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New Trial Proposed for Asymptomatic Carotid Stenosis

By: BETSY BATES, Frontline Medical News

12/19/11

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Perspectives Study With Care

SAN DIEGO – Citing vastly improved management of carotid stenosis, the principal investigator of the Carotid Revascularization Endarterectomy vs. Stenting Trial has called for yet another trial, this one to clarify risks and benefits of carotid revascularization with either endarterectomy or stenting vs. aggressive medical management to prevent stroke in asymptomatic patients.

Every contemporary intervention to prevent strokes – endarterectomy, carotid stenting, and aggressive medical management of risk factors – is becoming safer and more efficacious, said Dr. Thomas G. Brott of the Mayo Clinic, Jacksonville, Fla., at the opening symposium of the annual meeting of the American Neurological Association.

The dilemma, according to Dr. Brott: "We don’t know how they stack up."

"Unfortunately, the new opinions outweigh the new data."

Current clinical practice was shaped by results of the ACAS (Asymptomatic Carotid Atherosclerosis Study) and the ACST (Asymptomatic Carotid Surgery Trial), in which carotid endarterectomy (CEA) trumped medical management for prevention of stroke, Dr. Brott explained.

CREST (Carotid Revascularization Endarterectomy vs. Stenting Trial), which began enrolling only symptomatic patients, added asymptomatic subjects after publication of ACST results in 2004. In the end, it concluded that perioperative stroke and death rates were "low and similar" for stenting (2.5%) and endarterectomy (1.4%).

Revascularization with carotid artery stenting has remained somewhat controversial, with the current body of evidence suggesting the need for better control of rare, but real, complications and mortality, particularly in certain populations, including Medicare patients.

Meanwhile, recent epidemiologic studies demonstrate profoundly lowered stroke rates without surgery or stenting, via intensive medical therapy to control risk factors such as hypertension, hyperlipidemia, and insulin resistance. For example, a population-based study in the United Kingdom found that the rate of ipsilateral stroke in medically treated patients who had carotid stenosis of 50% or greater was 0.3%.

Two new, randomized trials suggest that intensive medical therapy can indeed produce far more impressive results than anticipated in a prospective study of patients with asymptomatic carotid stenosis (Arch. Neurol. 2010;67:180-6), and even in patients with severe intracranial artery stenosis in the SAMMPRIS (Stenting vs. Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis) trial (N. Engl. J. Med. 2011;365:993-1003), Dr. Brott noted.

Various groups, including the Centers for Medicare and Medicaid Services, the American Heart Association, and the American Stroke Association, have weighed in with opinions on the management of asymptomatic patients in the hopes of preventing an estimated 5%-10% of all strokes.

The problem, Dr. Brott said, is not a lack of guidance for current treatment decisions, but the lack of a direct comparison of carotid revascularization (either endarterectomy or stenting) vs. contemporary medical therapy.

"We have evolving opinion without evolving data," he asserted.

Much is at stake, with carotid endarterectomy selected for 80,000-90,000 asymptomatic patients each year in the United States, and carotid artery stenting for another 40,000 patients.

Dr. Brott proposed a trial to enroll 950 patients at 70 centers, with the CREST team providing the interventional arm (either endarterectomy or stenting) and the SAMMPRIS team providing the medical management arm in asymptomatic patients exhibiting at least 70% carotid stenosis by angiography or ultrasound.

The effect size proposed by Dr. Brott of 1.2% would be equal to the absolute difference in the primary end point (periprocedural stroke and death or subsequent ipsilateral stroke) in the ACAS trial, a difference substantial enough to alter clinical practice.

"We think such a trial can be done in a reasonable amount of time and provide us with ... contemporary data," he said.

Dr. Walter J. Koroshetz, deputy director of the National Institute of Neurological Disorders and Stroke, said by e-mail that a grant proposal for such a study has been received by the institute, but he would not elaborate on its feasibility or methodology, noting that the institute’s "leadership depends heavily on ... peer review study sections to provide advice."

Dr. Brott said that he had no relevant financial disclosures.

Perspectives
Study With Care

There is building consensus among vascular surgeons and other providers who manage patients with asymptomatic carotid stenosis that the results from the medical arm of ACAS are obsolete considering current medical therapy.  For instance, since ACAS was published, statin use has become very prevalent.  I agree that a modern trial comparing carotid intervention with medical therapy is necessary but the design of such a trial should be carefully considered.  

It would be a huge mistake to fail to stratify for high-grade (~80%) v moderate (~50-79%) stenosis with enough power in each group to draw separate conclusions.  Similarly, it would be a mistake not to include morphological studies of plaque composition (calcification, hemorrhage, fibrous cap thickness, necrotic core size) which are now possible with sophisticated MRI protocols.  Whether these important study design elements can be satisfied with a trial of 950 patients is unclear from this report of Dr Brott’s comments.  In particular, a trial that fails to discriminate between high- and moderate-risk patients by lumping them all together will have little credibility upon completion and is likely to be money wasted.  

Larry W Kraiss M.D., is professor & Chief, Vascular Surgery, University of Utah, Salt Lake City. 

An increasing body of evidence suggests that the risk of stroke (on medical therapy alone) in patients with asymptomatic carotid stenoses is lower than when ACAS and ACST were recruiting. In addition to the epidemiological study quoted by Dr Brott, a number of studies (including data from ACAS and ACST) have suggested that the annualized risk of stroke in medically treated patients has diminished considerably over the last 15 years. We should therefore actively support this study, which will hopefully enable the identification of a smaller cohort of ‘high risk for stroke’ patients in whom to target surgery or stenting in the future”.

A Ross Naylor M.D., is a professor of vascular surgery at Leicester Royal Infirmary, Leicester UK. He has written an extended editorial upon this issue.
 

Vascular Therapies Resource - Results from 36-month study support single stent strategy. LEARN MORE.

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