Alteplase With Endovascular Thrombectomy Improves Functional Outcomes, Survival, but With Increased Risk of Symptomatic Intracranial Hemorrhage

Author(s):

Endovascular therapy with alteplase was associated with lower morality, home discharge destination, greater likelihood to have no major disability, and ability to ambulate at discharge.

Eric E. Smith, MD

Results from an observational study showed that the addition of alteplase to endovascular therapy (EVT) improves in-hospital mortality and functional outcomes in patients with acute ischemic stroke; however, there was an increased association with symptomatic intracranial hemorrhage (sICH).¹

In a cohort of 10,548 patients on alteplase and 5284 with only EVT, those with alteplase were less likely to die (11.1% vs 13.9%; adjusted odds ratio [aOR], 0.83; 95% CI, 0.77-0.89; P <.001), more likely to have no major disability based on modified Rankin scale (mRS) score of 2 or less at discharge (28.5% vs 20.7%; aOR, 1.36; 95% CI, 1.28-1.45; P <.001), and to have better reperfusion based on modified Thrombolysis in Cerebral Infarction grade 2b or better (90.9% vs 88.0%; aOR, 1.39; 95% CI, 1.28-1.50; P <.001).

The addition of alteplase was associated with a higher risk of sICH (6.5% vs 5.3%; OR, 1.28; 95% CI, 1.16-1.42; P <.001), although the investigators, including lead author Eric E. Smith, MD, medical director, Cognitive Neurosciences Clinic, University of Calgary, concluded that this "does not translate to worsening in discharge disability or mortality." They added, "alteplase or other thrombolytics may still have an important role in patients undergoing EVT for large vessel occlusion, particularly in patients where a delay in accessing the angiography suite is anticipated, such as when transfer to an EVT-capable site is required or when personnel are off-site."

Conducted between February 2019 and June 2020, the study included participants from the Get With The Guidelines (GWTG)-Stroke registry who had been treated within 6 hours of time last well known. Between the 2 study arms, those who received alteplase with EVT treatment were younger (alteplase: median age, 70 years; IQR, 59.0-81.0; no alteplase: median age, 74 years; IQR, 63.0-83.0), had a lower rate of atrial fibrillation or flutter (24.8% vs 50.9%) prior stroke (5.8% vs 31.8%), and prior heart failure (12.3% vs 18.3%).

Despite the increased rates of sICH, those who received alteplase did not demonstrate higher rates of other life-threatening (1.0% vs 1.1%) or other serious bleeding complications (5.1% vs 4.5%). The addition of alteplase was also associated with home discharge destination (aOR, 1.29; 95% CI, 1.23-1.36; P <.001) and ability to ambulate at discharge (aOR, 1.33; 95% CI, 1.26-1.40; P <.001). The findings across the study remained similar when analyzing only direct-arriving patients, excluding those transferred for EVT, as well as in sensitivity analyses for those who arrived after 3 hours vs those arriving after 4.5 hours.

"To fully define the role of alteplase or other lytics (eg, tenecteplase) in combination with EVT, more data from randomized clinical trials will be needed to narrow the margin of noninferiority or to prove superiority," Smith et al concluded.

In the literature, 6 randomized trials have compared EVT with alteplase with EVT without alteplase, finding small differences without evidence for the superiority of either approach. A recent meta-analysis of all the studies showed that EVT without alteplase resulted in worse disability outcomes at 90 days, but this difference was not statistically significant.² Using this data, the European Stroke Organization-European Society for Minimally Invasive Neurological Therapy recommended, based on moderate-quality evidence, that alteplase continue to be used in eligible patients undergoing EVT.³

REFERENCES
1. Smith EE, Zerna C, Solomon N, et al. Outcomes after endovascular thrombectomy with or without alteplase in routine clinical practice. JAMA Neurol. Published online June 13, 2022. doi:10.1001/jamaneurol.2022.1413
2. Podlasek A, Dhillon PS, Butt W, Grunwald IQ, England TJ. Direct mechanical thrombectomy without intravenous thrombolysis vs bridging therapy for acute ischemic stroke: a meta-analysis of randomized controlled trials. Int J Stroke. 2021;16(6):621-631. doi:10.1177/17474930211021353
3. Turc G, Tsivgoulis G, Audebert HJ, et al. European Stroke Organization (ESO)-European Society for Minimally Invasive Neurological Therapy (ESMINT) expedited recommendation on indication for intravenous thrombolysis before mechanical thrombectomy in patients with acute ischemic stroke and anterior circulation large vessel occlusion. J Neurointerv Surg. 2022;14(3):209. doi:10.1136/neurintsurg-2021-1085589