The Impact of Treatment Delay on Outcome in the International Subarachnoid Aneurysm Trial (ISAT): Additional Analyses Comparing Neurosurgical Clipping vs. Endovascular Coiling

Abstract

Background: ISAT demonstrated that 1 year after aneurysmal subarachnoid haemorrhage (aSAH), coiling resulted in a significantly better clinical outcome (death or dependency at 1 year) than clipping. After 5 years, this difference did not reach statistical significance but mortality (secondary endpoint) was still higher in the clipping group. Here, we present additional analyses, reporting the outcome after excluding pre-treatment death and/or re-bleeding. Methods: Outcome measures were death or dependency, and death alone, 1 and 5 years after treatment. We investigated outcome after i. exclusion of all pre-treatment deaths ii. exclusion of all pre-treatment rebleedings iii. 'as-treated' analysis and iv. as-treated analysis including good-grade patients (WFNS 0-2). Treatment differences were assessed using relative risks. Exploratory analyses were used to investigate the relation between treatment delay and outcome. Findings: After exclusion of pre-treatment deaths, coiling was favourable over clipping at 1-year follow-up for death or dependency (RR 0·77; 95%CI 0·67-0·89), but not for death alone (RR 0·88; 95%CI 0·66-1·19). After 5 years, no significant differences were observed, neither for death or dependency (RR 0·88; 95%CI 0·77-1·02), nor death alone (RR 0·82; 95%CI 0·64-1·05). Analyses ii. and iii showed a similar picture. In good-grade patients coiling remained favourable over clipping in long-term. Time between randomisation and treatment was significantly longer in the clipping arm (mean 1·7 versus 1·1 days; p<0·0001), in which respectively 17 patients died because of rebleeding vs. 6 in the endovascular arm (RR=2·81; 95%CI 1·11-7·11). Interpretation: These additional analyses support the conclusion of ISAT that at 1-year follow-up after aSAH, coiling leads to a better outcome than clipping. After 5 years however, with pre-treatment deaths and/or re-bleedings excluded, the difference between coiling and clipping was no longer significant. The high number of pre-treatment deaths in the clipping group highlights the importance of urgent aneurysm treatment to prevent early rebleeding. Funding: None. Declaration of Interest: None. Ethical Approval: All procedures performed in the study involving human participants were in accordance with the ethical standards of the participating institutions and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The protocol was approved by local Institutional Review Boards, and all patients (or representatives) provided written informed consent prior to participation.