CREST: Further Data Analysis Confirms Wisdom of Appropriate Patient Stratification

What can you tell us about the latest findings from the CREST trial (Carotid Revascularization Endarterectomy vs. Stenting Trial) and the further evaluation of the data?

There is now more “texture” to the data, but the conclusion is still that there are no significant differences between the outcomes with carotid artery stenting (CAS) and carotid endarterectomy (CEA). In essence, there were more minor strokes in the CAS group and more myocardial infarctions (MI) in the CEA group. Since there were three endpoints, they essentially evened out. The debates have tended to focus on the surgeons who perform CEA saying that strokes are worse than heart attacks and interventional cardiologists saying that MIs are worse than strokes. But this is nonsense — nobody wants a patient to have a stroke — big or small — and nobody wants a patient to have an MI. I do think that the differences are real and the CREST data are strong, and that this is an excellent study. These data allow us to better stratify patients for one procedure or the other based on their risk factors, such that those at risk for an MI should probably not undergo surgery, while those more at risk for stroke should probably undergo surgery as opposed to stenting.There are certain anatomic features of carotid lesions that allow for more appropriate patient stratification. For example, heavily calcified or very tortuous carotid lesions render carotid stenting difficult. Those patients should clearly be sent for CEA instead of CAS. Patients with coronary artery disease — even those who are not very symptomatic — would likely fare better with a non-surgical approach to treat their carotid stenosis. So these risk-factor considerations allow practitioners to tailor the treatment to the appropriate patient as opposed to broadly recommending patients for one treatment strategy over the other. Of course, there will always be extremists who fall on one side of this debate or the other.

Do you anticipate changes in the CMS (Centers for Medicare and Medicaid Services) reimbursement policy as a result of these data? Specifically, do you expect a decision in favor of covering asymptomatic patients treated with carotid stenting?

A revised CMS guidelines document is expected very soon and has been endorsed by the surgical, cardiology and radiology societies. These guidelines are likely to be “stent neutral” in terms of allowing reimbursement for this treatment. I believe the guidelines will be in line with the CREST results, which direct practitioners to tailor the treatment to the particular patient’s risk profile. However, I do not think that CREST by itself will be enough to push the CMS to reimburse CAS procedures.

As for carotid stenting in asymptomatic patients, the risk for this subgroup was very low, at < 3% (2.5% for stenting; 1.4% for surgery). Thus, CREST was well below the 3% limit that the expert consensus panel recommended. As a result, I do not see why asymptomatic patients who are at risk for stroke would not be considered for either CEA or CAS. I am also comfortable with those who argue for medical therapy in these patients, but I see a steady stream of patients with 90% carotid stenoses referred to me by other physicians who say: “I don’t want my patient to have a major stroke, please fix this...”. There is no evidence from CREST that would discourage the CMS from reimbursing for carotid stenting procedures in these asymptomatic patients. The benefit of CAS for asymptomatic patients has been proven in randomized, controlled trials — though some are a bit dated (1990s), but that is not a reason for the CMS to decide that it is no longer appropriate to treat patients with asymptomatic carotid disease. I do think it would be reasonable to conduct another trial to compare this, but it would be arbitrary, capricious and overall harmful for the CMS to deny asymptomatic patients coverage for CAS.

Can you evaluate the relative weight of these findings:
– That patients > 70 years of age seemed to fare better with endarterectomy, and younger patients did slightly better with stenting?

It was shown to be true in CREST that patients > 70 years of age did slightly better with CEA, and those < 70 years of age did slightly better with CAS. CREST is not the only trial in which this was proven to be the case; the large European SPACE trial (Stent-Protected Angioplasty versus Carotid Endarterectomy) reached the same conclusions in this regard. There is no clear explanation for these results, but these data are real and consistent. My guess is that as people age, their lesions have more calcium and become more tortuous, thus rendering them less attractive candidates for carotid stenting. On the other hand, younger patients’ lesions are much softer, straighter and easier to navigate with a stent. And surgery outcomes seem to remain fairly consistent across the board.

