90-day functional outcomes similar in endovascular thrombectomy regardless of alteplase use
Among patients with acute ischemic stroke from large-vessel occlusion, endovascular thrombectomy alone was noninferior for 90-day functional outcomes to IV alteplase administered within 4.5 hours from symptom onset plus endovascular thrombectomy.
For this study published in The New England Journal of Medicine, investigators randomly assigned 656 Chinese patients with acute ischemic stroke from large-vessel occlusion in the anterior circulation to IV alteplase (Activase, Genentech) plus endovascular thrombectomy or endovascular thrombectomy alone. The primary outcome was difference in functional outcomes at 90 days as assessed by the modified Rankin Scale score.
Endovascular thrombectomy alone was found to be noninferior to IV alteplase plus endovascular thrombectomy for 90-day functional outcomes (adjusted OR = 1.07; 95% CI, 0.81-1.4; P for noninferiority = .04).
Successful reperfusion and hemorrhage
However, patients who underwent endovascular thrombectomy alone experienced a lower rate of successful reperfusion before thrombectomy compared with the combination intervention (2.4% vs. 7%; OR = 0.33; 95% CI, 0.14-0.74) and of overall successful reperfusion (79.4% vs. 84.5%; OR = 0.7; 95% CI, 0.47-1.06).
There was no difference between the groups in 90-day mortality rate (thrombectomy, 17.7%; combination, 18.8%; RR = 0.94; 95% CI, 0.68-1.3).
“In patients with acute ischemic stroke due to large-vessel occlusion in the anterior circulation who were eligible for treatment with both intravenous alteplase and endovascular thrombectomy according to most guidelines, direct intervention with intra-arterial thrombectomy was noninferior to the combination of initial intravenous alteplase followed by endovascular thrombectomy,” Pengfei Yang, MD, assistant director of the department of neurosurgery at Changhai Hospital of Shanghai, and colleagues wrote. “Because the lower boundary of the 95% confidence interval for the common odds ratio comparing the modified Rankin Scale scores at 90 days was just above the prespecified value of 0.8 in the unadjusted and adjusted analyses, the results do not rule out a benefit of alteplase.”
In other findings, the between-group difference was similar for prevalence of both symptomatic intracranial hemorrhage (4.3% vs. 6.1%; RR = 0.7; 95% CI, 0.36-1.37) and asymptomatic hemorrhage (33.3% vs. 36.2%; RR = 0.92; 95% CI, 0.75-1.14), according to the study.
Stick with the guidelines
“Noninferiority was established; however, the margin that was used to declare noninferiority was generous, and the confidence intervals did not exclude a benefit of approximately 20% in the combination-therapy group,” Gregory W. Albers, MD, professor of neurosurgery at the Stanford University Medical Center, wrote in a related editorial.
“The mismatch between the high percentages of patients with reperfusion and the much smaller percentages of patients with clinical recovery in thrombectomy studies suggests that a substantial volume of brain tissue is already irreversibly injured in many patients by the time reperfusion occurs,” Albers wrote. “To improve outcomes in future stroke trials, adjunctive therapies, such as thrombolytic or neuroprotective agents, might be started early, at the primary stroke center or in the prehospital setting. Until more data are available, it is appropriate to follow current guidelines that recommend that all eligible patients receive alteplase before thrombectomy.” – by Scott Buzby
Disclosures: Yang reports he received grants from the National Natural Science Foundation of China and the Shanghai Municipal Health Commission. Albers reports he received personal fees from Biogen, Genentech, IschemaView, Janssen, Johnson & Johnson, Medtronic, NuVox, Omniox, Portola and Prolong Pharma. Please see the study for all other authors’ relevant financial disclosures.
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Albers GW. N Engl J Med. 2020;doi:10.1056/NEJMe2004550.
Yang P, et al. N Engl J Med. 2020;doi:10.1056/NEJMoa2001123.