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.

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.

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.

Benefit of carotid endarterectomy in patients with symptomatic moderate or severe stenosis. North American Symptomatic Carotid Endarterectomy Trial Collaborators.

BACKGROUND: Previous studies have shown that carotid endarterectomy in patients with symptomatic severe carotid stenosis (defined as stenosis of 70 to 99 percent of the luminal diameter) is beneficial up to two years after the procedure. In this clinical trial, we assessed the benefit of carotid endarterectomy in patients with symptomatic moderate stenosis, defined as stenosis of less than 70 percent. We also studied the durability of the benefit of endarterectomy in patients with severe stenosis over eight years of follow-up. METHODS: Patients who had moderate carotid stenosis and transient ischemic attacks or nondisabling strokes on the same side as the stenosis (ipsilateral) within 180 days before study entry were stratified according to the degree of stenosis (50 to 69 percent or <50 percent) and randomly assigned either to undergo carotid endarterectomy (1108 patients) or to receive medical care alone (1118 patients). The average follow-up was five years, and complete data on outcome events were available for 99.7 percent of the patients. The primary outcome event was any fatal or nonfatal stroke ipsilateral to the stenosis for which the patient underwent randomization. RESULTS: Among patients with stenosis of 50 to 69 percent, the five-year rate of any ipsilateral stroke (failure rate) was 15.7 percent among patients treated surgically and 22.2 percent among those treated medically (P=0.045); to prevent one ipsilateral stroke during the five-year period, 15 patients would have to be treated with carotid endarterectomy. Among patients with less than 50 percent stenosis, the failure rate was not significantly lower in the group treated with endarterectomy (14.9 percent) than in the medically treated group (18.7 percent, P=0.16). Among the patients with severe stenosis who underwent endarterectomy, the 30-day rate of death or disabling ipsilateral stroke persisting at 90 days was 2.1 percent; this rate increased to only 6.7 percent at 8 years. Benefit was greatest among men, patients with recent stroke as the qualifying event, and patients with hemispheric symptoms. CONCLUSIONS: Endarterectomy in patients with symptomatic moderate carotid stenosis of 50 to 69 percent yielded only a moderate reduction in the risk of stroke. Decisions about treatment for patients in this category must take into account recognized risk factors, and exceptional surgical skill is obligatory if carotid endarterectomy is to be performed. Patients with stenosis of less than 50 percent did not benefit from surgery. Patients with severe stenosis (> or =70 percent) had a durable benefit from endarterectomy at eight years of follow-up.

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.

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.

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.

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.

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.