International Subarachnoid Aneurysm Trial (ISAT) of neurosurgical clipping versus endovascular coiling in 2143 patients with ruptured intracranial aneurysms: a randomised trial. Outcomes of early endovascular versus surgical treatment of ruptured cerebral aneurysms. A prospective randomized study. Comparison of surveillance vs Aortic Endografting for Small Aneurysm Repair (CAESAR) trial: study design and progress. Randomized pilot trial of postoperative aspirin in subarachnoid hemorrhage. Benefits and risks of antifibrinolytic therapy in the management of ruptured intracranial aneurysms. A double-blind placebo-controlled study. Influence of screening on the incidence of ruptured abdominal aortic aneurysm: 5-year results of a randomized controlled study. Failure of fibrinolytic endoventricular treatment to prevent neonatal post-haemorrhagic hydrocephalus. A case-control trial. Overall management of vascular lesions considered treatable with extracranial-intracranial bypass: part 1. Internal carotid occlusion. Decompressive Surgery for the Treatment of Malignant Infarction of the Middle Cerebral Artery (DESTINY): a randomized, controlled trial.
Endovascular detachable coil treatment is being increasingly used as an alternative to craniotomy and clipping for some ruptured intracranial aneurysms, although the relative benefits of these two approaches have yet to be established. We undertook a randomised, multicentre trial to compare the safety and efficacy of endovascular coiling with standard neurosurgical clipping for such aneurysms judged to be suitable for both treatments.
                We enrolled 2143 patients with ruptured intracranial aneurysms and randomly assigned them to neurosurgical clipping (n=1070) or endovascular treatment by detachable platinum coils (n=1073). Clinical outcomes were assessed at 2 months and at 1 year with interim ascertainment of rebleeds and death. The primary outcome was the proportion of patients with a modified Rankin scale score of 3-6 (dependency or death) at 1 year. Trial recruitment was stopped by the steering committee after a planned interim analysis. Analysis was per protocol.
                190 of 801 (23.7%) patients allocated endovascular treatment were dependent or dead at 1 year compared with 243 of 793 (30.6%) allocated neurosurgical treatment (p=0.0019). The relative and absolute risk reductions in dependency or death after allocation to an endovascular versus neurosurgical treatment were 22.6% (95% CI 8.9-34.2) and 6.9% (2.5-11.3), respectively. The risk of rebleeding from the ruptured aneurysm after 1 year was two per 1276 and zero per 1081 patient-years for patients allocated endovascular and neurosurgical treatment, respectively.
                In patients with a ruptured intracranial aneurysm, for which endovascular coiling and neurosurgical clipping are therapeutic options, the outcome in terms of survival free of disability at 1 year is significantly better with endovascular coiling. The data available to date suggest that the long-term risks of further bleeding from the treated aneurysm are low with either therapy, although somewhat more frequent with endovascular coiling. This prospective study was conducted to compare the outcomes of surgical clipping and endovascular treatment in acute (<72 hours) aneurysmal subarachnoid hemorrhage (SAH).
                One hundred nine consecutive patients were randomly assigned to either surgical (n=57) or endovascular (n=52) treatment. Clinical and neuropsychological outcome was assessed at 3 and 12 months after treatment; MRI of the brain was performed at 12 months. Follow-up angiography was scheduled after clipping and 3 and 12 months after endovascular treatment.
                One year postoperatively, 43/41 (surgical/endovascular) patients had good or moderate recovery, 5/4 had severe disability or were in a vegetative state, and 9/7 had died (NS) according to intention to treat. Patients with good clinical recovery did not differ in their neuropsychological test scores. Symptomatic vasospasm (OR 2.47; 95% CI 1.45 to 4.19; P<0.001), poorer Hunt and Hess grade (OR 2.50; 95% CI 1.31 to 4.75; P=0.005), need for permanent shunt (OR 8.90; 95% CI 1.80 to 44.15; P=0.008), and larger size of the aneurysm (OR 1. 22; 95% CI 1.02 to 1.45; P=0.032) independently predicted worsened clinical outcome regardless of the treatment modality. In MRI, superficial brain retraction deficits (P<0.001) and ischemic lesions in the territory of the ruptured aneurysm (P=0.025) were more frequent in the surgical group. Kaplan-Meier analysis (mean+/-SD follow-up 39+/-18 months) revealed equal survival in both treatment groups. No late rebleedings have occurred.
