Setareh Salehi Omran, 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.

Intravenous tissue-type plasminogen activator (IV tPA) and endovascular stroke treatment (EST) are considered standard-of-care for acute ischemic stroke. However, it is unclear whether there is a benefit to administrating IV tPA before EST in patients with large vessel occlusion who are eligible for both treatments. The need for IV tPA prior to EST has been further questioned by the results of the randomized DIRECT-MT trial, where EST alone was shown to be noninferior to IV tPA followed by EST.

Although IV tPA may improve early recanalization and reperfusion, there is concern for distal thrombus migration prior to EST, which may make the thrombus less accessible for endovascular retrieval. Data is scarce on how often this occurs. To address this issue, Flint et al performed a retrospective chart review of stroke cases in Kaiser Permanente Northern California’s Stroke EXPRESS program and examined the impact of IV tPA before EST on the rate of distal embolization, recanalization, and outcomes. The healthcare system comprises of 21 hospitals, two of which are comprehensive stroke centers, and is managed by a telemedicine program. All patients treated fully within the Kaiser Permanente Northern California system for both IV tPA and EST were included. Primary outcome was distal embolization, and secondary outcomes were angiographic (complete recanalization) and short- and long-term clinical improvements. Multivariable logistic regression was used to determine whether IV tPA with EST was associated with an increased risk of distal embolization compared to EST alone.

The study included 327 patients with acute ischemic stroke secondary to large vessel occlusion, of which 242 (74%) received IV tPA. Various contraindications prevented the remaining 85 patients from receiving IV tPA. There were no differences in demographics, vascular risk factors, initial National Institute of Health Stroke Scale, or imaging-to-groin-puncture time between patients who did and did not received IV tPA prior to EST. Thirteen patients receiving IV tPA (5.4%) experienced improvement in symptoms and did not undergo subsequent catheter angiogram for EST. Among the 314 patients who had both CT angiography and a subsequent catheter angiogram, distal embolization occurred in 63 cases (20.1%). More than half of the cases of distal embolization occurred by up to two arterial segments. Distal embolization occurred more often in patients who received IV tPA before EST (24.9% versus 7.1% in EST alone). Multivariable logistic regression demonstrated an association between IV tPA use and distal embolization, with an Odds Ratio of 4.69 (95% CI, 1.92 – 11.44; P<0.001). EST could not be attempted in 41.3% of IV tPA treated cases due to distal embolization. The rate of complete recanalization with EST was significantly lower when distal embolization occurred. Complete recanalization was associated with in-hospital improvement in NIH Stroke Scale by 4 or more points, and IV tPA administration and complete recanalization were associated with good functional outcome at 90 days. Among patients who received IV tPA, complete recanalization was associated with good outcome.

The study has several important limitations. Most notably, the retrospective nature of the study lends itself to a selection bias that may have resulted in certain patients not receiving IV tPA before EST. This, along with possible unmeasurable confounders, may have impacted the difference in rate of distal embolization between the two groups. Second, the authors did not analyze whether distal embolization affects acute and long-term clinical improvement (hospital improvement in NIH Stroke Scale by 4 or more points, or good functional outcome at 90 days). Given that distal embolization was associated with lower rate of complete recanalization, it is assumed that these cases also had worse clinical outcome. Third, around 5% of patients receiving IV tPA clinically improved enough to not require EST and were, therefore, not included within the analysis. Given their presumed recanalization, it would be interesting to see whether including these patients within the analysis would have impacted the results. Fourth, the authors do no mention difference in recanalization rates between patients who did and did not receive IV tPA before EST.

Nevertheless, the authors demonstrated that IV tPA before EST is associated with a significant increase in risk of distal embolization, which may make the clot inaccessible for EST. Despite this risk, IV tPA use provides benefit and improved long-term functional outcome. Additionally, significant clinical improvement before EST was seen only among patients receiving IV tPA before EST. These findings emphasize the role of distal embolization after IV tPA and add further information to the role of IV tPA use prior to EST in acute ischemic stroke from large vessel occlusion.