Endovascular Thrombectomy with or without Intravenous Alteplase in Acute Stroke

N Engl J Med. 2020 May 21;382(21):1981-1993. doi: 10.1056/NEJMoa2001123. Epub 2020 May 6.

Abstract

Background: In acute ischemic stroke, there is uncertainty regarding the benefit and risk of administering intravenous alteplase before endovascular thrombectomy.

Methods: We conducted a trial at 41 academic tertiary care centers in China to evaluate endovascular thrombectomy with or without intravenous alteplase in patients with acute ischemic stroke. Patients with acute ischemic stroke from large-vessel occlusion in the anterior circulation were randomly assigned in a 1:1 ratio to undergo endovascular thrombectomy alone (thrombectomy-alone group) or endovascular thrombectomy preceded by intravenous alteplase, at a dose of 0.9 mg per kilogram of body weight, administered within 4.5 hours after symptom onset (combination-therapy group). The primary analysis for noninferiority assessed the between-group difference in the distribution of the modified Rankin scale scores (range, 0 [no symptoms] to 6 [death]) at 90 days on the basis of a lower boundary of the 95% confidence interval of the adjusted common odds ratio equal to or larger than 0.8. We assessed various secondary outcomes, including death and reperfusion of the ischemic area.

Results: Of 1586 patients screened, 656 were enrolled, with 327 patients assigned to the thrombectomy-alone group and 329 assigned to the combination-therapy group. Endovascular thrombectomy alone was noninferior to combined intravenous alteplase and endovascular thrombectomy with regard to the primary outcome (adjusted common odds ratio, 1.07; 95% confidence interval, 0.81 to 1.40; P = 0.04 for noninferiority) but was associated with lower percentages of patients with successful reperfusion before thrombectomy (2.4% vs. 7.0%) and overall successful reperfusion (79.4% vs. 84.5%). Mortality at 90 days was 17.7% in the thrombectomy-alone group and 18.8% in the combination-therapy group.

Conclusions: In Chinese patients with acute ischemic stroke from large-vessel occlusion, endovascular thrombectomy alone was noninferior with regard to functional outcome, within a 20% margin of confidence, to endovascular thrombectomy preceded by intravenous alteplase administered within 4.5 hours after symptom onset. (Funded by the Stroke Prevention Project of the National Health Commission of the People's Republic of China and the Wu Jieping Medical Foundation; DIRECT-MT ClinicalTrials.gov number, NCT03469206.).

Publication types

  • Equivalence Trial
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Cerebral Hemorrhage / etiology
  • China
  • Combined Modality Therapy
  • Confidence Intervals
  • Endovascular Procedures
  • Female
  • Fibrinolytic Agents / adverse effects
  • Fibrinolytic Agents / therapeutic use*
  • Humans
  • Infusions, Intravenous
  • Male
  • Middle Aged
  • Reperfusion / methods
  • Stroke / drug therapy*
  • Stroke / surgery*
  • Thrombectomy / adverse effects
  • Thrombectomy / methods*
  • Time-to-Treatment
  • Tissue Plasminogen Activator / adverse effects
  • Tissue Plasminogen Activator / therapeutic use*
  • Treatment Outcome

Substances

  • Fibrinolytic Agents
  • Tissue Plasminogen Activator

Associated data

  • ClinicalTrials.gov/NCT03469206