To investigate the natural history of unruptured aneurysms and predictive risk factors determining subsequent rupture, the authors followed 142 patients with 181 unruptured aneurysms until death or subarachnoid hemorrhage intervened, or for at least 10 years after the unruptured aneurysm was diagnosed. Six patients had a symptomatic aneurysm, five had an incidentally discovered aneurysm, and 131 had multiple aneurysms, of which the ruptured lesion was clipped at the beginning of the follow-up study. The median follow-up time was 13.9 years (range 0.8 to 30.0 years). During 1944 patient-years of follow-up study there were 27 first episodes of hemorrhage from a previously unruptured aneurysm, giving an average annual rupture incidence of 1.4%. Fourteen of these bleeding episodes were fatal. The cumulative rate of bleeding was 10% at 10 years, 26% at 20 years, and 32% at 30 years after the diagnosis. The only predictor for the rupture was the size of the aneurysm (p = 0.036). However, in patients with multiple aneurysms (the main subgroup) the only variable that tended to predict rupture was the age of the patient: risk of rupture was inversely associated with age (p = 0.080). The median diameter of the aneurysms was 4 mm at the beginning of the follow-up period, both in those with and those without a later hemorrhage. During the angiographic monitoring period, a ruptured aneurysm significantly (p < 0.001) increased in size in 17 patients with hemorrhage but aneurysms did not increase significantly in 14 patients without hemorrhage. In addition, a new aneurysm was found in six of 31 patients. The authors conclude that an unruptured aneurysm should be operated on, irrespective of its size, if it is technically possible and the patient's age and concurrent diseases are not contraindications to surgery.

Background and Purpose-We sought to investigate factors determining growth rate of unruptured intracranial aneurysms as well as formation of new (de novo) aneurysms in patients from a time period when unruptured aneurysms were not treated surgically. Methods-Eighty-seven patients (79 had ruptured aneurysms clipped at start of follow-up) with 111 unruptured aneurysms as well as an additional 7 patients (2 with and 5 without unruptured aneurysms) who developed new aneurysms were followed from the 1950s to the 1970s until death or subarachnoid hemorrhage or until the last contact. Patients' cerebral arteries were examined later either with conventional (control) angiography (nϭ38) and/or, for those alive during 1996 -1998, with 3-dimensional CT angiography (nϭ57). In addition, 10 patients were studied at neuropathological autopsy. Results-MeanϮSD duration of follow-up was 18.9Ϯ9.4 years (range, 1.2 to 38.9 years). Unruptured aneurysms increased in size Ն1 mm in 39 of the 87 patients (45%) and Ն3 mm in 31 (36%

Cigarette smoking, size of the unruptured intracranial aneurysm, and age, inversely, are important factors determining risk for subsequent aneurysm rupture. The authors conclude that such unruptured aneurysms should be surgically treated regardless of their size and of a patient's smoking status, especially in young and middle-aged adults, if this is technically possible and if the patient's concurrent diseases are not contraindications. Cessation of smoking may also be a good alternative to surgery in older patients with small-sized aneurysms.

