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(Stroke. 2002;33:2519.)
© 2002 American Heart Association, Inc.

Controversies in Stroke

Angioplasty and Stenting Should Be Performed Only in the Setting of a Clinical Trial

Thomas G. Brott, MD

From the Mayo Clinic, Jacksonville, Florida.

Correspondence to Thomas G. Brott, MD, Mayo Clinic, 4500 San Pablo Rd, Jacksonville, FL 32224. E-mail brott.thomas{at}mayo.edu

Key Words: carotid endarterectomy • clinical trials • outcome • stents

Dr Roubin cites exciting observational data supporting carotid artery stenting as treatment for focal carotid artery disease. Unfortunately, observational studies cannot substitute for randomized trials.¹ The design is not experimental. The treatment for each patient is chosen by the interventionalist, and so selection bias cannot be avoided. Assessment of outcomes is vulnerable to investigator ascertainment bias and in some cases conflict of interest. Full reporting cannot be ensured, nor can publication bias be avoided. Comparison to historical controls is not valid because the competing medical and surgical treatments have advanced.

For surgical therapy, randomized trials have shown that absolute risk reduction may be high as 5% per year for symptomatic patients with stenosis 70%,^2,3 approximately 1% per year for symptomatic patients with stenosis 50% to 69%,³ and up to 1% per year in asymptomatic patients with stenosis 60%, when surgical results are optimal.⁴ Benefits for asymptomatic women following CEA have not been established, and CEA has not been compared with medical treatments as currently recommended (eg, antihypertensive therapy for blood pressure 135 mm Hg systolic, 85 mm Hg diastolic; lipid-lowering therapy for diet-resistant LDL >100 mg/dL; alternative antiplatelet therapy for aspirin failure).⁵

For carotid stenting, safety and efficacy (and durability) as first-choice treatment have not been established for low-risk patients. For such patients, those who would have been eligible for NASCET or ACAS, carotid stenting must be considered experimental. CEA is the standard of care. Accordingly, carotid stenting should be done in the context of a clinical trial protocol, patient informed consent, and oversight of institutional review boards. Interventionalist-reported case series cannot justify stenting for low-risk patients, even those reporting outstanding results.⁶ The more generalizable prospective, multicenter trial experience as of 2002 does not suggest low morbidity and mortality.^7–9 In CAVATAS, stroke lasting more than 7 days, intracerebral hemorrhage, or death within 30 days occurred in 6 patients among the 55 who were treated with carotid stenting.⁹ In the WALLSTENT trial, stroke or death occurred within 30 days in 12%.

For high-risk symptomatic patients, stenting has the potential advantage of being less invasive. In addition, patients with high cervical stenoses, radiation-induced stenoses, and post-CEA stenoses are technically more challenging for the surgeon. Nonetheless, observational data are not sufficient to proceed with stenting as first-choice treatment. Studies of CEA for high-risk patients, those who would not have qualified for NASCET, have reported perioperative stroke and death rates equivalent to those reported for stenting.¹⁰ A safety advantage for carotid stenting compared with CEA has not been shown for any high-risk comorbidity.

High-risk asymptomatic patients are better off with medical therapy until proven otherwise (ie, in a randomized clinical trial). A "need" for carotid revascularization has not been empirically established in these patients. Periprocedural risk is 3% to 5% in the best of hands.¹¹ No evidence exists to suggest that carotid stenting is superior to 2002 medical therapy, eg, for the asymptomatic 82-year-old diabetic male, the 72-year-old asymptomatic female with cardiomyopathy, or the asymptomatic patient with restenosis.

What, then, are the indications for carotid stenting outside a clinical trial? A positive evidence-based recommendation cannot be sustained. But, much of what we do in medicine is not supported by evidence from randomized clinical trials.¹ For some of the special cases mentioned above (symptomatic patients with postirradiation stenosis, post-CEA stenosis, high cervical stenosis, stenosis with contralateral occlusion, or stenosis with need for coronary revascularization), randomized trials may not be feasible. Carotid stenting may be considered—for symptomatic patients—by centers with unassailable excellent results.

Is it ethical to study carotid stenting in clinical trials, or are the patients of 2002 being used as guinea pigs to benefit the patients of 2012? The success of coronary artery stenting and the observational evidence Dr Roubin cites do offer the rationale and the ethical support for randomized clinical trials. However, these trials must protect patients by including only interventionalists with demonstrated low morbidity and mortality, comparable to that of the surgeons. Once under way, these trials must be monitored frequently to ensure that the low rates of morbidity and mortality are reproduced within the scrutiny of the trial. In addition, investigators should have mechanisms in place for evaluating new technology, such as the distal embolization capture devices now being touted,¹² or new drugs, such as the GPllbllla platelet aggregation receptor antagonists.¹³

Footnotes

The opinions expressed in this editorial are not necessarily those of the editors or of the American Stroke Association.

References

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