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(2005)Objective
To determine whether endovascular coil treatment compared with neurosurgical clipping reduces the proportion of patients dead or dependent at 1 year in patients with ruptured intracranial aneurysms suitable for both treatments.
Study Summary
• Survival benefit maintained for up to 7 years (log rank p=0.03)
• Risk of epilepsy substantially lower with endovascular treatment, but late rebleeding risk slightly higher
Intervention
Patients randomly assigned to neurosurgical clipping or endovascular coiling with detachable platinum coils
Inclusion Criteria
Subarachnoid hemorrhage from intracranial aneurysm, suitable for both endovascular and neurosurgical treatment, uncertainty by responsible neurosurgeon and neuroradiologist about best treatment
Study Design
Arms: Endovascular coiling vs Neurosurgical clipping
Patients per Arm: 1073 endovascular, 1070 neurosurgery
Outcome
• Death at 1 year: 8.0% endovascular vs 9.9% neurosurgery
• Rebleeding after 1 year: 7 patients endovascular vs 2 neurosurgery (0.2% per patient-year)
• Seizures after procedure: significantly lower in endovascular group (RR 0.52)
Bottom Line
In patients with ruptured intracranial aneurysms suitable for both treatments, endovascular coiling is more likely to result in independent survival at 1 year than neurosurgical clipping, with an absolute risk reduction of 7.4% (95% CI 3.6-11.2, p=0.0001) and relative risk reduction of 23.9% (12.4-33.9). The survival benefit continues for at least 7 years (log rank p=0.03). The risk of epilepsy is substantially lower with endovascular treatment (RR 0.52, 95% CI 0.37-0.74). The risk of late rebleeding is low (0.2% per patient-year after first year) but slightly more common after endovascular coiling than after neurosurgical clipping. At first follow-up angiography, 66% of coiled aneurysms showed complete occlusion compared to 82% of clipped aneurysms (in selected patients who had follow-up angiography).
Major Points
- Multicenter randomized controlled trial at 42 neurosurgical centres, mainly in UK and Europe
- 2143 patients with ruptured intracranial aneurysms randomized between recruitment closure
- Patients eligible only if responsible neurosurgeon and neuroradiologist were uncertain about best treatment (equipoise)
- 88% of patients in good clinical grade (WFNS 1-2) at enrollment
- 95% of aneurysms in anterior circulation, 90% smaller than 10 mm
- Primary outcome: death or dependency (mRS 3-6) at 1 year
- At 1 year: 23.5% dead or dependent in endovascular group vs 30.9% in neurosurgery group (RR 0.76, 95% CI 0.66-0.87, p=0.0001)
- Absolute risk reduction 7.4% (3.6-11.2), relative risk reduction 23.9% (12.4-33.9)
- Case fatality at 1 year: 8.0% endovascular vs 9.9% neurosurgery
- Survival advantage maintained for up to 7 years (log rank p=0.03)
- Mean follow-up 4 years, with 6542 patient-years of follow-up after 1 year
- Rebleeding from target aneurysm after 1 year: 7 patients endovascular vs 2 neurosurgery (0.2% per patient-year)
- Seizures significantly reduced with endovascular treatment (RR 0.52, 95% CI 0.37-0.74)
- Follow-up angiography in 881 of 988 surviving endovascular patients (89%): 66% complete occlusion, 26% neck remnant/subtotal, 8% incomplete
- Follow-up angiography in 450 of 965 surviving neurosurgery patients (47%): 82% complete occlusion, 12% neck remnant, 6% incomplete
- Treatment effect heterogeneous by age, WFNS grade, and aneurysm location, but no robust evidence that neurosurgery has advantages for any subgroup
- Trial closed early after interim analysis showed benefit of endovascular treatment
Study Design
- Study Type
- Prospective randomized controlled trial, partially blinded
- Randomization
- Yes
- Blinding
- Outcome assessors (certified examiners and neuropsychologist) were unaware of treatment assignments. Blinded assessment of rebleeding not possible because clips, coils, and craniotomy evidence visible on CT scans. Two independent investigators (neurosurgeon and neuroradiologist) judged all rebleeding and intracranial hemorrhage events.
- Sample Size
- 2143
- Follow-up
- 1 year primary outcome, with continued follow-up to 7 years (mean 4 years)
- Centers
- 42
- Countries
- United Kingdom, Europe, Other international sites
Primary Outcome
Definition: Death or dependency defined by modified Rankin Scale (mRS) score of 3-6 at 1 year
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| 326 of 1055 patients (30.9%) | 250 of 1063 patients (23.5%) | - (0.66-0.87) | 0.0001 |
Limitations & Criticisms
- Only patients for whom there was uncertainty about best treatment were enrolled - approximately 80% of screened aneurysms excluded
- Highly variable enrollment rates between centers
- Selection bias concerns - patients clearly more suitable for one treatment were not randomized
- Questions about whether surgical expertise represented the best that neurosurgery had to offer
- Applicability concerns - results may not generalize to all patients with subarachnoid hemorrhage
- More patients in surgical group had rebleeding before treatment (23 vs 14)
- Follow-up angiography not mandatory after neurosurgical clipping (only 47% had angiography), creating potential selection bias in angiographic outcome comparison
- Blinded assessment of rebleeding not possible due to visibility of clips and coils on imaging
- Long-term durability of coil occlusion uncertain beyond 7 years
- Angiographic occlusion rates better with clipping (82% complete) than coiling (66% complete)
- Small numbers in some subgroups (elderly, poor grade) limit interpretation
- Trial predominantly enrolled good-grade patients (88% WFNS 1-2) and small anterior circulation aneurysms (90% <10mm)
- Limited data on giant or complex aneurysms
- No data on cost-effectiveness presented in this publication
Citation
Lancet 2005; 366: 809-17