Long-term clinical and angiographic outcomes in symptomatic patients with 70% to 99% carotid artery stenosis.

BACKGROUND AND PURPOSE: In 1991, the North American Symptomatic Carotid Endarterectomy Trial (NASCET) reported the benefit of carotid endarterectomy for 659 patients with 70% to 99% stenosis. Follow-up continued until 1997. METHODS: The present study examined the risks and causes of ipsilateral stroke in the randomized groups and in those who had delayed endarterectomy or continued on medical therapy and also examined the evolution of carotid disease on follow-up imaging. RESULTS: By on-treatment (efficacy) analysis, the risk of any ipsilateral stroke at 3 years was 28.3% for medically randomized and 8.9% for surgically randomized patients (19.4% absolute risk reduction, P:<0.001). For combined disabling or fatal ipsilateral stroke, the risks were 14.0% and 3.4%, respectively (10. 6% absolute risk reduction). In medical patients, >80% of the first strokes at 3 years were of large-artery origin. After February 1991, 116 suitable medical patients underwent endarterectomy within 6 months, and 115 continued on medical therapy. The 3-year risk of any ipsilateral stroke in the groups of 116 and 115 patients was 7.9% and 15.0%, respectively (7.1% absolute risk reduction). During follow-up, 81 patients had angiograms comparable to the baseline images. Progression by >/=10% occurred in 7 patients; regression, in 8; no change, in 39; and occlusion, in 27. By use of both angiography and ultrasound, 63 (25.5%) of the 247 medically treated patients progressed to occlusion, of whom 31.7% had an ipsilateral stroke before or on the day of occlusion. CONCLUSIONS: Endarterectomy for patients with 70% to 99% stenosis and recent symptoms was efficacious in the long term. Compared with patients who continued on medical therapy, medical patients with delayed endarterectomy experienced a moderate benefit. Medically treated patients experienced a high risk of occlusion.

Do the facts and figures warrant a 10-fold increase in the performance of carotid endarterectomy on asymptomatic patients?

The detailed results of the Asymptomatic Carotid Atherosclerosis Study (ACAS) have been published. Electrifying reports in the media suggested that 53% fewer strokes would occur if individuals with 60% or greater stenosis were submitted to endarterectomy. The burning question is whether the evidence from this trial, and those preceding it, is sufficiently compelling to persuade any or all individuals with carotid stenosis, but free of any hemisphere and retinal symptoms, to have carotid endarterectomy. Based on a variety of population samplings, it is reasonable to estimate that approximately two million people are living in North America and Europe with asymptomatic lesions comparable with those studied in the ACAS.

Dandruff: a condition characterized by decreased levels of intercellular lipids in scalp stratum corneum and impaired barrier function.

Dandruff is a major problem, yet little is known about the underlying mechanism and subsequent biochemical changes occurring in the scalp skin that lead to its manifestation. The characteristic flaking and scaling of the scalp experienced by dandruff sufferers suggests, similar to the changes classically seen in xerosis, that the desquamation process is impaired. We initiated studies to quantify the biochemical nature of the stratum corneum in the scalp of healthy individuals and dandruff sufferers. Total amounts and relative ratios of stratum corneum lipids species were analysed in scalp stratum corneum samples collected during studies conducted in the UK and Thailand in order to examine ethnic differences. In both populations, dandruff was associated with a dramatic decrease in free lipid levels, with significant decreases in ceramides, fatty acids, and cholesterol. Detailed sub-analysis of the major ceramide species within the total ceramide fraction revealed a decrease in ceramide 1 and increased proportions of ceramide 6i and 6ii. In a separate study, we demonstrated that dandruff sufferers show both an elevated blood flow and an increased reported incidence of itch in response to histamine topically applied to the scalp compared with no-dandruff controls. Taken together these two studies indicate that the quality and resilience of the epidermal water barrier is impaired in the scalp of dandruff sufferers. We propose that the perturbed barrier leaves dandruff sufferers more prone to the adverse effects of microbial and fungal toxins, and environmental pollutants, thus perpetuating their impaired barrier.

Status of carotid endarterectomy.

The randomized clinical trial has been brought to bear on the indications and the search for benefit for the surgical procedure of carotid endarterectomy. Progress has been made and some answers are available. It is not too optimistic to state that in a few years time, we will be able to state with some degree of finality, which patients with symptomatic disease will benefit from carotid endarterectomy, which ones will be better treated with medical therapy alone, and whether or not there is a group of patients, despite being asymptomatic, who should be advised to have this procedure.

Appropriate use of carotid endarterectomy.