SummaryBackgroundStents are an alternative treatment to carotid endarterectomy for symptomatic carotid stenosis, but previous trials have not established equivalent safety and efficacy. We compared the safety of carotid artery stenting with that of carotid endarterectomy.MethodsThe International Carotid Stenting Study (ICSS) is a multicentre, international, randomised controlled trial with blinded adjudication of outcomes. Patients with recently symptomatic carotid artery stenosis were randomly assigned in a 1:1 ratio to receive carotid artery stenting or carotid endarterectomy. Randomisation was by telephone call or fax to a central computerised service and was stratified by centre with minimisation for sex, age, contralateral occlusion, and side of the randomised artery. Patients and investigators were not masked to treatment assignment. Patients were followed up by independent clinicians not directly involved in delivering the randomised treatment. The primary outcome measure of the trial is the 3-year rate of fatal or disabling stroke in any territory, which has not been analysed yet. The main outcome measure for the interim safety analysis was the 120-day rate of stroke, death, or procedural myocardial infarction. Analysis was by intention to treat (ITT). This study is registered, number ISRCTN25337470.FindingsThe trial enrolled 1713 patients (stenting group, n=855; endarterectomy group, n=858). Two patients in the stenting group and one in the endarterectomy group withdrew immediately after randomisation, and were not included in the ITT analysis. Between randomisation and 120 days, there were 34 (Kaplan-Meier estimate 4·0%) events of disabling stroke or death in the stenting group compared with 27 (3·2%) events in the endarterectomy group (hazard ratio [HR] 1·28, 95% CI 0·77–2·11). The incidence of stroke, death, or procedural myocardial infarction was 8·5% in the stenting group compared with 5·2% in the endarterectomy group (72 vs 44 events; HR 1·69, 1·16–2·45, p=0·006). Risks of any stroke (65 vs 35 events; HR 1·92, 1·27–2·89) and all-cause death (19 vs seven events; HR 2·76, 1·16–6·56) were higher in the stenting group than in the endarterectomy group. Three procedural myocardial infarctions were recorded in the stenting group, all of which were fatal, compared with four, all non-fatal, in the endarterectomy group. There was one event of cranial nerve palsy in the stenting group compared with 45 in the endarterectomy group. There were also fewer haematomas of any severity in the stenting group than in the endarterectomy group (31 vs 50 events; p=0·0197).InterpretationCompletion of long-term follow-up is needed to establish the efficacy of carotid artery stenting compared with endarterectomy. In the meantime, carotid endarterectomy should remain the treatment of choice for patients suitable for surgery.FundingMedical Research Council, the Stroke Association, Sanofi-Synthélabo, European Union.

Object. The authors conducted a study to investigate the long-term natural history of unruptured intracranial aneurysms and the predictive risk factors determining subsequent rupture in a patient population in which surgical selection of cases was not performed. Methods. One hundred forty-two patients with 181 unruptured aneurysms were followed from the 1950s until death or the occurrence of subarachnoid hemorrhage or until the years 1997 to 1998. The annual and cumulative incidence of aneurysm rupture as well as several potential risk factors predictive of rupture were studied using life-table analyses and Cox's proportional hazards regression models including time-dependent covariates. The median follow-up time was 19.7 years (range 0.8–38.9 years). During 2575 person-years of follow up, there were 33 first-time episodes of hemorrhage from previously unruptured aneurysms, for an average annual incidence of 1.3%. In 17 patients, hemorrhage led to death. The cumulative rate of bleeding was 10.5% at 10 years, 23% at 20 years, and 30.3% at 30 years after diagnosis. The diameter of the unruptured aneurysm (relative risk [RR] 1.11 per mm in diameter, 95% confidence interval [CI] 1–1.23, p = 0.05) and patient age at diagnosis inversely (RR 0.97 per year, 95% CI 0.93–1, p = 0.05) were significant independent predictors for a subsequent aneurysm rupture after adjustment for sex, hypertension, and aneurysm group. Active smoking status at the time of diagnosis was a significant risk factor for aneurysm rupture (RR 1.46, 95% CI 1.04–2.06, p = 0.033) after adjustment for size of the aneurysm, patient age, sex, presence of hypertension, and aneurysm group. Active smoking status as a time-dependent covariate was an even more significant risk factor for aneurysm rupture (adjusted RR 3.04, 95% CI 1.21–7.66, p = 0.02). Conclusions. Cigarette smoking, size of the unruptured intracranial aneurysm, and age, inversely, are important factors determining risk for subsequent aneurysm rupture. The authors conclude that such unruptured aneurysms should be surgically treated regardless of their size and of a patient's smoking status, especially in young and middle-aged adults, if this is technically possible and if the patient's concurrent diseases are not contraindications. Cessation of smoking may also be a good alternative to surgery in older patients with small-sized aneurysms.