Correspondence
Centres
Countries
Year of enrolment
Number of living patients with mRS follow-up data
Percentage of original cohort (%)
Number of patients with rebleeding from target intracranial aneurysms
Mortality (%)
Percentage of live patients with mRS 3–5 (%)
Neurosurgical Endovascular clipping coiling
Neurosurgical Endovascular clipping coiling
Neurosurgical clipping
Endovascular coiling 21%
2 months1
43
··
1994–2002
1969
91·9%
··
··
6%*
6%*
31%
1 year1
43
··
1994–2002
1928
90·0%
11*
28*
8%*
7%*
23%
17%
10 years2
22
1
1994–2002
1003
46·8%
15*
51*
22%
18%
21%
17%
Notably, the figures do not include sudden deaths (outside hospitals) from rebleeds, the intracranial aneurysms causing the rebleeding were not identified (no surgeries for all patients with rebleeding), and causes of long-term mortality were mostly unrelated to the treatment. Additionally, modified Rankin Score (mRS) has not been validated for the use as an outcome comparison tool between non-surgical and surgical interventions. *After the first treatment.
Table: ISAT study results at 2 months, 1 year, and 10 years
patients with early rebleeding from the most recent analyses, the true 10 year annual rebleeding rate is and will be unclear. In summary, coiling seems to convert ruptured aneurysms to unruptured ones.1,2 Are the presented results1,2 a valid proof of long-term safety and efficacy of coiling? Do patients in fact need a new unpredictable (lifetime) treatment option for all ruptured anterior circulation intracranial aneurysms, or should this often superb intervention rather be used for a special group of patients (eg, specified by age, time from bleed, aneurysm location, comorbidities)? Hopefully, more detailed post-hoc analyses will answer some of these questions. I declare no competing interests.
Miikka Korja miikka.korja@hus.fi Department of Neurosurgery, University of Helsinki and Helsinki University Hospital, FI-00029 Helsinki, Finland 1
2
3
Molyneux AJ, Kerr RS, Yu LM, et al. International subarachnoid aneurysm trial (ISAT) of neurosurgical clipping versus endovascular coiling in 2143 patients with ruptured intracranial aneurysms: a randomised comparison of effects on survival, dependency, seizures, rebleeding, subgroups, and aneurysm occlusion. Lancet 2005; 366: 809–17. Molyneux AJ, Birks J, Clarke A, Sneade M, Kerr RSC. The durability of endovascular coiling versus neurosurgical clipping of ruptured cerebral aneurysms: 18 year follow-up of the UK cohort of the International Subarachnoid Aneurysm Trial (ISAT). Lancet 2015; 385: 691–97. Wiebers DO, Whisnant JP, Huston J 3rd, et al. Unruptured intracranial aneurysms: natural history, clinical outcome, and risks of surgical and endovascular treatment. Lancet 2003; 362: 103–10.
www.thelancet.com Vol 385 June 6, 2015
We perceive the display of the results of the ISAT 10 year follow-up1 remarkable in its methodology and erroneous in its conclusions. The 5 year ISAT follow-up data did not show a significant difference in dependency between endovascular treatment and neurosurgical treatment.2 Mortality, however, was reported higher in the neurosurgery group. We argued3 that the significant benefit of endovascular treatment regarding mortality was no longer present if pretreatment deaths, caused by difference in time from allocation to treatment (1·1 vs 1·7 days),4 are excluded. Applying the same analysis to mortality data from the 10 year follow-up, again no significance is found (OR 1·27; 95% CI 0·98–1·67, p=0·07). This is relevant in view of the generalisability towards situations in which neurosurgical treatment can be initiated earlier after subarachnoid haemorrhage. It is confusing that the authors now report a significant benefit of endovascular treatment on mortality, while also presenting a survival analysis showing no significant difference in survival (log-rank, p=0·16).1 A survival approach carries more weight methodologically because it uses the full richness of available data. Also, a distinction can be made between relative risk during the first year and thereafter; outcome after 1 year seems less favourable. The justified conclusion is that the significant advantage of
endovascular treatment relative to neurosurgical treatment only holds in the first year post-treatment. During follow-up, this benefit is no longer present. We hope this argumentation ends the debate with respect to superiority of endovascular treatment over neurosurgical treatment and opens the door to a patient-tailored treatment, in which both endovascular treatment and neurosurgical treatment are regarded viable options. We declare no competing interests.
