration was associated with good outcome at 90 days (69/163, 42.3% vs 18/66, 27.3%; p=0.04).

IV tPA administration prior to EVT may represent a double-edged sword. While IV tPA may lead to softening of the thrombus and thereby facilitate easier mechanical thrombectomy with fewer required passes, it may also lead to distal embolization and render a clot inaccessible for mechanical thrombectomy. Keeping in mind the limitations of this being a retrospective study, it did find the rate of distal embolization was higher in those treated with IV tPA, which, in turn, reduced the number of attempted mechanical thrombectomies. Despite the increased distal embolization rate, IV tPA was associated with improved long-term clinical outcomes. Prior to considering any change in current standard of care management for LVO and acute ischemic stroke, multicenter randomized controlled trials are needed to assess the risks, benefits, and clinical outcomes in patients with LVO treated with IV tPA before MT vs direct MT.