                One-year clinical and neuropsychological outcomes seem comparable after early surgical and endovascular treatment of ruptured intracranial aneurysms. The long-term efficacy of endovascular treatment in preventing rebleeding remains open. The CAESAR Trial aims to assess the outcome of endovascular repair (EVAR) vs surveillance of small abdominal aortic aneurysms (AAA) with maximum diameter of 4.1-5.4 cm on computerised tomography (CT) scan.
                Patients between 50 and 80 years of age, with small AAA, anatomically suitable for EVAR, are randomly allocated to early EVAR or surveillance. The primary outcome measure is survival. Secondary endpoints include: aneurysm-related deaths (defined as any death caused directly or indirectly by rupture or endovascular/open aneurysm repair), AAA rupture, peri-operative or late complications, conversion to open repair, complications associated with delayed treatment including loss of treatment options, AAA growth rates and quality of life. Target recruitment is 740 patients to show that early EVAR is associated with a 15% survival benefit at 54 months.
                Randomization started in September 2004. By the end of April 2005, 86 patients had been enrolled by 10 active European centres. Completion of recruitment is expected for September 2006 and publication of the results in mid 2007. To assess the safety and feasibility of a clinical trial on the effectiveness of acetylsalicylic acid (ASA) in subarachnoid hemorrhage (SAH).
                Several studies have indicated that increased platelet activity might be involved in the pathogenesis of delayed cerebral ischemia (DCI) after SAH.
                Fifty patients who had early surgery (< or =4 days) for a ruptured aneurysm were enrolled in this randomized, double-blind, placebo-controlled trial. Trial medication, consisting of suppositories with 100 mg ASA versus placebo, was started immediately after surgical clipping of the aneurysm and continued for 21 days. End points were functional outcome and quality of life at 4 months, clinical deterioration after operation, development of DCI, hypodense lesion on postoperative CT, and hemorrhagic complications.
                One-third of all patients with aneurysmal SAH were eligible for the trial. Fifteen of 26 patients receiving placebo deteriorated clinically versus 10 of 24 patients receiving ASA; 4 patients in each group deteriorated from DCI. Postoperative hypodensities on CT were observed in 27 patients, distributed equally in both groups. Functional outcome and quality-of-life scores were slightly in favor of patients who had received ASA, but not to a significant degree (p = 0.22). Two patients in the ASA group had an asymptomatic hemorrhagic complication, and one patient in the placebo group had a fatal and another a symptomatic hemorrhagic complication.
                This pilot study shows that a clinical trial of acetylsalicylic acid (ASA) in subarachnoid hemorrhage (SAH) is feasible and probably safe. The effectiveness of ASA on functional outcome and delayed cerebral ischemia has to be studied in a larger trial. One hundred patients with a verified subarachnoid haemorrhage were studied in a double blind, placebo-controlled trial at a single centre to determine the value and relative risks of tranexamic acid (TXA) in the management of ruptured intracranial aneurysms. The incidence of recurrent haemorrhage between active and placebo groups was identical (12%) and the mortality from recurrent haemorrhage was 7% and 5%, respectively. The overall incidence of cerebral infarction before surgery, at discharge and at 6 months follow-up was greater in the TXA group (27%) than in the control group (11%). Post-operative cerebral ischaemia was significantly more frequent in the active, 18 of 29 as compared to 6 of 32 patients, in the placebo group. In a fifth of the patients in whom cerebral blood flow was estimated there was a significant reduction of cerebral blood flow (CBF) on the side of the ruptured aneurysm in the TXA treated group. It is suggested that this may be the cause of the increased incidence of cerebral ischaemia in this group. There was no significant difference in the incidence of cerebral vasospasm, hydrocephalus, visual disturbances and gastrointestinal disturbances. More fatalities were encountered from ischaemia and recurrent haemorrhage in the TXA group but these differences did not reach statistical significance at the 5% level. Given that disability was due to either vasospasm or recurrent haemorrhage than a patient under TXA treatment was significantly more likely to have disability due to vasospasm (p less than 0.04); the reverse was true for the placebo patient (p less than 0.05). From family medical practices 15775 men and women aged 65-80 years were identified and randomized into two groups: one group was invited for ultrasonographic screening for abdominal aortic aneurysm (AAA), and the other acted as age- and sex-matched controls. Of the 