Current Cardiology Reports

, Volume 14, Issue 2, pp 125–134

Management of Combined Severe Carotid and Coronary Artery Disease

Authors

    • Interventional Cardiology Unit, Division of CardiologyUniversity Hospital
  • Flavio Ribichini
    • Department of Medicine, Catheterisation LaboratoriesUniversity of Verona
    • Cardiovascular Interventional Unit
  • Fausto Castriota
    • GVM Care and Research, Interventional Cardio-Angiology Unit
    • Maria Cecilia Hospital—GVM Care and Research Cotignola
  • Alberto Cremonesi
    • GVM Care and Research, Interventional Cardio-Angiology Unit
    • Maria Cecilia Hospital—GVM Care and Research Cotignola
Peripheral Vascular Disease (M Shishehbor, Section Editor)

DOI: 10.1007/s11886-012-0246-1

Cite this article as:
Roffi, M., Ribichini, F., Castriota, F. et al. Curr Cardiol Rep (2012) 14: 125. doi:10.1007/s11886-012-0246-1
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Abstract

Patients with severe carotid and coronary disease—especially if they require coronary artery bypass grafting (CABG)—are at high risk of cardiac events and stroke. Carotid revascularization should be considered for patients with symptomatic carotid disease and bilateral severe asymptomatic carotid stenosis. In patients with unilateral asymptomatic carotid stenosis, decision to proceed to revascularization should be based more on a perspective of long-term stroke prevention than of perioperative stroke reduction. Compared with endarterectomy, carotid artery stenting is associated with a lower incidence of periprocedural myocardial infarction, an event linked to long-term mortality. This observation may be particularly relevant for patients with advanced coronary artery disease such as those undergoing CABG. Irrespective of the carotid revascularization strategy, a broad disease management approach based on lifestyle modification and pharmacologic cardiovascular prevention is more likely to affect both the quality and duration of life than revascularization itself.

Keywords

Carotid artery diseaseCoronary artery diseaseCoronary artery bypass graftingCarotid endarterectomyCarotid artery stentingPerioperative strokeStroke preventionPerioperative myocardial infarctionMultilevel arterial disease

Introduction

Multisite artery disease defines the presence of atherosclerotic disease at two or more vascular territories. Although patients with multisite artery disease are commonly encountered in clinical practice, their management is supported by limited data because those high-risk patients have usually been excluded from randomized trials. The Reduction of Atherothrombosis for Continued Health (REACH) registry enrolled 68,236 outpatients with either established atherosclerotic arterial (ie, coronary, lower extremity, or cerebrovascular) disease or three or more cardiovascular risk factors [1]. The incidence of cardiovascular death, myocardial infarction (MI), stroke, or hospitalization for ischemic events at 3 years were 25.5% for patients with symptomatic vascular disease in one vascular site versus 40.5% for patients symptomatic in multiple vascular sites (P < 0.001) [2]. The management of one group of patients with multisite disease—those with severe carotid disease requiring coronary artery bypass grafting (CABG)—is particularly controversial [3, 4]. The article aims to review the evidence supporting various management strategies of patients with severe coronary and carotid artery disease as well as to describe the risk, mechanisms, and outcomes of perioperative stroke in patients undergoing CABG.

Carotid Artery Disease in Patients with Coronary Artery Disease: Prevalence and Value of Screening

The prevalence of asymptomatic carotid artery disease in the general population is low and influenced by age and gender. A meta-analysis of four population-based studies including 23,706 participants showed that the prevalence of carotid stenosis ≥50% ranged among men from 0.2% to 7.5% in individuals aged less than 50 years and ≥80 years, respectively. The corresponding values for women were less than 0.1% and 5.0%. The prevalence of carotid stenosis ≥70% ranged in men from 0.1% in individuals less than 50 years to 3.1% in those aged ≥80 years. For women, the corresponding prevalence rates of of carotid stenosis ≥70% were less than 0.1% and 0.9% [5]. Among patients with atherosclerotic disease, the prevalence of carotid disease varies depending on the additional territory involved. Among 2274 patients referred to a vascular center, the prevalence of an asymptomatic carotid stenosis ≥70% was 3.1% among patients with coronary artery disease (CAD), 8.8% among patients with abdominal aortic aneurysm, and 12.5% among patients with peripheral artery disease [6].

