Ten-year risk of stroke in patients with previous cerebral infarction and the impact of carotid surgery in the Asymptomatic Carotid Surgery Trial

Background: Silent brain infarcts are common in patients at increased risk of stroke and are associated with a poor prognosis. In patients with asymptomatic carotid stenosis, similar adverse associations were claimed, but the impact of previous infarction or symptoms on the beneficial effects of carotid endarterectomy is not clear. Our aim was to evaluate the impact of prior cerebral infarction in patients enrolled in the Asymptomatic Carotid Surgery Trial, a large trial with 10-year follow-up in which participants whose carotid stenosis had not caused symptoms for at least six months were randomly allocated either immediate or deferred carotid endarterectomy.

Methods: The first Asymptomatic Carotid Surgery Trial included 3120 patients. Of these, 2333 patients with baseline brain imaging were identified and divided into two groups irrespective of treatment assignment, 1331 with evidence of previous cerebral infarction, defined as a history of ischemic stroke or transient ischemic attack > 6 months prior to randomization or radiological evidence of an asymptomatic infarct (group 1) and 1002 with normal imaging and no prior stroke or transient ischemic attack (group 2). Stroke and vascular deaths were compared during follow-up, and the impact of carotid endarterectomy was observed in both groups.

Results: Baseline characteristics of patients with and without baseline brain imaging were broadly similar. Of those included in the present report, male gender and hypertension were more common in group 1, while mean ipsilateral stenosis was slightly greater in group 2. At 10 years follow-up, stroke was more common among participants with cerebral infarction before randomization (absolute risk increase 5.8% (1.8-9.8), p = 0.004), and the risk of stroke and vascular death was also higher in this group (absolute risk increase 6.9% (1.9-12.0), p = 0.007). On multivariate analysis, prior cerebral infarction was associated with a greater risk of stroke (hazard ratio = 1.51, 95% confidence interval: 1.17-1.95, p = 0.002) and of stroke or other vascular death (hazard ratio = 1.30, 95% confidence interval: 1.11-1.52, p = 0.001). At 10 years, greater absolute benefits from immediate carotid endarterectomy were seen in those patients with prior cerebral infarction (6.7% strokes immediate carotid endarterectomy vs. 14.7% delayed carotid endarterectomy; hazard ratio 0.47 (0.34-0.65), p = 0.003), compared to those lower risk patients without prior cerebral infarction (6.0% vs. 9.9%, respectively; hazard ratio 0.61 (0.39-0.94), p = 0.005), though it must be emphasized that the first Asymptomatic Carotid Surgery Trial was not designed to test this retrospective and non-randomized comparison.

Conclusions: Asymptomatic carotid stenosis patients with prior cerebral infarction have a higher stroke risk during long-term follow-up than those without prior cerebral infarction. Evidence of prior ischemic events might help identify patients in whom carotid intervention is particularly beneficial.