7887 invited for screening 5394 (68.4 per cent) accepted. AAA was detected in 218 (4.0 per cent overall and 7.6 per cent of men). Aortic surgery was offered to the screened group if certain criteria were met and no patient died from rupture who was fit for operation and accepted elective treatment. The incidence of rupture was reduced by 55 per cent in men in the group invited for screening, compared with controls. The incidence of rupture in women was low in both groups. Post-haemorrhagic hydrocephalus is assumed to result from obstruction of the cerebrospinal fluid (CSF) pathways by blood clots and subsequent chronic infiltration with collagen. The aim of this work was to evaluate the possibility of preventing permanent shunt dependence by enhancing the endoventricular fibrinolysis by means of an endoventricular streptokinase infusion in babies affected by posthaemorrhagic ventricular dilation. A case-control trial was carried out in 12 neonates affected by intraventricular haemorrhage and subsequent progressive ventriculomegaly. Six of them were treated with 20,000 U/day of streptokinase infused over 96 h through a percutaneous ventricular catheter. Our results show that the percentage of shunted babies was identical in treated and control patients despite the enhancement of endoventricular fibrinolysis obtained in all treated patients. On the basis of our results we do not recommend intraventricular streptokinase infusion for routine use in post-haemorrhagic ventricular dilatation. From 1973 to 1979, 49 patients with internal carotid occlusion were evaluated and treated. Eighteen of 49 (37%) presented with transient ischemic attack/prolonged reversible ischemic neurological deficit, 14 of 49 (29%) presented with mild completed stroke, 13 of 49 (27%) presented with severe completed stroke, and 4 of 49 (8%) were asymptomatic. Surgical treatment consisting of extracranial-intracranial (EC-IC) bypass, internal carotid stump reconstruction and endarterectomy to open the occlusion, contralateral endarterectomy for carotid stenosis opposite the occlusion, and iatrogenic carotid occlusion with EC-IC bypass was carried out on 22 (45%) patients considered at risk for ischemia based on angiographic evidence of poor collateral circulation and potential sources of emboli. Medical treatment consisting of anticoagulants or anti-platelet aggregation agents was used in 27 (55%) patients with good collateral circulation. By 6 weeks after the initiation of treatment, 10 of 49 (20%) reached end points of new strokes and death. By an average of 3 years after treatment began, 30 of 49 (61%) reached the same end points. The results suggest that new ischemic events in the distribution of the occluded carotid artery occur infrequently if the angiographic study shows adequate collateral circulation to the ischemic territory at risk. Surgical revascularization should be reserved for patients with (a) recurrent ischemic events after the diagnosis of carotid occlusion or (b) poor collateral circulation. Decompressive surgery (hemicraniectomy) for life-threatening massive cerebral infarction represents a controversial issue in neurocritical care medicine. We report here the 30-day mortality and 6- and 12-month functional outcomes from the DESTINY trial.
                DESTINY (ISRCTN01258591) is a prospective, multicenter, randomized, controlled, clinical trial based on a sequential design that used mortality after 30 days as the first end point. When this end point was reached, patient enrollment was interrupted as per protocol until recalculation of the projected sample size was performed on the basis of the 6-month outcome (primary end point=modified Rankin Scale score, dichotomized to 0 to 3 versus 4 to 6). All analyses were based on intention to treat.
                A statistically significant reduction in mortality was reached after 32 patients had been included: 15 of 17 (88%) patients randomized to hemicraniectomy versus 7 of 15 (47%) patients randomized to conservative therapy survived after 30 days (P=0.02). After 6 and 12 months, 47% of patients in the surgical arm versus 27% of patients in the conservative treatment arm had a modified Rankin Scale score of 0 to 3 (P=0.23).
                DESTINY showed that hemicraniectomy reduces mortality in large hemispheric stroke. With 32 patients included, the primary end point failed to demonstrate statistical superiority of hemicraniectomy, and the projected sample size was calculated to 188 patients. Despite this failure to meet the primary end point, the steering committee decided to terminate the trial in light of the results of the joint analysis of the 3 European hemicraniectomy trials.
The evidence comes mainly from one large trial. For patients in good clinical condition with ruptured aneurysms of either the anterior or posterior circulation we have firm evidence that, if the aneurysm is considered suitable for both surgical clipping and endovascular treatment, coiling is associated with a better outcome.