In patients with CAD, the prevalence of carotid artery disease differs to a great extent based on the population studied and the stenosis severity. Accordingly, a recent literature review reported that the prevalence of carotid stenosis ≥50% ranged between 1.9% and 20.7%, whereas the prevalence of stenosis ≥80% ranged between 5.0% and 6.0% [7]. Among patients screened for CABG, the prevalence of carotid stenosis ≥50% ranged between 10.3% and 22.3%, whereas for stenosis ≥80% the corresponding proportions ranged between 4.0% and 10.0% [7]. Among 1184 patients ≥65 years of age requiring CABG, the prevalence rates of carotid stenosis ≥50% and ≥80% were 17.0% and 5.9%, respectively [8]. Among patients with CAD, a risk score based on age, current smoking, and hypercholesterolemia allowed for identification of a high-risk group with a prevalence of carotid stenosis greater than 60% to as high as 35% [9].

Because of the lack of high-quality studies, the value of screening of carotid artery disease prior to CABG remains controversial. The 2011 American CABG guidelines state that duplex scanning is reasonable in selected patients who are considered to have high-risk features (ie, age ≥65 years, left main coronary stenosis, peripheral artery disease, history of transient ischemic attack [TIA] or stroke, hypertension, smoking, or diabetes mellitus) (Class IIa, level of evidence [LOE] C) [10]. The 2011 European peripheral artery disease guidelines recommend carotid duplex in the presence of history of cerebrovascular disease, carotid bruit, age ≥70 years, multivessel CAD, or peripheral artery disease (Class I, LOE B) [11•].

Stroke in Patients Undergoing Cardiac Surgery

Stroke—one of the most feared complications of CABG—is associated with increased mortality and major disability, as well as increased health care costs. In a prospective study including 13,897 patients undergoing isolated CABG, the overall incidence of perioperative stroke was 2.8% [12]. Among the 388 events detected, ischemic-embolic strokes accounted for 62% of events, whereas hypoperfusion was identified as the cause of stroke in 9% of the cases and 1% were hemorrhagic strokes. With respect to the timing, 45% of the embolic and 56% of hypoperfusion strokes occurred within the first postoperative day. Independent predictors of both embolic and hypoperfusion strokes included cardiopulmonary bypass time and postoperative atrial fibrillation [13].

The type of cardiac surgery also determines the risk of stroke. A prospective data collection on 16,184 consecutive patients undergoing cardiac surgery in Leipzig showed that although overall incidence of stroke was 4.6%, it varied between surgical procedures: CABG 3.8%; beating-heart CABG 1.9%; aortic valve surgery 4.8%; mitral valve surgery 8.8%; double or triple valve surgery 9.7%; and CABG and valve surgery 7.4% [14]. Variables that independently predicted perioperative stroke included history of cerebrovascular disease, peripheral vascular disease, diabetes, hypertension, previous cardiac surgery, preoperative infection, urgent operation, cardiopulmonary bypass time, need for intraoperative hemofiltration, and high transfusion requirement (Table 1). The Washington Hospital experience of 16,528 consecutive patients undergoing CABG detected a perioperative stroke rate of 2%. Predictors of postoperative stroke included chronic renal insufficiency, recent MI, previous cerebrovascular accident, carotid artery disease, hypertension, diabetes, age greater than 75 years, moderate/severe left ventricular dysfunction, low cardiac output syndrome, and atrial fibrillation [15]. Postoperative stroke was associated with higher in-hospital mortality (14% vs 2.7% for patients without stroke; P < 0.001) and longer hospital stay.
Table 1

Characteristics of increased risk of stroke (perioperative or long-term) in patients with carotid stenosis undergoing cardiac surgery