When stroke-threatening symptoms derive from the extracranial portion of a carotid artery, endarterectomy becomes a consideration. The available evidence indicates clear benefit for patients with a severe symptomatic stenosis. For asymptomatic carotid disease, the risk of a surgical complication may contraindicate the procedure.

Update on carotid endarterectomy.

Progress in therapeutic decision-making for patients with carotid artery disease has come from evaluations made by several major randomized clinical trials. For patients who are symptomatic and have arteriographically proven stenoses of 70% or more, endarterectomy is clearly established as the treatment of choice. Symptomatic patients with stenoses of less than 70% remain the subject of ongoing study. Asymptomatic patients are at low risk of stroke save for those with the highest (80% to 90%) degrees of stenosis, and even for these subjects the annual stroke rate is close to the operative risk. Four trials have been reported but the practicing physician is still without clear guidelines. The appropriateness of endarterectomy remains unsettled for any group of patients with narrowing of the carotid artery in the absence of symptoms. The decision to apply endarterectomy to symptomatic and to asymptomatic patients must attend to not only the prognostic importance of the degree of stenosis, but also to the vascular risk profile of the individual patient.

Endarterectomy for carotid stenosis: new approaches in patient selection.

Results of randomized trials on carotid endarterectomy make it mandatory that therapeutic decisions for patients with carotid stenosis consider the degree of stenosis, presence of symptoms, skill of surgeon and time since the last ischemic event. Patients with severe (>70% by angiogram) stenosis should receive carotid endarterectomy, provided the operative risk is <6% and symptoms have recurred within 6 months. With moderate stenosis (50--69% by angiogram), and with similar low operative risk and time limit, males with hemispheric, nondisabling stroke and appropriate CT lesion will benefit from carotid endarterectomy. Patients with TIA only, retinal symptoms alone and who are women are not going to benefit in this range of stenosis. Particularly at risk with medical care alone are symptomatic patients with coexistent intracranial stenosis, widespread white-matter lesions, intraluminal thrombi, contralateral occlusion and absence of good collateral circulation. The same high-risk patients, enjoy good long-term results from endarterectomy. Lacunar syndromes at presentation respond to endarterectomy, but with less benefit. Symptomatic patients do as well, regardless of age, provided patients with serious cardiac disorders and with organ failure are avoided. Serious doubt exists about indications for endarterectomy in asymptomatic subjects. Even if the upper limit of 3% perioperative risk is exceeded (and in large institutional databases and other studies, it usually is), the risk of large-artery strokes from the asymptomatic lesion is only slightly above the risk facing these subjects from lacunar and cardioembolic stroke. To prevent 1 large-artery stroke in 5 years in asymptomatic subjects requires that 111 subjects be submitted to endarterectomy.

Drugs and surgery in the prevention of ischemic stroke.

Randomized clinical trials have proved that warfarin therapy decreases the risk of stroke in patients with nonvalvular atrial fibrillation and in those who have had a myocardial infarction. In patients who are not candidates for long-term anticoagulant therapy, aspirin is beneficial, but the reduction in risk is smaller with aspirin than with warfarin. In patients with cerebral ischemic symptoms of noncardiac origin, aspirin and ticlopidine reduce the risk of stroke, but the benefit is modest. Given alone, neither dipyridamole nor sulfinpyrazone prevents stroke. The question remains whether either of these drugs plus aspirin is better than aspirin alone. The optimal dose of aspirin for stroke prevention has not been established. Carotid endarterectomy reduces the risk of stroke in symptomatic patients with at least 70 percent stenosis, as determined by arteriography. Current trials are addressing the question of whether endarterectomy is beneficial for patients with moderate degrees of carotid stenosis. The benefit of endarterectomy for patients with asymptomatic carotid lesions remains unclear.

The dilemma of surgical treatment for patients with asymptomatic carotid disease.

Several case series have suggested that endarterectomy is beneficial in asymptomatic carotid artery disease. Four randomized trials have been done in this area, the most recent of which is the Asymptomatic Carotid Atherosclerosis Study (ACAS). Results of the first three trials were negative, and ACAS produced a tantalizing, statistically significant finding that does not translate into clinical importance. Disabling strokes have not been reduced by surgical therapy, and the benefit for women has not been shown. It is unclear from this study whether persons with the greatest stenosis and the highest vascular risk profiles are appropriate candidates for endarterectomy. In patients in whom carotid artery disease is incidentally discovered, the benefits of the prophylactic addition of carotid endarterectomy to coronary bypass grafting or other major surgical procedure in patients are still unknown. Excellent surgical skill is of paramount importance for the future use of this procedure. Mass population screening to detect asymptomatic carotid disease will only be justified when and if future studies identify patients in whom the risk for disabling stroke after the procedure is clearly reduced.

