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Asymptomatic carotid artery disease: A personalized approach to management

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ABSTRACTAsymptomatic carotid artery disease is relatively common and poses a challenge for internists as well as vascular specialists when deciding whether to pursue surgical endarterectomy, percutaneous stenting, or medical therapy alone. The authors review the management of asymptomatic carotid disease, reflecting the most current data.

KEY POINTS

  • Current guidelines are based on outdated data that may not represent the best evidence regarding the management of asymptomatic carotid disease.
  • Stroke is a devastating outcome of carotid disease, and most patients and physicians are wary of deferring revascularization until a stroke occurs.
  • Given the inherent risk associated with revascularization (endarterectomy or stenting) and the paucity of data, the approach should be personalized on the basis of life expectancy, sex, risk factors for stroke, and clinical acumen.
  • Future research should focus on noninvasive tools to determine which patients are at high risk of stroke and may benefit from revascularization.


 

References

Carotid artery disease that is asymptomatic poses a dilemma: Should the patient undergo revascularization (surgical carotid endarterectomy or percutaneous stenting) or receive medical therapy alone?

On one hand, because one consequence of carotid atherosclerosis—ischemic stroke—can be devastating or deadly, many physicians and patients would rather “do something,” ie, proceed with surgery. Furthermore, several randomized trials1–4 found carotid endarterectomy superior to medical therapy.

On the other hand, these trials were conducted in the 1990s. Surgery has improved since then, but so has medical therapy. And if we re-examine the data from the trials in terms of the absolute risk reduction and number needed to treat, as opposed to the relative risk reduction, surgery may appear less beneficial.

Needed is a way to identify patients who would benefit from surgery and those who would more likely be harmed. Research in that direction is ongoing.

Here, we present a simple algorithmic approach to managing asymptomatic carotid artery stenosis based on the patient’s age, sex, and life expectancy. Our approach is based on a review of the best available evidence.

UP TO 8% OF ADULTS HAVE STENOSIS

Stroke is the third largest cause of death in the United States and the leading cause of disability.5 From 10% to 15% of strokes are associated with carotid artery stenosis.6,7

The prevalence of asymptomatic carotid disease, defined as stenosis greater than 50%, ranges from 4% to 8% in adults.8

Recommendations for screening for asymptomatic carotid artery stenosis

However, major societies recommend against screening for carotid stenosis in the general population.9–12 Similarly, the US Preventive Services Task Force also discourages the use of carotid auscultation as screening in the general population (Table 1).13 Generally, cases of asymptomatic carotid stenosis are diagnosed by ultrasonography after the patient’s physician happens to hear a bruit during a routine examination, during a preoperative assessment, or after the patient suffers a transient ischemic attack or stroke on the contralateral side.

CLASS II RECOMMENDATIONS FOR SURGERY OR STENTING

There are well-established guidelines for managing symptomatic carotid disease,14 based on evidence from the North American Symptomatic Carotid Endarterectomy Trial15 and the European Carotid Surgery Trial,16 both from 1998. But how to manage asymptomatic carotid disease remains uncertain.

If stenosis of the internal carotid artery is greater than 70% on ultrasonography, computed tomography, or magnetic resonance imaging, and if the risk of perioperative stroke and death is low (< 3%), current guidelines14 give carotid endarterectomy a class IIa recommendation (ie, evidence is conflicting, but the weight of evidence is in favor), and they give prophylactic carotid artery stenting with optimal medical treatment a class IIb recommendation (efficacy is less well established).5

But medical management has improved, and new data suggest that this improvement may override the minimal net benefit of intervention in some patients.17 Some authors suggest that it is best to use patient characteristics and imaging features to guide treatment.18

EVIDENCE TO SUPPORT CAROTID REVASCULARIZATION

Landmark trials in asymptomatic carotid stenosis

Three major trials (Table 2) published nearly 20 years ago provide the foundation of the current guidelines:

  • the Endarterectomy for Asymptomatic Carotid Atherosclerosis Study (ACAS)1
  • the Asymptomatic Carotid Surgery Trial (ACST)2,3
  • the Veterans Affairs (VA) Cooperative Study.4

A Cochrane review of these trials,19 where medical therapy consisted only of aspirin and little use of statin therapy, found that carotid endarterectomy reduced the rate of perioperative stroke or death or any subsequent stroke in the next 3 years by 31% (relative risk 69%, 95% confidence interval [CI] 0.57–0.83). “Perioperative” was defined as the period from randomization until 30 days after surgery in the surgical group and an equivalent period in the medical group.