Neurologic presentation

Symptomatic carotid stenosis

Carotid lesion

Degree of stenosis severity

Plaque morphology

Progressive stenosis

Embolic signals on transcranial Doppler

Contralateral carotid stenosis/occlusion

Cerebrovascular factors

Isolate hemisphere

Intracranial microvascular disease

Ischemic lesions in the carotid territory

Clinical characteristics

Older age

History of TIA/stroke

Severe atherosclerosis of the ascending aorta/aortic arch

Peripheral artery disease

Atrial fibrillation

Hypertension

Diabetes

Heart failure/severe left ventricular dysfunction

Renal failure

Surgical factors

On-pump surgery

Prolonged cardiopulmonary bypass/aorta cross-clamping

Calcified aorta, atheromatous plaque in the aorta

Need for proximal anastomosis and side clamping of the aorta

Valve surgery, combined coronary and valve surgery

Redo surgery

TIA transient ischemic attack.

The Cleveland Clinic database of 45,432 isolated CABG performed over almost 30 years reported an overall stroke rate of 1.6%, with a slow decline over time despite increasing risk profile of the patients [16]. With respect to the timing of stroke, 40% occurred intraoperatively (ie, neurologic deficit present when the patient awoke from anesthesia) and 58% postoperatively (with a peak at 40 hours), and for the remaining cases the time of onset remained undetermined [16]. Risk factors common to both intraoperative and postoperative stroke were older age, smaller body surface area, previous stroke, preoperative atrial fibrillation, and on-pump CABG. History of peripheral or carotid artery disease doubled the risk of stroke in multivariate analysis. This study also outlined the devastating effects of perioperative stroke in patients undergoing CABG. Accordingly, patients who experienced a stroke had substantially worse hospital outcomes, even after propensity adjustment for preoperative factors, than patients with no neurologic deficit: 19% mortality versus 3.7%; 44% prolonged ventilation versus 15%; and 13% renal failure versus 4.3% [16]. Stroke patients required longer intensive care unit and hospital stay and the difference in mortality persisted at long-term follow-up.

Impact of Carotid Disease on Perioperative Stroke Risk

A recent meta-analysis of 26 series for a total of 2531 patients with carotid stenosis undergoing cardiac surgery reported that patients with a 50–99% stenosis or occlusion incurred a 7.4% stroke risk, increasing to 9.1% in those with 80–99% stenosis or occlusion [17•]. After excluding patients with a history of stroke/TIA and those with isolated/bilateral occlusions, the stroke risk fell to 3.8% in patients with 50–99% stenosis and 2.0% in those with 70–99% stenosis. The prevalence of ipsilateral stroke in patients with a unilateral, asymptomatic 50–99% stenosis was 2.0%, whereas the risk of any stroke was 2.9%. In this group of patients, the risk did not appear to increase with stenosis severity. Patients with bilateral, asymptomatic 50–99% stenosis or a 50–99% stenosis associated with a contralateral occlusion incurred a 6.5% stroke risk following cardiac surgery, whereas the risk of death/stroke was 9.1%. Patients with bilateral 80–99% stenosis undergoing a unilateral synchronous cardiac/carotid revascularization incurred a 5.7% risk of stroke in the hemisphere ipsilateral to the non-operated, contralateral stenosis [17•].

A history of stroke or TIA has been frequently identified as an independent predictor of perioperative stroke in patients undergoing cardiac surgery [1416]. A previous meta-analysis of patients with carotid stenosis undergoing CABG reported a risk of perioperative stroke of 8.5% in patients with previous TIA/stroke versus 2.2% in patients with no prior neurologic symptoms and identified prior stroke/TIA (odds ratio [OR], 3.6) and severe carotid stenosis/occlusion (OR, 4.3) as an independent predictor of stroke [4]. In the more recent meta-analysis, the outcomes of patients with symptomatic carotid stenosis were not separately reported. However, the high event rate in this patient population can be derived by the observation that after excluding symptomatic patients from the analysis, the stroke rate declined from 7.4% to 3.8% [17•].

