Revascularization of Asymptomatic High-Grade Stenosis Is Not Indicated With Contemporary Stroke Prevention Medical Therapy
The American Stroke Association Guidelines for Primary Prevention of Stroke state that for patients with asymptomatic carotid artery stenosis, “the advantage of revascularization over current medical therapy alone is not well established.” So, what is the evidence related to the management of asymptomatic high-grade carotid artery stenosis (AHGCAS), and why should we interpret this evidence to conclude that contemporary medical therapy alone is the preferred treatment to reduce ipsilateral stroke risk? Three studies, the Asymptomatic Carotid Atherosclerosis Study (ACAS), the Medical Research Council (MRC) Asymptomatic Carotid Surgery Trial, and the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST), have documented 5-year risks of periprocedural complications and subsequent stroke among patients with AHGCAS treated with revascularization of 5.1%, 6.4%, and 4.6% (estimated), respectively. Conversely, the ACAS and MRC studies documented 5-year risks of stroke for patients with AHGCAS treated with medication alone of 11.0% and 11.8%, resulting in an absolute risk reduction in ipsilateral stroke of approximately 1% per annum for patients treated with revascularization.
Although the 5-year risk of periprocedural complications and subsequent stroke associated with revascularization of AHGCAS has remained relatively stable at approximately 5% over the last 20 years, there is mounting evidence that, over the same time period, improvements in stroke prevention medical therapy have resulted in a significant reduction in the risk of ipsilateral stroke in patients with AHGCAS who are not revascularized. Over the last decade, subsequent to the ACAS and MRC studies, patients with AHGCAS have been routinely treated with contemporary risk factor-modifying medications such as angiotensin-converting enzyme inhibitors and statins, which have been shown to significantly reduce the risk of stroke in patients with vascular risk factors. Given that the treatment effect of carotid revascularization in patients with AHGCAS is only modest at best, a small reduction in the risk of stroke in patients with AHGCAS treated with medications alone will negate the stroke risk reduction benefit associated with revascularization. Between 2002 and 2009, the Oxford Vascular Study evaluated 1153 patients with stroke and transient ischemic attack and found ultrasound evidence of AHGCAS ≥50% in 101 patients.1 All patients were treated with antiplatelet medication, a statin, and medications to manage diabetes or hypertension if clinically indicated, and the study found an annual rate of ipsilateral stroke among the patients with AHGCAS of only 0.34% (95% CI, 0.01 to 1.87). In addition, Abbott's elegant review of the impact of medical management on the risk of stroke associated with AHGCS2 documented a decline in the annual rate of ipsilateral stroke from 2.5% to 1.1% between 1985 and 2007 for patients treated with medication alone. These stroke rates are now, equal to, or lower than the stroke rates for patients treated with revascularization in the ACAS, MRC, and CREST studies.
However, even if we can demonstrate that contemporary medical therapy alone is more effective than revascularization in reducing the risk of ipsilateral stroke in patients with AHGCAS, some patients (and their physicians) will still be concerned about having a stroke and will want their stenosed carotid artery revascularized. It would be helpful for both patients and clinicians if we could stratify stroke risk in patients with AHGCAS and identify which patients, if any, would benefit from revascularization. Unfortunately, there are currently no reliable predictors of increased ipsilateral stroke risk in patients with AHGCAS. Transcranial Doppler detection of asymptomatic emboli and assessment of cerebrovascular reserve with acetazolamide both show promise as investigations that could stratify stroke risk in patients with AHGCAS. Other potential predictors of ipsilateral stroke risk in patients with AHGCAS include plaque morphology, younger age, and the presence of serum inflammatory biomarkers. However, none of these predictors has been shown to reliably predict ipsilateral stroke risk in patients with AHGCAS, and further studies are needed before any of these predictors can be used routinely to identify patients with AHGCAS who will benefit from revascularization instead of being treated with medical therapy alone.
Finally, although there is compelling data to support the use of medical therapy alone to reduce the risk of ipsilateral stroke in patients with asymptomatic high-grade carotid artery stenosis, additional studies are required to confirm that this intervention alone is the most appropriate treatment for these patients. The CREST investigators are planning on performing such a study (Thomas Brott, MD, personal communication), and they will hopefully receive funding to conduct this important clinical trial.
The opinions expressed in this article are not necessarily those of the editors or of the American Heart Association. This article is Part 2 in a 3-part series. Parts 1 and 3 appear on pages 1152 and 1156, respectively.
- Received January 1, 2011.
- Revision received February 4, 2011.
- Accepted February 10, 2011.
- © 2011 American Heart Association, Inc.
- Marquardt L,
- Geraghty OC,
- Mehta Z,
- Rothwell PM
- Abbott AL