Ipsilateral Ischemic Stroke Research Articles

Combined Carotid Endarterectomy and Coronary Artery Bypass: a Still-Feasible Procedure?

To the Editor: The recent article by Randall et al1 is of great interest and involves a large number of patients undergoing carotid artery stent (CAS) and staged myocardial revascularization with a low incidence of periprocedural neurological complication. However, we have some comments and report our own experience. Regarding the AHA guidelines, we do not feel it appropriate to perform carotid/coronary surgery, as Naylor pointed out, with a staged procedure.2 Data on staged procedures taken from his meta-analysis are biased in that the authors do not indicate the number of patients initially enrolled and then submitted to the first procedure (carotid endarterectomy), and the number of patients who leave the study because of neurological or cardiac complications that would contraindicate the programmed staged heart surgery. Furthermore, any procedure, programmed or not, that leaves up to 6 months …

Carotid plaque inflammation detected by 18F-fluorodeoxyglucose-positron emission tomography : Pilot study

Objectives Inflammation is important in both the pathogenesis and outcome of atherosclerosis. Current imaging techniques provide anatomic data but no indication of plaque inflammation. We tested the hypothesis that plaque inflammation could be assessed in vivo by 18FDG-PET and that plaque inflammation could increase the risk of recurrent vascular events and poor response to treatment in a pilot study. Patients and methods Thirteen patients (median age 66.1 years [55–82 years]) with recent carotid territory TIA or ischemic stroke and internal carotid artery (ICA) stenosis ≥50% were studied. Angiography and 18F-fluorodeoxyglucose-positron emission tomography ( 18FDG-PET) imaging were carried out in all patients. Treatment for carotid stenosis in each patient was selected by the attending physician and consisted in medical treatment, endarterectomy or stent placement. During 6 months of follow-up, the specific end points assessed were the occurrence of any stroke, death, or re-stenosis. Results Patients with symptomatic carotid atherosclerosis were imaged using 18FDG-PET. Strong 18FDG uptake (SUV ≥ 2.7) was seen in 11 of 13 (85%) carotid lesions. Among these patients two died during follow-up, 3 had recurrent non-fatal ipsilateral ischemic stroke and 1 patient who had undergone stenting had non-symptomatic re-stenosis in control studies. There was a significant correlation between the 18FDG uptake and degree of ICA stenosis detected by angiography. Conclusion Carotid atherosclerotic plaques contain a variable degree of inflammation which can be assessed in vivo by means of FDG and PET. The prognostic value of this marker is, however, still unclear and needs further study.

30 day results from the SPACE trial of stent-protected angioplasty versus carotid endarterectomy in symptomatic patients: a randomised non-inferiority trial

Carotid endarterectomy is effective in stroke prevention for patients with severe symptomatic carotid-artery stenosis, and carotid-artery stenting has been widely used as alternative treatment. Since equivalence or superiority has not been convincingly shown for either treatment, we aimed to compare the two. 1200 patients with symptomatic carotid-artery stenosis were randomly assigned within 180 days of transient ischaemic attack or moderate stroke (modified Rankin scale score of < or =3) carotid-artery stenting (n=605) or carotid endarterectomy (n=595). The primary endpoint of this hospital-based study was ipsilateral ischaemic stroke or death from time of randomisation to 30 days after the procedure. The non-inferiority margin was defined as less than 2.5% on the basis of an expected event rate of 5%. Analyses were on an intention-to-treat basis. This trial is registered at Current Controlled Trials with the international standard randomised controlled trial number ISRCTN57874028. 1183 patients were included in the analysis. The rate of death or ipsilateral ischaemic stroke from randomisation to 30 days after the procedure was 6.84% with carotid-artery stenting and 6.34% with carotid endarterectomy (absolute difference 0.51%, 90% CI -1.89% to 2.91%). The one-sided p value for non-inferiority is 0.09. SPACE failed to prove non-inferiority of carotid-artery stenting compared with carotid endarterectomy for the periprocedural complication rate. The results of this trial do not justify the widespread use in the short-term of carotid-artery stenting for treatment of carotid-artery stenoses. Results at 6-24 months are awaited.