Carotid Stenosis: The Wrong Culprit of Perioperative Stroke?

Patients undergoing CABG may have multiple sources of embolism. Although early embolism may result from manipulations of the heart and aorta, release of particulate matter from the cardiopulmonary-bypass pump, or air embolism, delayed embolism is often attributed to postoperative atrial fibrillation. Additional predisposing conditions may be the inflammation and prothrombotic states secondary to surgical trauma and associated tissue injury [18]. In the general population, the presence of severe atherosclerosis at the level of the aortic arch is considered one of the main risk factor for stroke beyond atrial fibrillation and carotid artery disease [19]. This may especially be the case at the time of cardiac surgery due to manipulations of the ascending aorta including cross-clamping, cannulation, and proximal graft anastomosis.

Although the association between carotid artery disease and perioperative stroke in patients undergoing CABG is undisputed, patients with carotid disease also may have severe atherosclerotic disease of the ascending aorta. As a consequence, the question arose whether focusing on the carotid stenosis was not looking for the wrong culprit instead of addressing the true—and difficult to treat—source of embolism, namely the ascending aorta [20]. Accordingly, a systematic review indicated that 50% of stroke sufferers did not have significant carotid disease and 60% of territorial infarctions on CT scan/autopsy could not be attributed to carotid disease alone [4]. However, little prospective data are available on the impact of atherosclerosis of the ascending aorta and the outcomes following CABG because most cardiac surgery databases do not track prospectively the extent of atherosclerotic disease in the ascending aorta [21]. A retrospective study on 862 patients who underwent CT scan of the aorta prior to cardiac surgery, although not reporting perioperative events, demonstrated an association between the extent of the aortic atheroma and long-term mortality [22]. Although preoperative CT scanning or transesophageal echocardiography is not recommended to detect aortic atherosclerosis, the new American CABG guidelines state that routine intraoperative epiaortic ultrasound scanning is reasonable to evaluate the presence, location, and severity of plaque in the ascending aorta to reduce the incidence of perioperative atheroembolic complications (Class IIa, LOE B) [10].

Carotid Revascularization for Stroke Prevention in Patients Undergoing Cardiac Surgery

Carotid Endarterectomy

In the United States, combined carotid endarterectomy (CEA)–CABG represented 1.1% of all CABG performed in the decade from 1993 to 2002 [23]. The Nationwide Inpatient Sample reported a stroke rate of 3.9%, a stroke or death rate of 8.6%, and a death rate of 5.4% among 26,197 patients undergoing combined CEA–CABG surgery [24]. A previous report on the same database showed that after correcting for differences in comorbidities the OR for postoperative stroke or death for CEA–CABG versus CABG alone was 1.38 (95% CI, 1.27–1.50) [23].

A recent tabular review of the literature reported among 11,854 patients undergoing simultaneous CEA-CABG an early death rate of 5% (3% cardiac and 1% neurologic), a stroke rate of 4%, a MI rate (available for 7027 patients) of 3%, a death or stroke rate of 8%, and a death, stroke, or MI rate of 10% [25•]. With respect to outcome data on CEA followed by CABG, the review could identify only 919 patients and reported an overall early death rate of 4%, a stroke rate of 2%, an MI rate of 6%, a death or stroke rate of 6%, and a death, stroke, or MI rate of 13%. Even more rare was CABG followed by CEA: among 335 patients, the authors reported an early death rate of 3%, a stroke rate of 5%, an MI rate of 1%, a death or stroke rate of 8%, and a death, stroke, or MI rate of 9% [25•].

