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(2020)Objective
To assess whether endovascular thrombectomy alone is noninferior to IV alteplase plus thrombectomy in anterior circulation LVO stroke within 4.5 hours.
Study Summary
Intervention
Endovascular thrombectomy alone vs. IV alteplase (0.9 mg/kg) followed by thrombectomy. Alteplase administered within 4.5 hours from onset; thrombectomy performed with stent retriever or aspiration.
Inclusion Criteria
Age ≥18, acute ischemic stroke due to LVO (intracranial ICA or M1/M2 MCA), NIHSS ≥2, eligible for alteplase within 4.5 hours of onset, mRS ≤2 pre-stroke.
Study Design
Arms: Thrombectomy Alone vs. Alteplase + Thrombectomy
Patients per Arm: Thrombectomy: 327, Combined: 329
Outcome
Bottom Line
Endovascular thrombectomy alone was noninferior to the combination of intravenous alteplase followed by endovascular thrombectomy for functional outcome at 90 days in Chinese patients with acute ischemic stroke.
Major Points
- The trial was a prospective, randomized, open-label trial with blinded outcome assessment.
- A total of 656 patients with acute ischemic stroke from large-vessel occlusion in the anterior circulation were randomized 1:1 to either endovascular thrombectomy alone or endovascular thrombectomy preceded by intravenous alteplase.
- The primary outcome was the score on the modified Rankin scale at 90 days, assessed for noninferiority.
- Endovascular thrombectomy alone was found to be noninferior, with an adjusted common odds ratio of 1.07 (95% CI, 0.81 to 1.40).
- Mortality at 90 days was similar between the groups (17.7% vs. 18.8%).
- The percentage of patients with successful reperfusion before thrombectomy was significantly lower in the thrombectomy-alone group (2.4% vs. 7.0%).
- There was no significant difference in the rates of serious adverse events, including symptomatic intracranial hemorrhage (4.3% vs. 6.1%).
Study Design
- Study Type
- Randomized, open-label, multicenter, prospective trial
- Randomization
- Yes
- Blinding
- Outcome committee and imaging core laboratory were blinded to treatment-group assignments.
- Sample Size
- 656
- Follow-up
- 90 days
- Centers
- 41
- Countries
- China, Netherlands, Canada
Primary Outcome
Definition: Score on the modified Rankin scale (mRS) at 90 days. The scale ranges from 0 (no symptoms) to 6 (death).
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| Median mRS score: 3 (IQR, 2-5) | Median mRS score: 3 (IQR, 2-5) | - (0.81 to 1.40) | 0.04 for noninferiority |
Limitations & Criticisms
- The trial was designed based on 2015 guidelines and used stent retrievers and standard doses of alteplase, which may not reflect current practices using newer devices and drugs like tenecteplase.
- The noninferiority margin of 0.8 was considered generous, and the wide confidence intervals do not rule out a potential benefit of combined therapy.
- The short time allowed for alteplase to act before thrombectomy and the continuation of infusion during the procedure may have obscured the full effects of the drug.
- The results may not be generalizable to non-Asian populations due to differences in stroke causes.
- Longer workflow times in China due to prehospital triage and informed consent requirements may have influenced the results.
Citation
N Engl J Med 2020;382-1981-93. DOI: 10.1056/NEJMoa2001123