Antiplatelet, Lipid-Lowering Therapy Associated With Absence of Embolic Signals on TCD

May 22, 2008 (Nice, France) — An analysis of baseline data from an ongoing study assessing the value of transcranial Doppler (TCD) in predicting stroke risk among patients with asymptomatic carotid stenosis shows a negative association between the presence of embolic signals and antiplatelet and statin therapy.

"The baseline results show associations between drug therapy and asymptomatic embolization, with antiplatelet therapy associated with fewer embolic signals and statin therapy associated with fewer embolic signals as well, possibly reflecting plaque stabilization," Raffi Topakian, MD, from the Academic Teaching Hospital Wagner-Jauregg, in Linz, Austria, told delegates here at the 17th European Stroke Conference.

The analysis, from the ongoing Asymptomatic Carotid Emboli Study (ACES), was presented here at the 17th European Stroke Conference.

Predicting the Risk for Asymptomatic Stenoses

The risk for stroke in asymptomatic carotid stenosis is relatively low, about 2% per annum, Dr. Topakian said. "Operating on all patients with tight stenosis has small benefits," he said. "For every 85 people operated on in clinical studies, about 1 stroke is prevented per year. For ever 32 operations, 1 disabling stroke is prevented over 5 years."

Better selection of high-risk patients with asymptomatic carotid stenosis might improve risk/benefit ratios and identify those who would preferentially benefit from carotid endarterectomy. One potential tool to identify high-risk patients is the detection of carotid embolic signals using TCD. Detection of embolic signals has been shown to predict stroke risk in symptomatic carotid stenosis, but studies of its use in asymptomatic patients have produced conflicting results, Dr. Topakian said.

ACES is a large, multicenter, international study, funded by the British Heart Foundation, that aims to answer this question of whether the presence of embolic signals can predict the risk for stroke or transient ischemic attack in patients with asymptomatic carotid stenosis.

Patients enrolled in the trial had to have carotid stenosis of 70% to 99% and must have been asymptomatic for at least 2 years. They also had to be asymptomatic in the contralateral carotid or vertebrobasilar territory, again for at least 2 years, or if contralateral surgery or stenting had been performed, patients were eligible after 1 year as long as they had been asymptomatic in the interim. Patients were eligible whether they were taking antiplatelet or anticoagulant therapy, he noted.

The primary aim of ACES is to determine whether the presence of embolic signals on either of two 1-hour recordings at study entry predicts ipsilateral transient ischemic attack or stroke risk during the following 2 years, Dr. Topakian said. The secondary end point is whether embolic signals on a single 1-hour recording predict ipsilateral transient ischemic attack or stroke risk during the subsequent 6-month period.

Power calculations for the ACES study were done based on interim blinded data from the first 132 subjects enrolled because previous data on this topic were "very sparse," he said. Of the enrolled patients, 12.1% had embolic signals on the first of 2 entry recordings, and 21.2% had embolic signals on either of the 2 entry recordings. The 3-year combined ipsilateral stroke and transient ischemic attack rate was 6.6%. On this basis, and assuming that the risk for stroke or transient ischemic attack in embolic-signal–positive (ES+) patients would be 3 times higher than in embolic-signal–negative (ES-) patients, they calculated a sample size of 480 for the primary end point, and 340 patients for the secondary end point.

After the 2 baseline TCD recordings at entry, done 1 week apart, patients are being followed up every 6 months, up to 24 months. Recruitment was completed in October of 2007, with 482 patients enrolled from 26 centers in 17 countries in Europe, Asia, and the United States. All TCD recordings are reviewed at a coordinating center by a human observer blinded to clinical information. Embolic signals are defined using an intensity threshold of more than 70 dBs. TCD recordings are considered ES+ if any embolic signal was detected on either of the 2 baseline recordings and ES- if no such signals were detected.

At the meeting here, Dr. Topakian presented the baseline data, showing that the mean age of patients is about 71.5 years, 25% are women, 90% have hypertension, and 20% have diabetes. Some 15% are current smokers, and 20% have contralateral carotid occlusive disease of 70% or greater. The majority of patients, 88%, were taking antiplatelet agents at baseline, and 66% were taking lipid-lowering therapy, almost exclusively statins, he noted.

All baseline recordings have now been analyzed, a total of 1748 hours, and from these, 366 embolic signals have been detected. A total of 149 of these hours, or 8.5%, were ES+, he said.

When they compared baseline characteristics among those who were ES- and ES+, they found 2 factors, antiplatelet therapy and lipid-lowering agents, were significantly associated with the absence of embolic signals on TCD.

Final follow-up of the ACES trial is expected to be completed in October of 2009, he concluded.

The ACES study is funded by the British Heart Foundation.

17th European Stroke Conference: Large Clinical Trials II. Presented Friday, May 16, 2008.

Medscape Medical News © 2008  Medscape

Cite this: Susan Jeffrey. Antiplatelet, Lipid-Lowering Therapy Associated With Absence of Embolic Signals on TCD - Medscape - May 22, 2008.