In an analysis of combined coronary and carotid procedures performed in the United States between 2000 and 2004 collected in the Nationwide Inpatient Sample, over 95% of patients were asymptomatic from a carotid standpoint. However, among the 973 patients with symptomatic carotid stenosis, the postoperative stroke rate was as high as 14.2% [24]. Current recommendations for carotid revascularization in patients undergoing CABG are listed in Table 2.
Table 2

Guideline recommendations on the management of patients undergoing CABG

Guideline

Year

Recommendation

Grade/Class

American Carotida

2011

Carotid revascularization by CEA or CAS with embolic protection before or concurrent with myocardial revascularization surgery is reasonable in patients with greater than 80% carotid stenosis who have experienced ipsilateral retinal or hemispheric cerebral ischemic symptoms within 6 months

Class IIa, LOE C

In patients with asymptomatic carotid stenosis, even if severe, the safety and efficacy of carotid revascularization before or concurrent with myocardial revascularization are not well established

Class IIb, LOE C

American CABGb

2011

In the CABG patient with a previous TIA or stroke and a significant (50% to 99%) carotid artery stenosis, it is reasonable to consider carotid revascularization in conjunction with CABG. In such an individual, the sequence and timing (simultaneous or staged) of carotid intervention and CABG should be determined by the patient’s relative magnitudes of cerebral and myocardial dysfunction

Class IIa, LOE C

 

In the patient scheduled to undergo CABG who has no history of TIA or stroke, carotid revascularization may be considered in the presence of bilateral severe (70% to 99%) carotid stenoses or a unilateral severe carotid stenosis with a contralateral occlusion

Class IIb, LOE C

European Peripheralc

2011

Carotid revascularization is recommended in 70% to 99% symptomatic carotid stenosis

Class I, LOE C

Carotid revascularization may be considered in 50% to 69% symptomatic carotid stenosis, depending on patient-specific factors and clinical presentation

Class IIb, LOE C

Carotid revascularization may be considered in asymptomatic men with bilateral 70% to 99% carotid stenosis or 70% to 99% carotid stenosis and a contralateral occlusion

Class IIb, LOE C

Carotid revascularization may be considered in asymptomatic men with 70% to 99% carotid stenosis and ipsilateral previous silent cerebral infarction

Class IIb, LOE C

CABG coronary artery bypass grafting, CAS carotid artery stenting, CEA carotid endarterectomy, LOE level of evidence, TIA transient ischemic attack.

aData from ASA/ACCF/AHA/AANN/AANS/ACR/ASNR/CNS/SAIP/SCAI/SIR/SNIS/SVM/SVS guideline [36•]

bData from ACCF/AHA guideline [10].

cData from European Society of Cardiology guidelines [11•].

Carotid Artery Stenting

Carotid artery stenting (CAS) has recently come under fire because of inferior results in the randomized setting compared with CEA [26, 27]. However, several studies had flaws in the methodology, especially with respect to the minimal endovascular experience required to enroll patients [28]. A recent tabular review of the literature described among 905 patients undergoing simultaneous CAS followed by CABG an overall early death rate of 5%, a stroke rate of 3%, an MI rate of 2%, a death or stroke rate of 8%, and a death, stroke, or MI rate of 8% [25•]. Among the series, by far the largest experience (N = 356) came from a single center in the Netherlands with a rate of death, stroke, or MI from the time of CAS to 30 days after cardiac surgery of 6.8% [29]. The associated neurologic complication rates were low both at 30 days (major ipsilateral stroke 1.1%) and at a mean follow-up of 31 months (neurologic death 1.1% and major ipsilateral stroke 1.1%).

Although these outcomes compare well with the ones previously described for the surgical approach, it has to be underscored that the data for CAS followed by CABG remains limited. According to the Nationwide Inpatient Sample only 3.3% (N = 887) of all patients undergoing carotid revascularization and CABG between 2000 and 2004 (N = 27,084) in the United States had CAS prior to CABG, whereas the remaining were treated surgically [24]. Although the two groups may not be comparable, patients undergoing CAS followed by CABG had a significantly lower incidence of postoperative stroke (2.4% vs 3.9%) and stroke or death (6.9% vs 8.6%) than those managed with CEA and CABG. In multivariate analysis, the increased risk of stroke associated with the entirely surgical approach persisted (OR, 1.62; 95% CI, 1.1–2.5; P = 0.02) [24]. Still unresolved is the mandatory minimal duration of dual antiplatelet therapy following CAS prior to CABG [30]. Finally, synchronous CAS–CABG may be an alternative strategy to staged CEA–CABG for patients needing urgent coronary revascularization. A single-center experience on 90 patients undergoing same-day CAS and CABG reported a 30-day death, stroke rate, or MI rate of 2.2% [31]. Similarly, a prospective multicenter study on 101 patients undergoing the same hybrid procedure reported a death, MI, or stroke rate of 4% [32].