Effect of Nonoptimal Imaging on the Relationship Between the Measured Degree of Symptomatic Carotid Stenosis and Risk of Ischemic Stroke

Some recent studies of noninvasive carotid imaging have identified high rates of inappropriate decision-making about endarterectomy compared with conventional arterial angiography (CAA), but there is substantial inconsistency across the published literature. CAA is usually regarded as the gold standard for carotid imaging, partly because the degree of angiographic stenosis is a powerful predictor of ischemic stroke and hence of benefit from endarterectomy. However, there are very few published data on the extent to which predictive power varies with type of CAA or the number and quality of views of the stenosis obtained. We analyzed measurements of stenosis made by 2 independent observers on 967 consecutive patients randomized to medial treatment alone in the European Carotid Surgery Trial (ECST). We determined prediction of 3-year risk of ipsilateral ischemic stroke (as a hazard ratio from a Cox model and as the area under a receiver operating characteristic curve [AUC]) in relation to the technique of angiography, the number and quality of views of the stenosis, and the use of 2 independent measurements. Using 2 independent measurements of stenosis increased predictive power slightly, but the effect was much smaller than that attributable to the type of CAA and the number of views of the stenosis. Prognostic value was greater in patients who had selective carotid injection CAA and at least biplane views (AUC, 0.75; 0.68 to 0.82) than in patients with only a single view or aortic arch injection CAA (AUC, 0.65; 0.56 to 0.73; P=0.03). The dependence of the prognostic value of CAA on the type of angiography and the number of views of the stenosis obtained has implications for the future development and validation of noninvasive methods of carotid imaging.

Major Ongoing Stroke Trials

Major Ongoing Stroke Trials

無症候性内頸動脈狭窄 無症候性頸部内頸動脈狭窄症に対するステント留置術

We have performed carotid artery stenting (CAS) for 327 patients with ICA stenosis in our institutes using various embolic protection devices since 1997. After establishment of embolic protection methods in 1999, we have performed CAS for 114 asymptomatic carotid stenosis of more than 60%, according to the criteria of ACAS trial. In this paper, we report our initial results (perioperative complication, morbidity/mortality at 30 days after CAS, changes in stenosis ratio), rate of re-stenosis, and midterm results in cases followed more than 3 years after CAS. The mean preoperative stenosis ratio, 75.6%, remarkably decreased to 5.6% after CAS. The morbidity/motality rate at 30 days after CAS was 0.8% (1/114 cases). In 22 cases, followed up more than 3 years after CAS, no ipsilateral ischemic stroke was encountered. CAS for asymptomatic carotid stenosis is an effective and safe treatment to alleviate stenosis and prevent future ischemic stroke as well as carotid endarterectomy (CEA). Randomized controlled trials, based on the natural history of carotid stenosis, are needed in the near future to establish the indication of CAS for asymptomatic carotid stenosis.

Major Ongoing Stroke Trials

Major Ongoing Stroke Trials

頚部内頚動脈狭窄症に対するステント留置術―治療手技での工夫と治療成績―

We have performed CAS for 239 patients with ICA stenosis in our institute using various protection devices since 1997. In this paper, we report our initial results (perioperative complication, morbidity/mortality 30 days after the procedure, change of stenosis ratio), rate of re-stenosis, and midterm results in the cases more than 3 years after CAS. The mean preoperative stenosis ratio, 79.6%, remarkably decreased to 6.2% after CAS. The morbidity/mortality rate at 30 days after CAS was 2.1% (5/239 cases). Five of 179 cases showed restenosis 6 months after CAS (3.2%). In 4 of these cases, in-stent PTA was performed. None of the cases showed new neurological deficits. In 62 cases, followed up more than 3 years after CAS, no ipsilateral ischemic stroke was encountered. Carotid artery stenting (CAS) for internal carotid artery (ICA) stenosis is an effective and safe treatment to alleviate stenosis and prevent future ischemic stroke as well as carotid endarterectomy (CEA). However, it is necessary to learn several technical methods and optional procedures for successful CAS in all carotid stenoses.