Moreover, carotid endarterectomy reduced the rate of disabling or fatal nonperioperative stroke by 50% compared with medical management alone.1,2,19 Patients who had contralateral symptomatic disease or who had undergone contralateral carotid endarterectomy seemed to benefit more from the procedure than those who had not.19

Also, the ACST investigators found that revascularization was associated with a reduction in contralateral strokes (which occurred in 39 vs 64 patients, P = .01) independent of contralateral symptoms or contralateral carotid endarterectomy.2,3 The exact mechanism is unknown but could be related to better blood pressure control and risk factor modification after carotid endarterectomy.

Another factor supporting revascularization is that the outcomes of revascularization have improved over time. In 2010, the Carotid Revascularization Endarterectomy Versus Stenting Trial (CREST)20 reported a 30-day periprocedural incidence of death or stroke of only 1.4%, compared with 2.9% in the earlier landmark trials.

Stenting is a noninferior alternative

For patients who have asymptomatic stenosis greater than 80% on color duplex ultrasonography and a risk of stroke or death during carotid endarterectomy that is prohibitively high (> 3%), carotid stenting has proved to be a noninferior alternative.21,22

The Stenting and Angioplasty With Protection of Patients With High Risk for Endarterectomy (SAPPHIRE) trial21 reported a risk of death, stroke, or myocardial infarction of about 5% at 30 days and 10% at 1 year after stenting. A recent observational study revealed lower perioperative complication rates, with a risk of death or stroke of about 3%, which satisfy current guideline requirements.23

To be deemed at high surgical risk and therefore eligible for the SAPPHIRE trial,21 patients had to have clinically significant cardiac disease, severe pulmonary disease, contralateral carotid occlusion, contralateral laryngeal-nerve palsy, recurrent stenosis after carotid endarterectomy, previous radical neck surgery or radiation therapy to the neck, or age greater than 80.

EVIDENCE AGAINST CAROTID REVASCULARIZATION

Although carotid revascularization has evidence to support it, further interpretation of the data may lessen its apparent benefits.

Small absolute benefit, high number needed to treat

If we compare the relative risk reduction for the outcome of perioperative death or any stroke over 5 years (30% to 50%) vs the absolute risk reduction (4% to 5.9%), revascularization seems less attractive.19

Relative risk reduction in death or stroke with carotid surgery is 30%–50%; absolute risk reduction is 4%–5.9%

The benefit may be further diminished if we consider only strokes related to large vessels, since up to 45% of strokes in patients with carotid disease are lacunar or cardioembolic.24 Assessing for prevention of large-vessel stroke using the ACAS data, the benefit of carotid endarterectomy for prevention of stroke is further decreased to a 3.5% absolute risk reduction, and the number needed to treat for 2 years increases from 62 to 111.24,25 Nevertheless, revascularization is necessary in appropriately selected patients, as a cerebrovascular event can cause life-altering changes to a patient’s cognitive, emotional, and physical condition.26

Medical therapy—and surgery—are evolving

The optimal medical management used in the landmark studies was significantly different from what is currently recommended. The ACAS trial18 used only aspirin as optimal medical management, with no mention of statins. In the ACST trial,2,3 the use of statins increased over time, from 7% to 11% at the beginning of the trial to 80% to 82% at the end.

On the other hand, the ACAS1 surgeons were required to have an excellent safety record to participate. This might have compromised the trial’s validity or our ability to generalize its conclusions.

Recent data from Abbott17 suggested a loss of a statistically significant surgical advantage in prevention of ipsilateral stroke and transient ischemic attack from the early 1990s. This is most likely explained by improved medical therapy, since there was a 22% increase in baseline proportion of patients receiving antiplatelet therapy from 1985 to 2007, with 60% of patients taking antihypertensive drugs and 30% of patients taking lipid-lowering drugs. Moreover, since 2001, the annual rates of ipsilateral stroke in patients receiving medical management alone fell below those of patients who underwent carotid endarterectomy in the ACAS trial.

The analysis by Abbott17 has major limitations: inclusion of small studies, many crossover patients, and heterogeneity. In support of this allegation, a small trial (33 patients) reported a risk of stroke ipsilateral to an asymptomatic carotid stenosis as low as 0.34% per year.25 Even when contrasting the outcomes of medical therapy against those of current carotid endarterectomy, in which the rate of perioperative stroke and death have fallen to 0.88% to 1.7%,17,27,28 there is concern that the risk associated with surgery may outweigh the long-term benefit.

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