Carotid endarterectomy: emerging indications.

Several randomized trials have recently reported on the benefit of carotid endarterectomy for symptomatic or asymptomatic patients. A positive benefit has been found for symptomatic patients with > or = 70% stenosis measured by angiogram with a particular formula and performed with high surgical skill. Symptomatic patients with < 70% stenosis continue to be randomized and followed. The answer for this group is expected in the next two years. The randomized trials of asymptomatic patients have not established the benefit for carotid endarterectomy clearly. The most recent trial shows the absolute risk reduction at 5 years is only 5.9% or less than 1.5% risk reduction per year. A fifth trial continues in Europe.

Risk, causes, and prevention of ischaemic stroke in elderly patients with symptomatic internal-carotid-artery stenosis.

BACKGROUND: Carotid endarterectomy benefits patients with symptomatic stenosis of 70-99% in the internal carotid artery, with smaller benefit for 50-69% stenosis. The benefit of carotid endarterectomy in patients of 75 years and older remains unclear. METHODS: Patients aged 75 years or older from the North American Symptomatic Carotid Endarterectomy Trial were compared with those aged 65-74 years and less than 65 years for baseline characteristics and risk of ipsilateral ischaemic stroke at 2 years by degree of stenosis and treatment group. FINDINGS: Among patients with 70-99% stenosis, the absolute risk reduction of ipsilateral ischaemic stroke with carotid endarterectomy was 28.9% (95% CI 12.9-44.9) for patients aged 75 years or older (n=71), 15.1% (7.2-23.0) for those aged 65-74 years (n=285), and 9.7% (1.5-17.9) for the youngest group (n=303). Among patients with 50-69% stenosis, the absolute risk reduction was significant only in those of 75 years and older (n=145; 17.3% [6.6-28.0]). The perioperative risk of stroke and death at any degree of stenosis was 5.2% for the oldest group, 5.5% for 65-74 years, and 7.9% for less than 65 years. The number of patients aged 75 years or older needed to treat to prevent one ipsilateral stroke within 2 years was three with 70-99% stenosis and six with 50-69% stenosis. INTERPRETATION: In the prevention of ipsilateral ischaemic stroke, elderly patients with 50-99% symptomatic carotid stenosis benefited more from carotid endarterectomy than younger patients did. To achieve this treatment benefit, surgeons must be skilled and patients with other life-threatening illnesses must be excluded.

The causes and risk of stroke in patients with asymptomatic internal-carotid-artery stenosis. North American Symptomatic Carotid Endarterectomy Trial Collaborators.

BACKGROUND: The causes of stroke in patients with asymptomatic carotid-artery stenosis have not been carefully studied. Information about causes might influence decisions about the use of carotid endarterectomy in such patients. METHODS: We studied patients with unilateral symptomatic carotid-artery stenosis and asymptomatic contralateral stenosis from 1988 to 1997. The causes, severity, risk, and predictors of stroke in the territory of the asymptomatic artery were examined and quantified. RESULTS: The risk of stroke at five years after study entry in a total of 1820 patients increased with the severity of stenosis. Among 1604 patients with stenosis of less than 60 percent of the luminal diameter, the risk of a first stroke was 8.0 percent (1.6 percent annually), as compared with 16.2 percent (3.2 percent annually) among 216 patients with 60 to 99 percent stenosis. In the group with 60 to 99 percent stenosis, the five-year risk of stroke in the territory of a large artery was 9.9 percent, that of lacunar stroke was 6.0 percent, and that of cardioembolic stroke 2.1 percent. Some patients had more than one stroke of more than one cause. In the territory of an asymptomatic occluded artery (as was identified in 86 patients), the annualized risk of stroke was 1.9 percent. Strokes with different causes had different risk factors. The risk factors for large-artery stroke were silent brain infarction, a history of diabetes, and a higher degree of stenosis; for cardioembolic stroke, a history of myocardial infarction or angina and hypertension; for lacunar stroke, age of 75 years or older, hypertension, diabetes, and a higher degree of stenosis. CONCLUSIONS: The risk of stroke among patients with asymptomatic carotid-artery stenosis is relatively low. Forty-five percent of strokes in patients with asymptomatic stenosis of 60 to 99 percent are attributable to lacunes or cardioembolism. These observations have implications for the use of endarterectomy in asymptomatic patients. Without analysis of the risk of stroke according to cause, the absolute benefit associated with endarterectomy may be overestimated.