Systematic review of randomized controlled trials of patch angioplasty versus primary closure and different types of patch materials during carotid endarterectomy

Patch angioplasty during carotid endarterectomy (CEA) may reduce the risk for perioperative or late carotid artery recurrent stenosis and subsequent ischemic stroke. We performed a systematic review of randomized controlled trials to assess the effect of routine or selective carotid patch angioplasty compared with CEA with primary closure, and the effect of different materials used for carotid patch angioplasty. Randomized trials were included if they compared carotid patch angioplasty with primary closure in any patients undergoing CEA or use of one type of carotid patch with another. Thirteen eligible randomized trials were identified. Seven trials involving 1281 operations compared primary closure with routine patch closure, and 8 trials with 1480 operations compared different patch materials (2 studies compared both). Patch angioplasty was associated with a reduction in risk for stroke of any type (P = .004), ipsilateral stroke (P = .001), and stroke or death during both the perioperative period (P = .007) and long-term follow-up (P = .004). Patching was also associated with reduced risk for perioperative arterial occlusion (P = .0001) and decreased recurrent stenosis during long-term follow-up (P < .0001). Seven trials that compared different patch types showed no difference in the risk for stroke, death, or arterial recurrent stenosis either perioperatively or at 1-year follow-up. One study of 180 patients (200 arteries) compared collagen-impregnated Dacron (Hemashield) patches with polytetrafluoroethylene patches. There was a significant increase in risk for stroke (P = .02), combined stroke and transient ischemic attack (P = .03), and recurrent stenosis (P = .01) at 30 days, and an increased risk for late recurrent stenosis greater than 50% (P < .001) associated with Dacron compared with polytetrafluoroethylene. Carotid patch angioplasty decreases the risk for perioperative death or stroke, and long-term risk for ipsilateral ischemic stroke. More data are required to establish differences between various patch materials.

Sex Difference in the Effect of Time From Symptoms to Surgery on Benefit From Carotid Endarterectomy for Transient Ischemic Attack and Nondisabling Stroke

Early studies showed that carotid endarterectomy (CEA) carried a high risk if performed within days after a large ischemic stroke. Therefore, many surgeons delay CEA for 4 to 6 weeks after any stroke. To determine the effect of delay to CEA on operative risk and benefit, we pooled data from the North American Symptomatic Carotid Endarterectomy Trial and the European Carotid Surgery Trial. Risk of ipsilateral ischemic stroke in the medical group, operative risk of stroke and death, and overall benefit from surgery were determined in relation to the time from the last symptomatic event to randomization. Operative risk of stroke and death was also determined in relation to the time to surgery. Analyses were stratified by sex and type of presenting event. The 30-day perioperative risk of stroke and death was unrelated to the time since the last symptomatic event and was not increased in patients operated <2 weeks after nondisabling stroke. In contrast, the risk of ipsilateral ischemic stroke in the medical group fell rapidly with time since event (P<0.001), as did the absolute benefit from surgery (P=0.001). This decline in benefit with time was unrelated to the type of presenting event but was more pronounced in women than men (difference P<0.001). Benefit in women was confined to those randomized <2 weeks after their last event, irrespective of severity of stenosis. CEA can be performed safely within 2 weeks of nondisabling ischemic stroke. Benefit from endarterectomy declines rapidly with increasing delay, particularly in women.

Major Ongoing Stroke Trials

Major Ongoing Stroke Trials

Recurrent stroke in patients with symptomatic carotid artery occlusion is associated with high-volume flow to the brain and increased collateral circulation.

