Impact of Treatment Delay on Outcome in the International Subarachnoid Aneurysm Trial

Background and Purpose - ISAT (International Subarachnoid Aneurysm Trial) demonstrated that 1 year after aneurysmal subarachnoid hemorrhage, coiling resulted in a significantly better clinical outcome than clipping. After 5 years, this difference did not reach statistical significance, but mortality was still higher in the clipping group. Here, we present additional analyses, reporting outcome after excluding pretreatment deaths. Methods - Outcome measures were death with or without dependency at 1 and 5 years after treatment, after exclusion of all pretreatment deaths. Treatment differences were assessed using relative risks (RRs). With sensitivity and exploratory analyses, the relation between treatment delay and outcome was analyzed. Results - After exclusion of pretreatment deaths, at 1-year follow-up coiling was favorable over clipping 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 for death alone (RR, 0.82 [95% CI, 0.64-1.05]). Sensitivity analyses showed a similar picture. In good-grade patients, coiling remained favorable over clipping in the long-term. Time between randomization and treatment was significantly longer in the clipping arm (mean 1.7 versus 1.1 days; P<0.0001), during which 17 patients died because of rebleeding versus 6 pretreatment deaths in the endovascular arm (RR, 2.81 [95% CI, 1.11-7.11]). Conclusions - These additional analyses support the conclusion of ISAT that at 1-year follow-up after aneurysmal subarachnoid hemorrhage coiling has a better outcome than clipping. After 5 years, with pretreatment mortality excluded, the difference between coiling and clipping is not significant. The high number of pretreatment deaths in the clipping group highlights the importance of urgent aneurysm treatment to prevent early rebleeding

Prediction of two month modified Rankin Scale with an ordinal prediction model in patients with aneurysmal subarachnoid haemorrhage

Background. Aneurysmal subarachnoid haemorrhage (aSAH) is a devastating event with a frequently disabling outcome. Our aim was to develop a prognostic model to predict an ordinal clinical outcome at two months in patients with aSAH. Methods. We studied patients enrolled in the International Subarachnoid Aneurysm Trial (ISAT), a randomized multicentre trial to compare coiling and clipping in aSAH patients. Several models were explored to estimate a patient's outcome according to the modified Rankin Scale (mRS) at two months after aSAH. Our final model was validated internally with bootstrapping techniques. Results. The study population comprised of 2,128 patients of whom 159 patients died within 2 months (8%). Multivariable proportional odds analysis identified World Federation of Neurosurgical Societies (WFNS) grade as the most important predictor, followed by age, sex, lumen size of the aneurysm, Fisher grade, vasospasm on angiography, and treatment modality. The model discriminated moderately between those with poor and good mRS scores (c statistic = 0.65), with minor optimism according to bootstrap re-sampling (optimism corrected c statistic = 0.64). Conclusion. We presented a calibrated and internally validated ordinal prognostic model to predict two month mRS in aSAH patients who survived the early stage up till a treatment decision.

The costs and prognostic characteristics of ischaemic neurological deficit due to subarachnoid haemorrhage in the United Kingdom. Evidence from the MRC International Subarachnoid Aneurysm Trial.

BACKGROUND: Delayed ischaemic neurological deficit (DID) following subarachnoid haemorrhage from aneurysm rupture (aSAH) is a serious complication and a major cause of mortality and morbidity. No empirical estimates of resource use and costs of patients with delayed ischaemic deficit compared to those without have been reported to date. METHODS: A detailed cost analysis of the UK National Health Service health care costs of DID was performed using resource use data from the International Subarachnoid Aneurysm Trial (ISAT) over the 24 months following haemorrhage. Resource use categories included direct health care and employment-related costs. A prognostic model of baseline predictors of DID and overall total health care costs was also constructed. RESULTS: Mean (standard deviation) total health care costs at 24 months follow-up were estimated to be pound sterling 28175 (pound sterling 26773) in the DID group and pound sterling 18805 (pound sterling 17287) in the no DID group, a significant difference (95 % confidence interval) of pound sterling 9370 (pound sterling 6880 to pound sterling 12516). This cost difference was driven by statistically significant differences on imaging and investigations, longer length of stay and higher cost of complications and adverse events experienced by patients with DID. Patients with DID also spent on average 62 days less in paid employment than patients without this complication. The prognostic model found CT Fisher grading, WFNS grade, aneurysm location and time from aSAH to intervention statistically significant baseline predictors of delayed ischaemic deficit. CONCLUSION: Patients who developed DID incurred substantially higher costs and a significantly slower resumption of employment than patients without at 24 months follow-up after aSAH

Effect of Carotid Endarterectomy on 20 Year Incidence of Recorded Dementia : A Randomised Trial

Objective: Stroke and carotid atherosclerosis are associated with dementia. Carotid endarterectomy (CEA) reduces stroke risk, although its effect on later dementia is uncertain. Participants in the Asymptomatic Carotid Surgery Trial (ACST-1), randomly allocated to immediate vs. deferral of CEA (i.e., no intervention unless or until triggered by ipsilateral transient ischaemic attack or stroke), were followed, to study effects on dementia. Methods: From 1993 to 2003, ACST-1 included 3 120 participants with asymptomatic tight carotid stenosis. All UK and Swedish patients (n = 1 601; 796 immediate vs. 805 deferral) were followed with trial records, national electronic health record linkage, and (UK only) by post and telephone. Cumulative incidence and competing risk analyses were used to measure the effects of risk factors and CEA on dementia risk. Intention to treat analyses yielded hazard ratios (HRs; immediate vs. deferral) of dementia. Results: The median follow up was 19.4 years (interquartile range 16.9 – 21.7). Dementia was recorded in 107 immediate CEA patients and 115 allocated delayed surgery; 1 290 patients died (1 091 [538 vs. 536] before any dementia diagnosis). Dementia incidence rose with age and with female sex (men: 8.3% aged .05). Conclusion: CEA was not associated with significant reductions in the long term hazards of dementia, but the CI did not exclude a proportional benefit or hazard of about 25%