*Nicolaas A Bakker, Nic J G M Veeger, J Marc C Van Dijk [email protected] Department of Neurosurgery (NAB, JMCVD), Department of Epidemiology (NJGMV), Trial Coordination Centre, University of Groningen, University Medical Center Groningen, 9700 RB Groningen, the Netherlands 1
2
3
4
Molyneux AJ, Birks J, Clarke A, et al. The durability of endovascular coiling versus neurosurgical clipping of ruptured cerebral aneurysms: 18 year follow-up of the UK cohort of the International Subarachnoid Aneurysm Trial (ISAT). Lancet 2015; 385: 691–97. Molyneux AJ, Kerr RS, Birks J, et al. Risk of recurrent subarachnoid haemorrhage, death, or dependence and standardised mortality ratios after clipping or coiling of an intracranial aneurysm in the International Subarachnoid Aneurysm Trial (ISAT): long-term follow-up. Lancet Neurol 2009; 8: 427–33. Bakker NA, Metzemaekers JD, Groen RJ, Mooij JJ, Van Dijk JM. International subarachnoid aneurysm trial 2009: endovascular coiling of ruptured intracranial aneurysms has no significant advantage over neurosurgical clipping. Neurosurgery 2010; 66: 961–62. Tait MJ, Critchley GR, Norris JS. How much can be concluded from the International Subarachnoid Aneurysm Trial (ISAT)? Br J Neurosurg 2007; 21: 3–6.
2251
Centres
Countries
Year of enrolment
Number of living patients with mRS follow-up data
Percentage of original cohort (%)
Number of patients with rebleeding from target intracranial aneurysms
Mortality (%)
Percentage of live patients with mRS 3–5 (%)
Neurosurgical Endovascular clipping coiling
Neurosurgical Endovascular clipping coiling
Neurosurgical clipping
Endovascular coiling 21%
2 months1
43
··
1994–2002
1969
91·9%
··
··
6%*
6%*
31%
1 year1
43
··
1994–2002
1928
90·0%
11*
28*
8%*
7%*
23%
17%
10 years2
22
1
1994–2002
1003
46·8%
15*
51*
22%
18%
21%
17%
Notably, the figures do not include sudden deaths (outside hospitals) from rebleeds, the intracranial aneurysms causing the rebleeding were not identified (no surgeries for all patients with rebleeding), and causes of long-term mortality were mostly unrelated to the treatment. Additionally, modified Rankin Score (mRS) has not been validated for the use as an outcome comparison tool between non-surgical and surgical interventions. *After the first treatment.
Table: ISAT study results at 2 months, 1 year, and 10 years
patients with early rebleeding from the most recent analyses, the true 10 year annual rebleeding rate is and will be unclear. In summary, coiling seems to convert ruptured aneurysms to unruptured ones.1,2 Are the presented results1,2 a valid proof of long-term safety and efficacy of coiling? Do patients in fact need a new unpredictable (lifetime) treatment option for all ruptured anterior circulation intracranial aneurysms, or should this often superb intervention rather be used for a special group of patients (eg, specified by age, time from bleed, aneurysm location, comorbidities)? Hopefully, more detailed post-hoc analyses will answer some of these questions. I declare no competing interests.