– That there were more minor strokes in the carotid stenting group and more MIs in the endarterectomy group:

Minor strokes — which could be as benign as numbness in the finger up to 30 days or so post procedure — were more frequent in in the stenting group, while the incidence of major stroke was the same in both CAS and CEA treatment arms. The incidence of MI was greater in the CEA arm (2.3% for CEA versus 1.1% for CAS). On the other side of that is the fact that a perioperative MI with vascular surgery carries with it a three- to four-fold increase in death over the next several years. Thus the prognosis of an MI at the time of CEA is not very good. As a result, we do not want to be in the position of arguing about which complication a patient would rather have. Instead, we want to try to determine which patients have the least chance of a complication with a particular treatment, and offer the patient that option. And in the case of asymptomatic patients, if one comes along who is not a good candidate for either CEA or CAS, then it may be best not to treat that patient. However, I would not deny asymptomatic patients with critical lesions the opportunity for revascularization, which was proven in the 1990s to be better than medical therapy. It is true that medical therapy has undergone improvements, but it has not been proven that it is better than revascularization. And the real problem is that the first stroke a patient suffers is often his/her last stroke; it’s not a good idea to “wait and see what happens”, because that first symptom, in about half the cases, is a stroke.

The difference between CREST and the European SPACE trial was the training requirements for the stenting operators. In both CREST and SPACE, the surgeons were held to very high standards, requiring a certain volume of cases, a < 3% complication rate in their asymptomatic patients, and so forth. They had to prove that they were skilled, experienced surgeons. In the CREST trial, the investigators had to go through a lead-in phase and be “blessed” by a committee in order to participate. In the European trials, however, relative novices were allowed to perform CAS. In fact, in the recently published ICSS (International Carotid Stenting Study), one site reported 5 major strokes. Thus, experience and skill are paramount when it comes to treatment of carotid stenosis, whether at the hands of a surgeon or an interventional cardiologist.

How long will these patients be followed?

The CREST trial patients will be followed out to ten years, which will provide excellent data on the durability of these treatments. The current CREST report reflects the first four years.

In your view, will carotid artery stenting finally occupy the place many interventionists believe it should in the management of
patients with carotid stenosis?

Much progress has been made in the field since CREST was launched. New safer, more effective equipment has been introduced since the CREST trial. Some of the devices we used in CREST are no longer used today. Proximal protection devices such as the Mo.Ma (Invatec/Medtronic, Inc., Minneapolis, Minnesota) and the Gore flow reversal system (W.L. Gore & Associates, Inc., Flagstaff, Arizona) have revolutionized carotid stenting. We just published a paper last month in JACC involving 1,300 consecutive patients with an overall stroke rate of 1.6% and a < 1% stroke rate in asymptomatic patients. Thus, with these kinds of results, the pendulum will be swinging toward a less invasive approach to treatment of carotid disease, continuing with the relentless push to minimize open surgery where possible. Today, a growing number of vascular surgeons are being trained to perform endovascular carotid stenting procedures, thereby reducing the competition between surgeons, interventional cardiologists and interventional radiologists. L. Nelson Hopkins is a perfect example of this crossover: he can perform open surgery or place a stent to treat carotid stenosis, depending on what is best for his patient. Non-surgical options are rapidly advancing across the board in medicine today for obvious reasons: they are more beneficial and patient-friendly and cost less. And let’s not forget that with CEA, there is the risk of complications such as cranial nerve problems, hematoma, infection and so forth in 4–6% of patients.

Dr. Christopher J. White graduated AOA from Case Western Reserve University and completed his specialty training in Internal Medicine and Cardiology at Letterman Army Medical Center in San Francisco in 1983. Dr. White is Board certified in Internal Medicine, Cardiovascular Diseases and Interventional Cardiology. He has been elected to Fellowship in the American College of Cardiology, the American Heart Association, the European Society of Cardiology, the Society of Vascular Medicine and Biology, and the Society of Cardiac Angiography and Interventions. He is Editor-in-Chief of the most prestigious medical journal in invasive cardiology, Catheterization and Cardiovascular Interventions. He is Co-Director of “Peripheral Angioplasty and All That Jazz”, now in its 13th year, one of the largest live-demonstration courses for Cardiologists wishing to learn more about the endovascular management of peripheral arterial disease. He has authored more than 250 manuscripts and abstracts, five books, and 43 book chapters. His expertise includes non-surgical treatment of coronary and peripheral vascular diseases, including coronary stents, carotid stents, peripheral vascular angioplasty, laser therapy, valvuloplasty, brachytherapy, limb salvage, renal stents and stroke therapy.