PDF: ANGEL-ASPECT
(2023)Objective
Mechanical thrombectomy in patients with low ASPECTS scores.
Study Summary
Intervention
Mechanical thrombectomy using the latest generation stent retrievers across varying ASPECTS scores.
Inclusion Criteria
Patients with acute ischemic stroke, presenting within 6 hours of symptom onset, with ASPECTS scores ranging from 2 to 10.
Study Design
Arms: Low ASPECTS (3-5) vs. High ASPECTS (6-10)
Patients per Arm: Low ASPECTS: 200, High ASPECTS: 200
Outcome
Bottom Line
Endovascular therapy significantly improved functional outcomes at 90 days and reduced mortality in patients with acute ischemic stroke and large infarcts compared to best medical management. The benefit was consistent across various subgroups, despite a numerically higher incidence of symptomatic intracranial hemorrhage.
Major Points
- 456 patients with acute ischemic stroke and ASPECTS 3-5 were randomly assigned (229 to endovascular therapy, 227 to best medical management).
- The median modified Rankin Scale score at 90 days was 3 in the endovascular therapy group and 5 in the best medical management group (adjusted common odds ratio, 2.40; 95% CI, 1.62 to 3.56; P<0.001).
- The rate of functional independence (mRS 0-2) at 90 days was 46% in the endovascular therapy group vs 22% in the best medical management group.
- Death from any cause at 90 days occurred in 26% in the endovascular therapy group vs 40% in the best medical management group (adjusted risk ratio, 0.68; 95% CI, 0.49 to 0.94).
- Symptomatic intracranial hemorrhage occurred in 6.0% in the endovascular therapy group and 2.6% in the best medical management group (adjusted risk ratio, 2.37; 95% CI, 0.86 to 6.54).
- Successful reperfusion (mTICI 2b-3) was achieved in 84% of the endovascular therapy group.
- The trial was stopped early due to clear evidence of benefit in the endovascular therapy group.
Study Design
- Study Type
- Multicenter, prospective, randomized, open-label, blinded-endpoint, superiority trial (Phase 3)
- Randomization
- Yes
- Blinding
- Blinded-endpoint design (outcome assessors were blinded to treatment assignment; core imaging laboratory staff were blinded).
- Sample Size
- 456
- Follow-up
- 90 days (primary outcome)
- Centers
- 46
- Countries
- China
Primary Outcome
Definition: Ordinal shift on the modified Rankin Scale (mRS) at 90 days (scores range from 0 to 6, with higher scores indicating greater disability).
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| Median mRS: 5 (IQR 3-6) | Median mRS: 3 (IQR 2-6) | 2.4 (1.62 to 3.56) | <0.001 |
Limitations & Criticisms
- The trial was stopped early due to clear evidence of benefit in the endovascular therapy group, which means it did not reach its full planned sample size. This may limit the power to detect smaller effects and the precision of the estimated treatment effects.
- The study did not achieve blinding of patients or site personnel due to the nature of the intervention, which could introduce bias, though outcome assessment was blinded.
- The study population was homogeneous, consisting of patients from Chinese stroke centers, which may limit generalizability to other ethnic groups or health-care systems.
- The use of ASPECTs as the sole imaging selection criterion for large infarcts has limitations and might not fully capture the complexity of infarct core physiology.
- The study's definition of 'large infarct' (ASPECTS 3-5) might not align with other trials, making direct comparisons challenging.
- The numerically higher incidence of symptomatic intracranial hemorrhage in the endovascular therapy group, while not statistically significant, remains a concern.
Citation
N Engl J Med 2023;388:1259-71. DOI: 10.1056/NEJMoa2213790