Asymptomatic embolisation for prediction of stroke in the Asymptomatic Carotid Emboli Study (ACES): a prospective observational study

Abstract

Background: Whether surgery is beneficial for patients with asymptomatic carotid stenosis is controversial. Better methods of identifying patients who are likely to develop stroke would improve the risk-benefit ratio for carotid endarterectomy. We aimed to investigate whether detection of asymptomatic embolic signals by use of transcranial doppler (TCD) could predict stroke risk in patients with asymptomatic carotid stenosis.

Methods: The Asymptomatic Carotid Emboli Study (ACES) was a prospective observational study in patients with asymptomatic carotid stenosis of at least 70% from 26 centres worldwide. To detect the presence of embolic signals, patients had two 1 h TCD recordings from the ipsilateral middle cerebral artery at baseline and one 1 h recording at 6, 12, and 18 months. Patients were followed up for 2 years. The primary endpoint was ipsilateral stroke and transient ischaemic attack. All recordings were analysed centrally by investigators masked to patient identity.

Findings: 482 patients were recruited, of whom 467 had evaluable recordings. Embolic signals were present in 77 of 467 patients at baseline. The hazard ratio for the risk of ipsilateral stroke and transient ischaemic attack from baseline to 2 years in patients with embolic signals compared with those without was 2.54 (95% CI 1.20-5.36; p=0.015). For ipsilateral stroke alone, the hazard ratio was 5.57 (1.61-19.32; p=0.007). The absolute annual risk of ipsilateral stroke or transient ischaemic attack between baseline and 2 years was 7.13% in patients with embolic signals and 3.04% in those without, and for ipsilateral stroke was 3.62% in patients with embolic signals and 0.70% in those without. The hazard ratio for the risk of ipsilateral stroke and transient ischaemic attack for patients who had embolic signals on the recording preceding the next 6-month follow-up compared with those who did not was 2.63 (95% CI 1.01-6.88; p=0.049), and for ipsilateral stroke alone the hazard ratio was 6.37 (1.59-25.57; p=0.009). Controlling for antiplatelet therapy, degree of stenosis, and other risk factors did not alter the results.

Interpretation: Detection of asymptomatic embolisation on TCD can be used to identify patients with asymptomatic carotid stenosis who are at a higher risk of stroke and transient ischaemic attack, and also those with a low absolute stroke risk. Assessment of the presence of embolic signals on TCD might be useful in the selection of patients with asymptomatic carotid stenosis who are likely to benefit from endarterectomy.

Funding: British Heart Foundation.

Figure 1

Survival plots for the association between the presence of embolic signals and cumulative event rates for the analysis of whether embolic signals at baseline predict risk 77 patients had embolic signals and 390 did not. TIA=transient ischaemic attack.

Figure 2

Survival plots for the association between the presence of embolic signals and cumulative event rates for the analysis of whether embolic signals at the start of each 6-month interval predict risk over the subsequent 6-month period 111 recordings had embolic signals and 1333 did not. TIA=transient ischaemic attack.

Figure 3

Meta-analyses of ACES with previous studies of the association of embolic signals with future risk of ipsilateral stroke or ipsilateral stroke and TIA TIA=transient ischaemic attack.