In our opinion, the main advantage of CAS prior to CABG compared with the combined surgical approach is the reduction of periprocedural MI. The CREST (Carotid Revascularization Endarterectomy Versus Stenting Trial) randomized 2502 patients to CEA or CAS and followed them up to 4 years. The periprocedural clinical MI rate was halved among CAS patients compared with CEA patients (hazard ratio [HR], 0.5; P = 0.032), whereas biomarker-only MIs were also numerically reduced (HR, 0.66; P = NS). Compared to patients without periprocedural cardiac biomarker elevation, mortality was significantly higher over 4 years for those with clinical MIs (HR, 3.4) and biomarker-only MIs (HR, 3.6) [33]. After adjusting for baseline risk factors, both clinical MIs (HR, 3.7) and biomarker-only MIs (HR, 2.9) remained independently associated with increased mortality. The presence of prior cardiovascular disease or CABG independently predicted both clinical MIs (HR, 2.2) and biomarker-only MIs (HR, 1.7). Additional independent predictors of both clinical and biomarker-only MIs included older age, diabetes mellitus, and renal insufficiency—all conditions frequently encountered among patients undergoing CABG. These findings parallel previous reports showing that even minor cardiac biomarker elevation independently predicted long-term mortality after vascular surgery [34, 35].

Ideally, the best management strategy for patients with severe asymptomatic carotid stenosis requiring open heart surgery should be investigated with a randomized clinical trial. Clinically relevant would be a noninferiority trial addressing three strategies: CEA plus CABG, CAS followed by CABG, and CABG only. It is unlikely that such a trial will ever be performed because to be adequately powered it would require thousands of patients and combined carotid and coronary revascularization represent only approximately 1% of all CABG procedures [23]. While the 2011 American carotid guidelines set CEA and CAS as comparable alternatives for carotid revascularization in patients undergoing CABG, the 2011 American CABG guidelines and the 2011 European ones indirectly affirm the same by simply giving recommendations for “carotid revascularization” without specifying the approach (Table 2) [11, 36•]. Of note, all of the guidelines were not able to incorporate the CREST-MI data [33].

Focusing on Perioperative Stroke: A Narrowed-Angle View?

In the debate on the utility of carotid revascularization in patients with carotid asymptomatic stenosis undergoing CABG the focus is commonly on perioperative stroke while little attention is given to long-term stroke prevention. Although the vast majority of those patients may undergo CABG without neurologic events, they still carry the long-term risk of stroke associated with carotid disease. This opens the debate on the role of revascularization in patients with asymptomatic carotid disease [37, 38]. The assumption that medical treatment alone may be sufficient to prevent ipsilateral strokes is hazardous, not supported by randomized data, and cannot be applied to patients with carotid disease undergoing CABG. Accordingly, the annual stroke risk of patients with carotid disease undergoing CABG is unknown because those patients have been excluded from carotid revascularization trials and natural history studies are lacking.