To investigate whether the risk of recurrent ipsilateral ischemic stroke in patients with symptomatic carotid artery occlusion (CAO) is related to (1) volume flow in the contralateral internal carotid artery (ICA), basilar artery (BA), and middle cerebral arteries (MCAs), and (2) intracranial collateral flow to the symptomatic side, measured in the first 6 months after the qualifying symptoms occurred. We prospectively studied 112 patients with symptomatic CAO. Quantitative volume flow was measured with magnetic resonance angiography (MRA) and collateral flow via the circle of Willis with MRA, via the ophthalmic artery (OA) with transcranial Doppler sonography, and via leptomeningeal anastomoses with conventional angiography. During 49+/-14 months of follow-up (mean+/-SD), 7 patients had recurrent ipsilateral ischemic stroke. Compared with patients without recurrent stroke, these patients had significantly higher total flow to the brain, ie, ICA+BA flow (mean 536 mL/min versus 410 mL/min; P<0.05), and significantly higher contralateral ICA flow (355 mL/min versus 209 mL/min; P<0.001), whereas BA and MCA flow showed no significant differences. Also, they more often had Willisian collateral flow (P<0.05), mainly caused by increased collateral flow via the posterior communicating artery (PCoA; 71% versus 28%; P<0.05), whereas collateral flow via the OA and leptomeningeal anastomoses did not differ significantly. Recurrent ipsilateral ischemic stroke in patients with symptomatic CAO is associated with high volume flow to the brain and increased collateral PCoA flow.

Endarterectomy for symptomatic carotid stenosis in relation to clinical subgroups and timing of surgery

Carotid endarterectomy reduces the risk of stroke in patients with recently symptomatic stenosis. Benefit depends on the degree of stenosis, and we aimed to see whether it might also depend on other clinical and angiographic characteristics, and on the timing of surgery. We analysed pooled data from the European Carotid Surgery Trial and North American Symptomatic Carotid Endarterectomy Trial. The risk of ipsilateral ischaemic stroke for patients on medical treatment, the perioperative risk of stroke and death, and the overall benefit from surgery were determined in relation to seven predefined and seven post hoc subgroups. 5893 patients with 33000 patient-years of follow-up were analysed. Sex (p=0.003), age (p=0.03), and time from the last symptomatic event to randomisation (p=0.009) modified the effectiveness of surgery. Benefit from surgery was greatest in men, patients aged 75 years or older, and those randomised within 2 weeks after their last ischaemic event, and fell rapidly with increasing delay. For patients with 50% or higher stenosis, the number of patients needed to undergo surgery (ie, number needed to treat) to prevent one ipsilateral stroke in 5 years was nine for men versus 36 for women, five for age 75 years or older versus 18 for younger than 65 years, and five for those randomised within 2 weeks after their last ischaemic event, versus 125 for patients randomised after more than 12 weeks. These results were consistent across the individual trials. Benefit from endarterectomy depends not only on the degree of carotid stenosis, but also on several other clinical characteristics such as delay to surgery after the presenting event. Ideally, the procedure should be done within 2 weeks of the patient's last symptoms.

Major Ongoing Stroke Trials

Major Ongoing Stroke Trials

Outcome of carotid endarterectomy in African Americans: is race a factor?

African American patients have been underrepresented in large-scale trials of carotid endarterectomy (CEA). Thus the role of CEA in the treatment of extracranial carotid artery occlusive disease in black patients remains unclear. We undertook this study to determine the effect of black race on early and late outcome of CEA. A retrospective review was performed of records for patients who underwent CEA from 1990 to 1999. Data on demographics, operative indications, hospital course, and long-term follow-up were obtained for each patient. Patients were stratified by race for comparison of perioperative course and late outcome. Risk factors were compared using chi(2) methods, and life table analysis was performed with Kaplan-Meier survival plots. One thousand forty-five CEA procedures were performed during the study period, 133 (13%) in black patients and 912 (87%) in white patients. Demographic risk factors were similar in both groups, except for hypertension (P =.003), diabetes (P <.001), and renal insufficiency (P =.03), which were more prevalent in blacks. Just over half of patients had symptoms at presentation, with equal racial distribution. The perioperative stroke and death rate was 3.3% (blacks, 5.3%; whites, 3.1%; P =.19). The 8-year actuarial ipsilateral stroke rate was 7% in patients without symptoms and 8% in patients with symptoms, with no racial variation. There was, however, a racial difference in the long-term "all strokes" rate (P =.002), regardless of vascular territory. This difference was largely due to the high late stroke rate in black patients with symptoms at presentation. A Cox proportional hazards analysis showed that only black race was a significant predictor of any stroke. CEA can be accomplished with acceptable morbidity and mortality in black patients with an expectation of similar protection from ipsilateral ischemic stroke as in white patients. Black patients, however, have a higher incidence of all strokes at long-term follow-up due to the higher risk of stroke in patients with symptoms of carotid bifurcation disease.

