By Matthew E. Fink, MD

Louis and Gertrude Feil Professor and Chair, Department of Neurology, Associate Dean for Clinical Affairs, New York Presbyterian/Weill Cornell Medical College

Dr. Fink reports no financial relationships relevant to this field of study.

SOURCE: 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.

Endovascular mechanical thrombectomy has become the standard treatment for patients with acute ischemic stroke caused by large vessel occlusion in both the anterior and posterior circulations. This is predicated on the ability to perform the procedure in a timely fashion or based on a mismatch between the size of infarction and brain perfusion.

Endovascular thrombectomy has better outcomes than intravenous thrombolysis alone for large vessel occlusion, and an ongoing debate exists regarding the need for administering intravenous alteplase initially, followed by thrombectomy, or moving immediately to thrombectomy alone.

In support of giving alteplase first is the observation that it may increase early reperfusion of the ischemic area and dissolve residual thrombi after endovascular thrombectomy. However, there is a risk that intravenous alteplase may delay mechanical thrombectomy and increase the risk of cerebral hemorrhage. These investigators undertook a strategy to determine whether endovascular thrombectomy alone would be noninferior to combined treatment with endovascular thrombectomy preceded by intravenous alteplase in patients with large vessel occlusion.

This study was performed in 41 academic tertiary care centers in China. Patients with acute ischemic stroke from large vessel occlusion in the anterior circulation were randomly assigned in 1:1 ratio to undergo endovascular thrombectomy alone or endovascular thrombectomy preceded by intravenous alteplase within 4.5 hours after symptom onset. The primary analysis for noninferiority assessed the differences between the groups in the distribution of the modified Rankin scale scores at 90 days on the basis of a lower boundary of the 95% confidence interval of the odds ratio (OR) ≤ 0.8. Secondary outcomes also were assessed, including death and reperfusion of the ischemic area.

Six hundred fifty-six patients were enrolled, with 327 assigned to the thrombectomy-alone group and 329 assigned to the combination therapy group. In regard to the primary outcome, endovascular thrombectomy alone was deemed noninferior to combined intravenous alteplase and endovascular thrombectomy (OR, 1.07; P = 0.04), but also was associated with a lower percentage of patients with successful reperfusion before thrombectomy (2.4% vs. 7.0%) as well as a lower overall successful reperfusion (79.4% vs. 84.5%). There was no difference in mortality at 90 days (17.7% vs. 18.8%).

In an accompanying editorial (published May 6, 2020, on NEJM.org), Dr. Greg Albers noted that the timing of endovascular thrombectomy overlapped with the administration of alteplase, which might have diminished the thrombolytic effect of the medication. Also, the successful perfusion rate in the thrombectomy-alone group was lower than in other large published studies. There was no difference in intracerebral hemorrhages, nor a difference in procedure-related ischemic stroke.

Thrombolysis may have been delayed because all patients were treated at a tertiary hospital, and the effects of earlier administration of alteplase, which is the standard in North America, could not be assessed.

Dr. Albers closed his editorial with the following statement: “Until more data are available, it is appropriate to follow current guidelines that recommend that all eligible patients receive alteplase before thrombectomy.”