Real-life data REACH registry showed that patients with asymptomatic carotid disease (N = 3164) had nonfatal and fatal stroke rates of 2.7% and of 0.5% at 1 year, respectively [39]. In those patients, the stroke risk significantly and independently increased in the presence of peripheral arterial disease (OR, 1.8), hyperlipidemia (OR, 1.9), diabetes (OR, 2.1), and history of cerebrovascular disease (OR, 3.2), characteristics often encountered in patients undergoing CABG. A prospective natural history study showed that patients with asymptomatic carotid stenosis but evidence of (silent) embolic infarcts on CT scan had an annual stroke rate of 3.6% [40]. Exactly the same stroke rate was described in patients with asymptomatic carotid stenosis but embolic signals on transcranial Doppler [41]. Finally, in patients treated for symptomatic carotid disease, the stroke risk associated with the contralateral asymptomatic carotid artery was 3.7%/year in the presence of a stenosis greater than75% [42]. Opposing the uncertainty of the stroke risk in patients with untreated stenosis, long-term results of randomized trials have invariably shown that beyond 30 days both with CEA and CAS patients are exposed to an annual stroke rate that does not exceed 1% per year [4346].

Suggested Management Algorithm for Patients with Severe Carotid Disease Undergoing CABG

The management of patients with multilevel atherosclerotic disease should be tailored according to the clinical presentation. Accordingly, the event rates related to the symptomatic organ (eg, death or MI in acute coronary syndromes and stroke in symptomatic carotid stenosis) do peak in the acute phase of the corresponding disease. As previously mentioned, in the vast majority of patients with severe coronary and carotid disease the “leading organ” is the heart, whereas the carotid stenosis is asymptomatic [24]. The management of those patients should depend on the degree of CABG urgency as well as the severity of carotid disease (Fig. 1).
https://static-content.springer.com/image/art%3A10.1007%2Fs11886-012-0246-1/MediaObjects/11886_2012_246_Fig1_HTML.gif
Fig. 1

Management algorithm for patients with carotid stenosis undergoing coronary artery bypass grafting (CABG). CAD—coronary artery disease; CAS—carotid artery stenting; CEA—carotid endarterectomy

Patients with symptomatic stenosis ≥70% scheduled for CABG should undergo carotid revascularization, whereas in 50–69% carotid stenosis the indication for revascularization should be based on the estimated risks and benefits in the individual patient. As long as from the medical standpoint CABG can be delayed 4–5 weeks—because of the need for dual antiplatelet therapy—CAS followed by CABG should be considered a valuable if not preferable alternative to the combined surgical procedure due to the very high stroke rates in patients treated entirely surgically [24, 25•, 47]. In patients with associated unstable CAD, the combined CEA–CABG is the therapy of choice, whereas in centers with expertise the hybrid approach (ie, CAS followed by same-day CABG) may be considered.

In asymptomatic carotid artery disease, it is reasonable to treat a carotid stenosis ≥80%—not primarily for perioperative stroke reduction but more for long-term stroke prevention—as long as the estimated death/stroke rate is ≤3%. If CABG is not urgent and the expertise is available, CAS followed by CABG should be considered as an alternative to the combined CEA–CABG because of the lower MI rate. If the estimated death/stroke risk associated to the carotid procedure exceeds 3%, then the carotid stenosis should not be treated. The life expectancy threshold of 5 years commonly advocated to treat an asymptomatic carotid stenosis should per definition be met by all patients undergoing CABG or they would not qualify for cardiac surgery.

As previously described, patients with bilateral severe carotid stenosis undergoing CABG have a high risk of perioperative stroke even in the absence of carotid symptoms [17]. Carotid revascularization prior to CABG is appropriate and CAS should be favored if the expertise is available. Accordingly, the presence of a severe contralateral carotid artery stenosis or occlusion increases the risk of stroke associated with CEA but not with CAS [48, 49]. Patients with this with bilateral severe carotid stenosis and unstable CAD requiring CABG are at very high risk of death or stroke and the hybrid procedure (ie, unilateral CAS followed by CABG) should be considered the therapy of choice.

Alternative Strategies to Reduce Stroke Risk in Patients Requiring Coronary Revascularization

Off-Pump CABG

Despite several encouraging single-center reports on off-pump CABG, a meta-analysis of small-scale studies randomizing patients (N = 2018) to off-pump or on-pump surgery did not detect a benefit in terms of major cardiovascular events or stroke from off-pump CABG [50]. A subsequent randomized trial of 2203 patients allocated to the two strategies did not demonstrate advantages from off-pump versus on-pump surgery in 30-day stroke (1.3% vs 0.7%) or major cardiovascular events (7.0% vs 5.6%) [51]. Despite a lack of superiority over on-pump CABG, subgroups of patients may benefit from the lack of circulatory arrest and clamping of the aorta, namely patients with carotid stenosis and those with severe atheromatous disease of the ascending aorta.

