Three important questions on how to treat asymptomatic carotid stenosis patients were addressed by Thomas G Brott, neurologist, director for Research, Mayo Clinic, Jacksonville, USA. In the presentation titled ‘Where do we go from here with randomised trials of carotid artery stenting vs. carotid endarterectomy?’ Brott was challenged to answer if the field needs more trials with asymptomatic patients, better patient selection, and more trials with improved stents.
Brott started the presentation telling delegates that we need more trials in asymptomatic patients with a best medical treatment arm.
“We need information about asymptomatic patients. In part because of how many carotid interventions are done each year. There has been a drop in recent years, but we still have over 120,000 carotid interventions done each year in the United States and most of these procedures are done for asymptomatic patients,” he said.
More information is also needed, Brott said, because many physicians still wonder what to do about many patients. He exemplified with the case of a non-smoker with 70–80% stenosis, irregular plaque and 20% stenosis of the left internal carotid artery.
“What is your advice?” he questioned. He reminded delegates of the worldwide survey Management of Carotid Stenosis (N Engl J Med 2008;358:1617–1621) which showed that best medical treatment is favoured over any intervention in all continents. “Many of our colleagues prefer medical therapy over either stenting or surgery,” he said.
Brott said that, on the medical therapy side, the 2% annual medical risk of stroke that drove the difference between the surgical and medical arms in the ACAS (Asymptomatic carotid atherosclerosis study) and ACST (Asymptomatic carotid surgery trial) is probably too high today and could have something to do with the drop in carotid interventions seen in recent years.
He mentioned a range of improvements in medical therapy with statins, which decrease rates of stroke, myocardial infarction, decrease stroke severity, and impact on surrogate endpoints. In these improvements, Brott also included new hypertensive drugs – more effective and better tolerated (with the potential for greater compliance) – new antiplatelet drugs, potential for pharmacogenomic-guided choices, better treatments and glucose monitoring for diabetes, and ongoing drop in cigarette smoking. “In Europe cigarette smoking has dropped by 30%, and it is still dropping,” he said. “The medical side has made great advances. It is time to do the comparison between carotid intervention and best medical treatment in asymptomatic patients again.”
Do we need more trials with better patient selection? Although Brott told delegates that “yes, we do”, he added a “but”. “SPACE and CREST trials lead-in data showed relatively greater risk following stenting for those aged over 75 years. Probably about 25% of our patients in CREST are older than 75 years. How do we select them? We think studies have shown that severe tortuosity and heavy calcification are predictors of risk. Probably teasing out the variables in older patients, we will see that the endpoints are confounded by stroke from other causes, probably small vessels stroke, and decline in follow-up. Older patients develop or have already developed increasing morbidities. And we found in CREST that it is a real challenge to follow-up older patients, as their spouse becomes disabled or dies, transportation becomes more of a problem, and the effects of other diseases have their impact,” Brott said.
Do we need more trials with better technology for stenting (flow reversal and better stent systems)? “No, at least not randomised controlled trials,” Brott told delegates. “Randomised controlled trials are not the answer for everything, the arithmetic is prohibitive. In all trials the sample size increases as the effect size decreases. We already have good results from good technology. Proving the effects of ‘better’ technology would require more than 2,500 patients.”
Current status of the CREST trial
Wesley Moore, professor and chief emeritus, Division of Vascular Surgery, University of California Los Angeles Medical Center, reviewed the results from CREST, which is the largest trial to date that has randomised patients prospectively to either protected stent/angioplasty or carotid endarterectomy. This trial has several unique features, which Moore believes make it a superior study to those done in the past. One of the most important features is that the interventionalist has to be approved by a committee before they can perform carotid stenting.
This is to ensure that patients are treated by physicians with the appropriate background and experience. Thus, contrary to other trials, interventionalists were carefully selected and must be considered the top performers of carotid artery stenting.
This enables CREST to critically compare the outcome of the most talented interventionalists with the results of contemporary carotid endarterectomy.
Since the last patient was randomised in June 2008, Moore had intended to report one-year data, but due to administrative delays, the results are still in analysis, with expected publication in February or March, 2010. At the VEITHsymposium, Moore did report that the endpoint (death, stroke, or myocardial infarction) rate does statistically increase with age and bleeding complications.