Medical Versus Surgical Treatment of Asymptomatic Carotid Stenosis
The Ever-Changing Nature of Evidence-Based Medicine
Randomized trials have shown that prophylactic carotid endarterectomy (CEA) in patients with asymptomatic carotid stenosis (ACS) moderately reduces stroke risk compared with medical management alone provided that the procedural morbidity and mortality does not exceed 3%. These results provided “evidence-supported” armor to increasingly perform CEA on patients with ACS despite opposition questioning the marginal benefit from surgery and its cost-effectiveness. These trials were conducted in the 1980s to early 2000s, a time when aspirin was the sole antiplatelet therapy, and before the emergence of statins, angiotensin-converting enzyme inhibitors, and new antihypertensive agents. Medical therapy has changed dramatically since, and the annual rates of stroke in medically treated patients with ACS have fallen from 2% to 2.5% to <1% in recent years with the advent of modern medical therapy and its increased use, improved management of vascular risk factors, and decline in smoking.1,2 Conversely, stroke risk after carotid revascularization remained unchanged over the last 2 decades.
That medical treatment is now as effective as CEA in the majority of patients with ACS is no longer a subject of controversy and is agreed on by our opponents. Current estimates suggest that only 5% of patients with ACS stand to benefit from CEA in the era of modern medical polytherapy with antiplatelets, statins, and angiotensin-converting enzyme inhibitors. So, who might benefit from CEA? The premise of a “test” to identify patients with ACS at high risk for stroke who would benefit from prophylactic CEA has allured us for years. Several candidates have been proposed such as advanced imaging of plaque morphology and content and assessment of cerebral vasomotor reactivity and reserve. Two recent studies suggest that the use of transcranial Doppler to detect embolic signals might be particularly useful in stratifying patients with ACS who would benefit from surgery.3,4 Interestingly, the rate of progression of carotid stenosis and the detection of emboli declined with intensive medical polytherapy over time in 1 study,3 suggesting stabilization of carotid plaques and that emboli monitoring might be useful to assess the therapeutic efficacy of medical therapy and to adjust it accordingly. Although these results are promising, further larger-scale studies are needed before emboli monitoring can be recommended for clinical decision-making. In the Asymptomatic Carotid Emboli Study (ACES), only 16% of patients with ACS had embolic signals on baseline transcranial Doppler, and only 13% of them had ipsilateral strokes during a 2-year follow-up period. Strokes in patients with ACS may be related to artery-to-artery embolism secondary to plaque ulceration and rupture, low flow related to luminal narrowing, or impaired vasomotor reactivity in the distal vascular bed, especially when collateral flow is impaired. The usefulness of emboli monitoring in the subgroup of patients with ACS who may develop strokes through the latter mechanisms is uncertain.
ACS patients' comorbid conditions and characteristics are perhaps the best predictors of stroke risk with medical versus surgical treatments. Previous studies suggest that the benefit of surgery is greater in men aged ≤74 years; is questionable in high-surgical risk patients given increased procedural morbidity and mortality; and is largely unproven in women. These factors should be considered when selecting patients with ACS for CEA along with life expectancy, the operator's complication rates, and the patient's preference. In our view, it is reasonable to recommend CEA in young patients with moderately high-grade ACS whose life expectancy is at least ≥5 years, especially men, and in those in whom the degree of carotid stenosis significantly progresses despite “best” medical care and therapy. Because strokes in patients with ACS may not always be heralded by a transient ischemic attack, an important cornerstone of medical treatment should be to educate patients about stroke warning symptoms and signs and to advise them to seek urgent medical attention should they develop symptoms.
Our invited authors did not directly comment on the role of carotid stenting in ACS. The Carotid Revascularization Endarterectomy Versus Stenting Trial (CREST) included 1181 patients with ACS. Although the trial did not randomize a group of patients with ACS to medical therapy without CEA or stenting, the rates of procedural stroke or death were similar for stenting and CEA at approximately 3.5% suggesting that the benefit of carotid stenting over modern medical therapy in unselected patients with ACS is also unproven at this time.
Our experts comment on the need to include a treatment arm of modern medical therapy in future trials examining CEA and stenting in patients with ACS to confirm that medical treatment alone is the most appropriate. This would be certainly helpful, but is it necessary? Robust evidence indicates that current medical therapy has led to a lower stroke risk, whereas the risk of stroke with revascularization has remained unchanged, if not increased, due to the aging of our patients and increasing comorbidities. The stroke rates in patients with ACS are now equal to or lower than the stroke rates for patients treated with carotid angioplasty and stenting or CEA in almost all recent trials. Yesterday's evidence is today's lack of it!
The opinions expressed in this article are not necessarily those of the editors or of the American Heart Association. This article is Part 3 in a 3-part series. Parts 1 and 2 appear on pages 1152 and 1154, respectively.
- Received January 13, 2011.
- Accepted January 21, 2011.
- © 2011 American Heart Association, Inc.
- Marquardt L,
- Geraghty OC,
- Mehta Z,
- Rothwell PM
- Abbott AL