The Carotid Occlusion Surgery Study

The St. Louis Carotid Occlusion Study demonstrated that ipsilateral increased O2 extraction fraction (OEF) (Stage II hemodynamic failure) measured by positron emission tomography (PET) is a powerful independent risk factor for subsequent stroke in patients with symptomatic complete carotid artery (CA) occlusion. The ipsilateral ischemic stroke rate at 2 years has been shown to be 5.3% in 42 patients with normal OEF and 26.5% in 39 patients with increased OEF (p = 0.004). In patients in whom hemispheric symptoms developed within 120 days, the 2-year ipsilateral stroke rates were 12% in 27 patients with normal OEF and 50% in 18 patients with increased OEF. Previous PET studies have demonstrated that anastomosis of the superficial temporal artery (STA) to a middle cerebral artery (MCA) cortical branch can restore OEF to normal. The authors discuss the undertaking of a study that will test the hypothesis that STA-MCA anastomosis, when combined with the best medical therapy, can reduce ipsilateral ischemic stroke by 40% at 2 years in patients with symptomatic internal CA occlusion and Stage II hemodynamic failure occurring within 120 days after surgery. Only patients with increased OEF distal to a symptomatic occluded CA will be randomized to surgery or medical treatment. The primary endpoint will be all strokes and death occurring between randomization and the 30-day postoperative cut off (with an equivalent period in the nonsurgical group), as well as subsequent ipsilateral ischemic stroke developing within 2 years. It is estimated that 186 patients will be required in each group. Assuming that 40% of PET scans will demonstrate increased OEF, this will require enrolling 930 clinically eligible individuals.

Analysis of pooled data from the randomised controlled trials of endarterectomy for symptomatic carotid stenosis

Endarterectomy reduces risk of stroke in certain patients with recently symptomatic internal carotid stenosis. However, investigators have made different recommendations about the degree of stenosis above which surgery is effective, partly because of differences between trials in the methods of measurement of stenosis. To accurately assess the overall effect of surgery, and to increase power for secondary analyses, we pooled trial data and reassessed carotid angiograms. We pooled data from the European Carotid Surgery Trial (ECST), North American Symptomatic Carotid Endarterectomy Trial, and Veterans Affairs trial 309 from the original electronic data files. Outcome events were re-defined, if necessary, to achieve comparability. Pre-randomisation carotid angiograms from ECST were re-measured by the method used in the other two trials. Risks of main outcomes in both treatment groups and effects of surgery did not differ between trials. Data for 6092 patients, with 35000 patient-years of follow-up, were therefore pooled. Surgery increased the 5-year risk of ipsilateral ischaemic stroke in patients with less than 30% stenosis (n=1746, absolute risk reduction -2.2%, p=0.05), had no effect in patients with 30-49% stenosis (1429, 3.2%, p=0.6), was of marginal benefit in those with 50-69% stenosis (1549, 4.6%, p=0.04), and was highly beneficial in those with 70% stenosis or greater without near-occlusion (1095, 16.0%, p<0.001). There was a trend towards benefit from surgery in patients with near-occlusion at 2 years' follow-up (262, 5.6%, p=0.19), but no benefit at 5 years (-1.7%, p=0.9). Re-analysis of the trials with the same measurements and definitions yielded highly consistent results. Surgery is of some benefit for patients with 50-69% symptomatic stenosis, and highly beneficial for those with 70% symptomatic stenosis or greater but without near-occlusion. Benefit in patients with carotid near-occlusion is marginal in the short-term and uncertain in the long-term.

Long-term durability of carotid endarterectomy for symptomatic stenosis and risk factors for late postoperative stroke.

