Revascularization strategies for extracranial carotid artery disease: Winners and losers

Issue: December 2009

ByMichael R. Jaff, DO

The morbidity and mortality relating to stroke remain unacceptably high. Estimates suggest that it accounts for approximately one of every 17 deaths in the United States, and that someone dies from the direct consequences of stroke every three to four minutes.

The accessibility of the extracranial carotid circulation to revascularization, together with the strong correlation between the severity of extracranial carotid artery stenosis and the risk for stroke in patients who have already experienced a transient ischemic attack or stroke (up to 35% at five years in one series), has driven the advances in carotid artery endarterectomy (CAE) and carotid artery stenting (CAS).

NASCET and ECST were the pivotal trials in the 1980s and ’90s, demonstrating efficacy of CEA for extracranial carotid disease. In NASCET, 595 symptomatic patients (those with a recent hemispheric transient ischemic attack or mild stroke and ipsilateral carotid artery stenosis of 70% to 99%) were randomly assigned to best medical care (n=295) or best medical care and CEA. In the CEA group, the 30-day combined stroke and mortality rate was 5%, and the absolute risk reduction at 18 months was 7% compared with the medically treated group.

The ECST was a multicenter, randomized trial involving more than 3,000 patients with at least one transient ischemic attack or mild ischemic cerebrovascular accident within six months before enrollment. Despite the immediate risks of CEA, patients with severe stenosis (>80%) had the greatest benefit, with a reduction in major stroke or death by more than 11% at three years.

Michael R. Jaff, DO

The Veterans Affairs Cooperative StudiesProgram compared CEA with best medical management (n=91) vs. best medical management alone (n=98) in symptomatic men with more than 50% ipsilateral carotid artery stenosis. Overall, similar results were obtained in tandem with the two larger aforementioned trials.

Endovascular therapy for extracranial carotid artery stenosis began with percutaneous balloon angioplasty in the late 1970s and early 1980s in patients deemed unsuitable for CEA. Researchers of the CAVATAS study randomly assigned 251 patients to endovascular therapy and 253 to CEA; 97% of patients were described as symptomatic with a mean carotid artery stenosis of 75.2%. Only 26% of patients received stent implantation with the majority being treated with balloon angioplasty. No significant difference was observed in the rates of disabling stroke or death (6.4% vs. 5.9%) between the two treatment modalities. Although endovascular treatment led to higher 12-month restenosis rates (14% vs. 4%), there was no difference in the rate of ipsilateral stroke during three-year follow-up.

The Wallstent trial involved 219 symptomatic patients with 60% to 99% stenosis who underwent CAS without embolic protection or CEA. Thirty-day cerebrovascular accident rates were 12.1% in the CAS group vs. 4.5% treated with CEA. At one year, 12.1% of stented patients had an ipsilateral stroke or procedure/vascular-related death compared with 3.6% of the surgical patients (P=.022).

CaRESS was one of the early studies to involve CAS with embolic protection. Death or stroke rates at 30 days (2.1% vs. 3.6%) and one year (10% vs. 13.6%) were nonsignificantly different between the two treatments.

The SAPPHIRE trial was the first major comparative trial comparing CEA with CAS in patients at high risk for complications relating to carotid surgery. Of the 167 high-risk patients randomly assigned to CAS, 29.9% were symptomatic; as were 27.7% of those who underwent CEA.

Embolic protection was used in more than 95% of CAS procedures. The primary endpoint, which was cumulative incidence of major CV events at one year (defined as death, stroke or MI within 30 days of the procedure), occurred in 12.2% of patients with CAS and in 20.1% of those with CEA. The investigators concluded that CAS with embolic protection was not inferior to CEA in high-risk patients with regard to prevention of stroke, death or MI.

The EVA-3S trial yielded poorer outcomes in those managed with CAS. This French-based multicenter trial involved 520 patients with symptomatic carotid artery disease who were randomly assigned to CEA or CAS. The incidence of any stroke or death was 3.9% (95% CI, 2.0-7.2) after CEA and 9.6% (95% CI, 6.4-14.0) in the CAS group. The CAS group had a six-month stroke or death rate that greatly exceeded that of those treated with CEA (11.7 vs. 6.1%; P=.02). Serious misgivings have been expressed about the limited experience of the operators performing CAS in this trial.

CREST includes standard risk symptomatic patients with more than 50% stenosis and those without symptoms with co-existing severe carotid artery stenosis (>70%). Initial reports have yielded a 5.7% rate of stroke or death after 30 days for symptomatic patients undergoing CAS. The corresponding value for patients older than 80 years was 12.1%.

ICSS/CAVATAS 2 researchers are enrolling symptomatic patients who are suitable for CAS or surgery, with a target recruitment of 1,500 by completion. As of yet, the cumulative incidence of stroke, MI or death was 8.5% in CAS patients vs. 5.1% in those with CEA. Sixty-five patients who underwent CAS experienced stroke compared with 34 who had CEA. Long-term results are expected in 2011.

Currently, CEA remains the primary stroke prevention strategy for patients with extracranial carotid stenosis. However, emerging data suggest that CAS offers a safe and reasonable alternative. The results of CREST will provide significant data that will help us more effectively treat our patients.

Michael R. Jaff, DO, is from the Division of Vascular Medicine at Massachusetts General Hospital, Harvard Medical School, Boston and a member of the Cardiology Today Editorial board.

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