What did the large core thrombectomy stroke trials show regarding the effectiveness of mechanical thrombectomy in acute ischemic stroke due to large vessel occlusion?

Large Core Thrombectomy Stroke Trials: Key Findings and Implications

Mechanical thrombectomy significantly improves functional outcomes in patients with large-core ischemic stroke compared to medical management alone, with a 12% absolute increase in functional independence and 16.6% increase in independent ambulation across multiple trials.

Definition and Trial Overview

Large-core ischemic stroke refers to strokes with substantial completed infarction, typically defined as:

• ASPECTS score <6 on CT imaging
• Core volumes >50-70mL on advanced imaging

The recent landmark trials evaluating mechanical thrombectomy for large-core strokes include:

• RESCUE-Japan LIMIT
• ANGEL-ASPECT
• SELECT2
• TENSION
• TESLA
• LASTE

Key Outcomes from Large-Core Trials

Primary Benefits

• Functional Independence (mRS 0-2): 19.5% in thrombectomy group vs. 7.5% in medical management group 1
• Independent Ambulation: 36.5% in thrombectomy group vs. 19.9% in medical management group 1
• Combined Analysis: OR 1.57 (95% CI, 1.40-1.76) favoring thrombectomy for favorable shift in mRS at 90 days 1

Safety Outcomes

• Mortality: Lower in 4 of 6 trials for thrombectomy, with statistically significant reductions in TENSION and LASTE trials 1
• Symptomatic Hemorrhage: 5.5% with thrombectomy vs. 3.3% with medical management (difference not statistically significant) 1
• Decompressive Craniectomy: No consistent difference between treatment approaches (11.1% with thrombectomy vs. 9.5% with medical management) 1

Evolution of Thrombectomy Evidence

Early Window Trials (0-6 hours)

• Initial trials excluded patients with large-core infarcts (ASPECTS <6)
• Pooled analysis from HERMES collaboration showed benefit in patients not treated with IV alteplase (cOR 2.43; 95% CI, 1.30-4.55) 1
• Benefit demonstrated across age groups, including those ≥80 years old 1

Extended Window Trials (6-24 hours)

• DAWN Trial: Used clinical-imaging mismatch criteria for patient selection between 6-24 hours

  • 49% functional independence with thrombectomy vs. 13% with medical management 1

• DEFUSE 3 Trial: Used perfusion-core mismatch criteria for selection between 6-16 hours

  • 44.6% functional independence with thrombectomy vs. 16.7% with medical management 1

Bridging Thrombolysis vs. Direct Thrombectomy

• Bridging thrombolysis (IV thrombolysis + thrombectomy) achieved better outcomes than direct thrombectomy alone 1:
  • Higher functional independence at 90 days (OR=1.43 [95% CI, 1.28-1.61])
  • Lower mortality at 90 days (OR=0.67 [95% CI, 0.60-0.75])
  • Higher successful recanalization rates (OR=1.23 [95% CI, 1.07-1.42])
  • No significant difference in symptomatic intracranial hemorrhage 1

Technical Considerations

• Reperfusion Goal: Modified TICI 2b/3 angiographic result to maximize probability of good functional outcome 1
• Vessel Occlusion Location: Strong evidence for ICA and M1 MCA occlusions; less certain but reasonable for M2/M3 MCA, anterior cerebral, vertebral, basilar, and posterior cerebral artery occlusions 1

Common Complications and Management

• Vasospasm: Occurred in 23% of thrombectomy patients 2
• Embolization to new territory: Occurred in 6% of thrombectomy patients 2
• Symptomatic intracranial hemorrhage: Similar rates between thrombectomy and medical management 3

Clinical Implications and Pitfalls

Key Pitfalls to Avoid:

1. Delaying treatment: Time to reperfusion remains critical for outcomes
2. Excluding elderly patients: Benefits seen across age groups, though data for those ≥90 years is limited
3. Ignoring bridging thrombolysis: IV thrombolysis should still be administered when indicated
4. Treating beyond established time windows: Current evidence supports treatment up to 24 hours in selected patients, with outcomes worsening beyond this window 4

Patient Selection Considerations:

• Strict adherence to trial eligibility criteria is essential when selecting patients beyond 6 hours 1
• For extended window patients, either DAWN or DEFUSE-3 criteria should be used 1
• Advanced imaging (CT perfusion or MRI diffusion/perfusion) is mandatory for extended window cases 5

The large-core thrombectomy trials have expanded the population that can benefit from mechanical thrombectomy, demonstrating that even patients with substantial completed infarction can achieve better functional outcomes with intervention compared to medical management alone.