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Asymptomatic cerebral lesions after carotid artery stenting (CAS), although common, do not affect longer-term hard outcomes, according to a study published online March 20, 2013, ahead of print in JACC: Cardiovascular Interventions. Whether these ischemic signals have an adverse impact on cognitive function remains unknown.

Joachim Schofer, MD, PhD, and colleagues of Hamburg University Cardiovascular Center (Hamburg, Germany), followed 728 patients who underwent CAS with embolic protection between February 2001 and December 2010. All were imaged with diffusion-weighted magnetic resonance imaging (DW-MRI) before and 12 to 24 hours after the procedure.

Before CAS, no patients had acute cerebral ischemic lesions. After the procedure, new lesions were detected in 241 patients (32.8%). At 30-day follow-up, 15 patients (1.79%) experienced MACCE (composite of stroke, MI, and death), including 1 death and 14 strokes (9 minor and 5 major), and were then excluded from further analysis.

No Clear Long-term Effects

At a mean follow-up of 766.8 days, the MACCE rate was 6.2%. Thirty-four patients died (10 from cardiovascular causes, 5 from stroke, and 19 of unknown causes), 10 sustained a nonfatal stroke (5 minor and 5 major), and 3 had an MI. The overall 2-year MACCE-free survival rate was 92.9%.

Multivariate analysis found diabetes to be the only independent risk factor for MACCE during follow-up (HR 3.3; 95% CI 1.7-6.6; P = 0.001). All other clinical, procedural, and lesion characteristics as well as positive DW-MRI had no impact on long-term prognosis. Supporting this analysis, Kaplan-Meier estimates showed that diabetic patients had lower MACCE-free survival than diabetic patients (86.6% vs. 95.7%; log rank P < 0.0001).

Interestingly, the current study identifies diabetes as the only risk factor, the authors note, whereas an earlier study pointed to the combination of low HDL cholesterol and elevated inflammatory markers as a predictor of long-term MACCE (Cremonesi A, et al. EuroIntervention. 2009;5:589-598). The finding suggests that diabetic patients need intensive treatment and careful surveillance, they say.

Strategies to Minimize Lesions

In an e-mail communication with TCTMD, Dr. Schofer cautioned that these silent lesions “should not be considered benign before we have looked for longer-term cognitive effects.”

Meanwhile, interventionalists should continue to deploy the most effective embolic protection during CAS to try to prevent ischemic events, Dr. Schofer said. He noted that in the randomized PROFI study, proximal balloon occlusion as compared with filter protection (the type of protection used in the vast majority of patients in the current study) significantly reduced the embolic load to the brain (Bijuklic K, et al. J Am Coll Cardiol. 2012;59:1382-1389).

Improved technique may also help minimize silent ischemic events, Dr. Schofer suggested. About a quarter of DW-MRI lesions occur in the contralateral hemisphere, and these seem to be related to catheter crossing of the aortic arch and probing of the target vessel, he reported. In addition, stent expansion is associated with ischemic signals on transcranial Doppler imaging, and improved stent coverage may be a way to reduce their incidence.

Refining the antiplatelet regimen for CAS may be another helpful measure, Dr. Schofer added, since cerebral events occur in about 20% of patients up to 24 hours after the procedure.

Cognitive Impact Unresolved

In a telephone interview with TCTMD, Daryl R. Gress, MD, of the University of Virginia, Charlottesville (Charlottesville, VA), said it is “reassuring that these asymptomatic lesions are not a marker for later major vascular events, although I wouldn’t have predicted that they would be.”

However, he continued, “the major concern is the potential role [of these lesions] in long-term cognitive decline, and there remains insufficient evidence to come to any conclusions about that.” Unfortunately, research to answer the question is “extraordinarily difficult” to conduct, he added, because cognitive function is not as quantifiable as defects like aphasia and many other vascular risk factors contribute to cognitive decline.

“In this period where we don’t understand the potential risks of these [silent] lesions, we should do everything we can to minimize their number,” Dr. Gress said, adding, “I think distal protection devices have some benefit, but their demonstrated efficacy leaves room for improvement.” He was less convinced of the potential of improved antiplatelet regimens, explaining that lesions may be caused by cholesterol crystals or plaque fragments as well as by platelet aggregation.

Meanwhile, vigilance in regard to these ischemic signals is definitely warranted, Dr. Gress advised, especially since they are seen after a range of vascular procedures, from ablation for A-fib to CABG and TAVR and even to conventional coronary angiography. “I think it’s our responsibility to minimize [these lesions] until we are convinced that they are safe,” he concluded.

Study Details

Patients were administered dual antiplatelet therapy (aspirin 100 mg and clopidogrel 75 mg daily) before the intervention and for 4 weeks thereafter. Embolic protection consisted of filters in 94.2% of patients and occlusive protection in 5.8%.

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