Asymptomatic Carotid Stenosis and Risk of Stroke: A Natural History Study

Abstract

In patients with asymptomatic carotid stenosis >70% diameter, the annual incidence of ipsilateral stroke is 3-4%. Multicentre randomised studies such as the asymptomatic carotid atherosclerosis study (ACAS) in the U.S.A. and the ACST in Europe aim to answer the question whether carotid endarterectomy can reduce the incidence of stroke in such patients. If the surgical risk is too close to benefit or if a high proportion of patients not at risk of stroke are entered into the ACAS or ACST studies, the latter may fail to demonstrate the benefit of carotid endarterectomy (CE). The need to identify a high risk stroke group (ipsilateral stroke >7% per annum) with randomisation of this group to a subsequent study will then become apparent. If the ACAS and ACST studies indicate that the risk of stroke is reduced by 50% (i.e., from 4 to 2%), it has been calculated that the cost of preventing one stroke will be 1.2 million US dollars because of the large number of operations required. It will still be necessary to identify a high-risk group or, better, a low-risk group in order to spare many patients unnecessary operation. A multicentre, natural history study has been set up under the auspices of the International Union of Angiology and monitored from St Mary's Hospital Medical School in London with over 50 centres taking part. Patients with asymptomatic carotid stenosis 50-70% and 70-90% are entered in a ratio of 1 to 2, a number of noninvasive tests are performed, and the patients are followed for 5 years. The tests performed are (a) Grading the degree of internal carotid stenosis using duplex scanning; (b) grading the opposite side; (c) plaque characterisation; (d) presence of ultrasonic ulceration; (e) plaque thickness (mm); (f) cerebral reactivity to CO₂ using velocity of internal carotid artery and (optional) middle cerebral artery ; (g) CT brain scan for the presence of silent infarction ; (h) intima-media thickness of the common carotid; and (i) identification of conventional risk factors: hypertension, hypercholeterolaemia, smoking, family history, diabetes. The key end points are stroke (including fatal stroke) and ipsilateral stroke. Patients who die from cardiovascular death other than stroke or noncardiovascular death and patients who develop hemispheric transient ischaemic attacks followed by CE are considered to have reached an exit end point. Because this is a natural history study, the clinician in charge of all patients is free to treat them in any way considered appropriate. Patients in the Medical Limb of the ACST study may be entered into the Natural History (ACSRS) study.