With respect to patients with carotid disease, a recent review collected 345 patients undergoing combined off-pump CABG and CEA and reported a very encouraging early death rate of 2%; a stroke rate of 0%; an MI rate of 1%; a death or stroke rate of 2%; and a death, stroke, or MI rate of 3% [25•]. In a case-control study, 211 patients with severe atheromatous disease of the ascending aorta or the aortic arch undergoing off-pump CABG were matched with 211 patients with the same degree of aortic disease who underwent on-pump CABG [52]. In-hospital mortality was 11.4% for on-pump and 3.8% for off-pump CABG (P = 0.003), and on-pump CABG was identified as independent predictor of mortality. However, the difference in stroke (4.7% vs 2.4%; P = 0.08) did not reach statistical significance [52].

Percutaneous Coronary Intervention

In a prospective registry involving four high-volume Italian centers, 239 consecutive patients with advanced carotid and coronary disease were treated with staged or simultaneous CAS and percutaneous coronary intervention (PCI). The incidence of death, MI, or stroke occurring between the first revascularization procedure and 30 days after treatment of the second vascular territory affected was 4.2%, whereas the stroke rate was 2.5% [53]. The patients treated were likely at lower risk than the usual CEA–CABG population: as an example the proportion of one-, two-, and three-vessel CAD was 58%, 25%, and 17%, respectively. Nevertheless, also in patients with advanced CAD randomized studies have shown that CABG and PCI with drug-eluting stents conveyed similar results in terms of death, MI, or stroke. Although patients undergoing PCI had more repeat revascularization procedures, they suffered less strokes than those undergoing CABG [54, 55].

Conclusions

Patients with severe carotid and coronary disease—especially if they require CABG—are at high risk of cardiac events and stroke. Although stroke at the time of cardiac surgery is a devastating event associated with increased mortality, morbidity, and health care costs, the evidence supporting a specific strategy to reduce stroke in patients with carotid disease remains elusive. While carotid disease accounts only for a proportion of perioperative strokes, carotid revascularization should be considered for patients with symptomatic carotid disease and bilateral severe carotid stenosis. In patients with asymptomatic severe carotid stenosis, risks and benefits of carotid revascularization should be addressed case by case and the decision to proceed should be based more on the long-term stroke prevention than on perioperative stroke reduction. With respect to the carotid revascularization strategies in patients undergoing CABG, CAS should be favored—if the expertise is available and CABG is not urgent—because of the lower incidence of periprocedural MI, an event clearly associated with long-term mortality. Although the optimal antiplatelet regimen and the delay between procedures in patients undergoing CAS followed by CABG needs to be defined, preliminary data on the hybrid approach (ie, CAS followed by same-day CABG) appear promising. Other strategies to reduce periprocedural stroke include off-pump CABG and percutaneous instead of surgical coronary revascularization. Irrespective of the revascularization strategy, a broad disease management approach based on lifestyle modification and pharmacologic cardiovascular prevention is more likely to affect both the quality and duration of life of patients with severe coronary and carotid disease than carotid revascularization itself.

Disclosure

Conflicts of interest: M. Roffi: none; F. Ribichini: none; F. Castriota: has received grant support from Medtronic and Boston Scientific; has received a consulting fee or honorarium from Medtronic and Boston Scientific; and has received travel/accommodations expenses covered or reimbursed from Medtronic and Boston Scientific; A. Cremonesi: has received grant support from Medtronic and Boston Scientific; has received a consulting fee or honorarium from Medtronic and Boston Scientific; and has received travel/accommodations expenses covered or reimbursed from Medtronic and Boston Scientific.

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© Springer Science+Business Media, LLC 2012