Miikka Korja miikka.korja@hus.fi Department of Neurosurgery, University of Helsinki and Helsinki University Hospital, FI-00029 Helsinki, Finland 1
2
3
Molyneux AJ, Kerr RS, Yu LM, et al. International subarachnoid aneurysm trial (ISAT) of neurosurgical clipping versus endovascular coiling in 2143 patients with ruptured intracranial aneurysms: a randomised comparison of effects on survival, dependency, seizures, rebleeding, subgroups, and aneurysm occlusion. Lancet 2005; 366: 809–17. Molyneux AJ, Birks J, Clarke A, Sneade M, Kerr RSC. The durability of endovascular coiling versus neurosurgical clipping of ruptured cerebral aneurysms: 18 year follow-up of the UK cohort of the International Subarachnoid Aneurysm Trial (ISAT). Lancet 2015; 385: 691–97. Wiebers DO, Whisnant JP, Huston J 3rd, et al. Unruptured intracranial aneurysms: natural history, clinical outcome, and risks of surgical and endovascular treatment. Lancet 2003; 362: 103–10.
www.thelancet.com Vol 385 June 6, 2015
We perceive the display of the results of the ISAT 10 year follow-up1 remarkable in its methodology and erroneous in its conclusions. The 5 year ISAT follow-up data did not show a significant difference in dependency between endovascular treatment and neurosurgical treatment.2 Mortality, however, was reported higher in the neurosurgery group. We argued3 that the significant benefit of endovascular treatment regarding mortality was no longer present if pretreatment deaths, caused by difference in time from allocation to treatment (1·1 vs 1·7 days),4 are excluded. Applying the same analysis to mortality data from the 10 year follow-up, again no significance is found (OR 1·27; 95% CI 0·98–1·67, p=0·07). This is relevant in view of the generalisability towards situations in which neurosurgical treatment can be initiated earlier after subarachnoid haemorrhage. It is confusing that the authors now report a significant benefit of endovascular treatment on mortality, while also presenting a survival analysis showing no significant difference in survival (log-rank, p=0·16).1 A survival approach carries more weight methodologically because it uses the full richness of available data. Also, a distinction can be made between relative risk during the first year and thereafter; outcome after 1 year seems less favourable. The justified conclusion is that the significant advantage of
endovascular treatment relative to neurosurgical treatment only holds in the first year post-treatment. During follow-up, this benefit is no longer present. We hope this argumentation ends the debate with respect to superiority of endovascular treatment over neurosurgical treatment and opens the door to a patient-tailored treatment, in which both endovascular treatment and neurosurgical treatment are regarded viable options. We declare no competing interests.
*Nicolaas A Bakker, Nic J G M Veeger, J Marc C Van Dijk [email protected] Department of Neurosurgery (NAB, JMCVD), Department of Epidemiology (NJGMV), Trial Coordination Centre, University of Groningen, University Medical Center Groningen, 9700 RB Groningen, the Netherlands 1
2
3
4
Molyneux AJ, Birks J, Clarke A, et al. The durability of endovascular coiling versus neurosurgical clipping of ruptured cerebral aneurysms: 18 year follow-up of the UK cohort of the International Subarachnoid Aneurysm Trial (ISAT). Lancet 2015; 385: 691–97. Molyneux AJ, Kerr RS, Birks J, et al. Risk of recurrent subarachnoid haemorrhage, death, or dependence and standardised mortality ratios after clipping or coiling of an intracranial aneurysm in the International Subarachnoid Aneurysm Trial (ISAT): long-term follow-up. Lancet Neurol 2009; 8: 427–33. Bakker NA, Metzemaekers JD, Groen RJ, Mooij JJ, Van Dijk JM. International subarachnoid aneurysm trial 2009: endovascular coiling of ruptured intracranial aneurysms has no significant advantage over neurosurgical clipping. Neurosurgery 2010; 66: 961–62. Tait MJ, Critchley GR, Norris JS. How much can be concluded from the International Subarachnoid Aneurysm Trial (ISAT)? Br J Neurosurg 2007; 21: 3–6.
2251
