Reply

Abstract

We appreciate the comments from Mr. Adiseshiah regarding the study population and data presented in the recent CaRESS trial article.¹ Mr. Adiseshiah correctly notes that the CaRESS study is not a randomized trial and thus does not provide Level 1 evidence on the subject of carotid artery stenting (CAS) versus carotid endarterectomy (CEA); we noted this as a limitation of the study.¹ Indeed, we were careful to describe the CaRESS trial as a prospective, nonrandomized, comparative cohort study of a broad-risk population of patients with carotid stenosis. In accord with the parlance of levels of evidence,² this would qualify the data as Level 2 evidence.

The unique feature of the CaRESS trial is the inclusion of a broad-risk population of patients as would be expected in usual clinical practice. This encompasses both low- and high-risk patients. The results for both groups of patients were favorable, indicating that similar low stroke/death rates can be achieved using either CEA or CAS. Although the numbers were small, we found no difference in the outcome based on symptom status of the patients, which is in contrast to published reports of higher stroke/death rates in both the CAS and CEA arms of prospective randomized studies.^3,4 With regard to the numbered points:

We chose not to include confidence intervals in the manuscript because they did not contribute additional knowledge given that the standard errors were provided. The 95% confidence intervals for the composite endpoints of death/stroke/MI (CAS: 14.38% to 29.08%; CEA: 20.62% to 33.36%) and death/stroke (CAS: 14.45% to 29.23%; CEA: 20.07% to 32.89%), as well as individual events such as all-cause mortality, stroke, and MI, were quite reasonably narrow. Thus, the data do justify the assumption of equivalence. We believe our study design and statistical methods were sound and would have revealed differences had there been any.

We stated in the CaRESS article that the study was designed to include both symptomatic and asymptomatic patients to be consistent with usual clinical practice patterns. Therefore, it is not appropriate to consider symptomatic patients as “confounders.” Symptomatic patients made up only one third of the overall population, as was the case in the SAPPHIRE (Stenting and Angioplasty with Protection in Patients at High Risk for Endarterectomy) prospective randomized trial.³ As can be seen in Table 5 of the article,¹ the 4-year rate of the composite endpoint death/stroke/MI, for example, was higher in the symptomatic CEA patients compared with asymptomatic CEA patients; the opposite was true for CAS: asymptomatic CAS patients had a higher composite event rate compared with symptomatic CAS patients at 4 years.

We agree that published Level 1 evidence from the 1990s shows that the outcome of CEA is superior to best medical treatment for both symptomatic^5,6 and asymptomatic⁷ patients. However, the CaRESS trial did not include a best medical treatment arm.

We agree that, unlike CEA, there is no Level 1 study addressing CAS compared to best medical therapy, but it is important to note that the CaRESS study was designed to compare only two interventions, CEA and CAS.

We used the term “broad risk” to include the spectrum of patients encountered in usual clinical practice, including patients who were either (a) symptomatic with ≥50% carotid artery stenosis or (b) asymptomatic with ≥75% carotid artery stenosis. The term “broad risk” as defined in the protocol was specified in the 30-day and 1-year CaRESS publications,^8,9 which were referenced in the 4-year article. The term “non–high-risk” was used to differentiate patients based upon the Centers for Medicare and Medicaid Services criteria for “high risk,” which appears in the current National Coverage Determination¹⁰ and was explained and referenced in the 4-year study.

We disagree that the International Carotid Stenting Study (ICSS) presentation at this year's European Stroke Conference is “Level 1 evidence” since it is not a published article. While the presentation is interesting, it does not qualify as Level 1 evidence until the data have withstood peer review and been published.

Our conclusions that there were no significant differences in short- or long-term (4-year) stroke, death, or stroke/death rates between patients treated with CAS or CEA under conditions described in this prospective study is supported by the data presented. We believe these conclusions should be accepted as such. We have made no claim that this represents Level 1 evidence, and we, along with the clinical community, await such evidence.

References

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. Carotid Revascularization Using Endarterectomy or Stenting Systems (CaRESS): 4-year outcomes. J Endovasc Ther. 2009;16:397–409.

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. Evidence Based Medicine: How to Practice and Teach EBM, 2nd ed. New York: Churchill Livingstone; 2000.

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. Protected carotid-artery stenting versus endarterectomy in high-risk patients. N Engl J Med. 2004;351:1493–1501.

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. EVA-3S investigators. Endarterectomy Versus Angioplasty in Patients with Symptomatic Severe Carotid Stenosis (EVA-3S) trial: results up to 4 years from a randomised, multicentre trial. Lancet Neurol. 2008;7:885–892.

Beneficial effect of carotid endarterectomy in symptomatic patients with high-grade carotid stenosis. North American Symptomatic Carotid Endarterectomy Trial Collaborators. N Engl J Med. 1991;325:445–453.

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. Benefit of carotid endarterectomy in patients with symptomatic moderate or severe stenosis. North American Symptomatic Carotid Endarterectomy Trial Collaborators. N Engl J Med. 1998;339:1415–1425.

Endarterectomy for asymptomatic carotid artery stenosis. Executive Committee for the Asymptomatic Carotid Atherosclerosis Study. JAMA. 1995;273:1421–1428.

CARESS Steering Committee. Carotid Revascularization using Endarterectomy or Stenting Systems (CARESS): phase I clinical trial. J Endovasc Ther. 2003;10:1021–1030.

CARESS Steering Committee. Carotid Revascularization Using Endarterectomy or Stenting Systems (CaRESS) phase I clinical trial: 1-year results. J Vasc Surg. 2005;42:213–219.

10.

Centers for Medicare and Medicaid Services. Percutaneous transluminal angioplasty (PTA) of the carotid artery concurrent with stenting (CAG-00085R3). Publication 100-03 Medicare National Coverage Determinations. December 24, 2008. Available at: http://www.cms.hhs.gov/transmittals/downloads/R98NCD.pdf. Last accessed September 25, 2009.