Carotid endarterectomy (CEA) reduces the risk of stroke ipsilateral to recently symptomatic severe carotid stenosis. Other techniques such as percutaneous transluminal angioplasty with stenting are currently being compared with CEA. Thus far, case series and several small, randomized, controlled trials of CEA versus percutaneous transluminal angioplasty (with and without stenting) have focused primarily on the 30-day procedural risks of stroke and death. However, long-term durability is also important. To determine the long-term risk of stroke after CEA and to identify risk factors, we studied patients in the European Carotid Study Trial (ECST), the largest published cohort with long-term follow-up by physicians after CEA. Risks of ipsilateral carotid territory ischemic stroke were calculated by Kaplan-Meier analysis starting on the 30th day after CEA in 1728 patients who underwent trial surgery. Risk factors were determined by Cox regression. For comparison, we also determined the "background" risk of stroke on medical treatment in the ECST in the territory of 558 previously asymptomatic contralateral carotid arteries with <30% angiographic stenosis (ECST method) at randomization. The risks of disabling ipsilateral ischemic stroke and any ipsilateral ischemic stroke were constant after CEA, reaching 4.4% [95% confidence interval (CI), 3.0 to 5.8] and 9.7% (95% CI, 7.6 to 11.7), respectively, by 10 years. The equivalent ischemic stroke risks distal to contralateral <30% asymptomatic carotid stenoses were 1.9% (95% CI, 0.8 to 3.2) and 4.5% (95% CI, 1.5 to 7.4). Presentation with cerebral symptoms, diabetes, elevated systolic blood pressure, smoking, male sex, increasing age, and a lesser severity of preoperative stenosis were associated with an increased risk of late stroke after CEA, but plaque morphology and patch grafting were not. Although the risk of late ipsilateral ischemic stroke after CEA for symptomatic stenosis is approximately double the background risk in the territory of <30% asymptomatic stenosis, it is still only approximately 1% per year and remains low for at least 10 years after CEA. This is the standard against which alternative treatments should be judged. Several risk factors may be useful in identifying patients at particularly high risk of late postoperative stroke.

Major Ongoing Stroke Trials

Major Ongoing Stroke Trials

Alamowitch S, Eliasziw M, Algra A, et al. Risk, causes, and prevention of ischemic stroke in elderly patients with symptomatic internal-carotid-artery stenosis.

Alamowitch S, Eliasziw M, Algra A, et al. Risk, causes, and prevention of ischemic stroke in elderly patients with symptomatic internal-carotid-artery stenosis. Lancet 2001;357:1154–60. Alamowitch et al. studied patients from the North American Symptomatic Carotid Endarterectomy Trial (NASCET) with symptomatic internal carotid artery (ICA) stenosis. They stratified by age and compared outcomes of patients treated with carotid endarterectomy to best medical therapy. Patients were classified into three age groups: 75 years or older, 65 to 74 years, and younger than 65 years. The first group was considered elderly. At baseline these patients were less likely than younger patients to have atherosclerotic risk factors and least likely to have severe ICA stenosis. Among surgically treated patients, the elderly group had the lowest risk of ipsilateral stroke, regardless of the degree of ICA stenosis. However, they had the highest risk of stroke with medical management, which depended on the degree of ICA stenosis (24.9% risk of stroke for 50%–69% stenosis; 36.5% risk of stroke for 70%–99% stenosis). Because elderly patients had the highest risk with medical management, the absolute risk reduction with surgical management was greatest (28.9%, P < 0.0001). In addition, among patients with 50% to 69% stenosis, reduction in risk was significant only for the oldest age group (17.3%, P = 0.0005). No significant benefit to surgical management was seen in patients with less than 50% stenosis in any age category. The greatest benefit of surgery in the elderly, compared with the younger patients, resulted from having a combination of the highest risk of ipsilateral ischemic stroke if managed medically and the lowest surgical risk, presumably because of their lower number of baseline atherosclerotic risk factors. These data should help guide choice of therapy for elderly patients and symptomatic ICA stenosis.