Carotid endarterectomy for carotid stenosis in patients selected for coronary artery bypass graft surgery

Abstract

Background

Carotid stenosis and coronary artery disease can occur simultaneously. In patients with coronary artery disease who are scheduled for coronary artery bypass graft (CABG) surgery, but who also have carotid artery stenosis, there is controversy about the role of carotid surgery. It is not known whether any benefit from prophylactic carotid endarterectomy (by avoiding stroke and neurological dysfunction complicating CABG surgery) outweighs the risks.

Objectives

To assess, in patients undergoing CABG surgery with a carotid stenosis more than 50%, the effects of carotid endarterectomy plus best medical therapy compared with best medical therapy alone on the overall risk of major clinical outcomes including death, stroke, and myocardial infarction.

Search methods

We searched the trials registers of the Cochrane Stroke Group (searched October 2008) and the Cochrane Heart Group (searched November 2008). In addition, we searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 4, 2008), MEDLINE (1966 to November 2008), EMBASE (1980 to November 2008), reference lists of identified trials, and ongoing trials and research registers (last searched November 2008).

Selection criteria

We planned to include all truly randomised controlled trials comparing carotid endarterectomy plus best medical therapy with best medical therapy alone in patients selected for CABG surgery. The main outcome was perioperative death.

Data collection and analysis

We planned for two review authors to independently assess the methodological quality of included studies, and extract data.

Main results

We did not find any eligible studies.

Authors' conclusions

We found no evidence from randomised trials by which to assess the benefits and risks of prophylactic carotid surgery before CABG surgery. Randomised controlled trials are required to reliably document the risks and benefits of such procedures.

Plain language summary

Carotid endarterectomy for carotid stenosis in patients selected for coronary artery bypass graft surgery

People who have coronary artery disease requiring coronary artery bypass graft (CABG) surgery often have narrowing of other arteries. If the carotid artery, the artery carrying blood to the brain, is narrow (called carotid stenosis), this may increase the risk of stroke and other brain damage, complicating CABG surgery. Surgery to remove the carotid narrowing might prevent these complications of CABG surgery, but also has risks. We found no reliable evidence from randomised trials to indicate whether or not to perform preventive carotid surgery in patients who are going to have CABG surgery.

Background

Atherosclerosis is a generalised disease that has an effect on all the vessels to varying degrees. The major diseases are carotid stenosis and coronary artery disease, which can occur simultaneously (Mackey 1990; Ouriel 2001).

Different studies have reported various incidences for concomitant cerebrovascular disease and coronary atherosclerosis. The prevalence of carotid stenosis (greater than 50%) in patients with coronary artery disease has been reported to be as high as 22% (Schwartz 1995). The prevalence of severe carotid stenosis (greater than 75%) in similar patients varied from 1% to 12% in the literature (Evagelopoulos 2000; Hines 1998; Ricotta 1995; Schwartz 1995). In a recently published study the prevalence of carotid stenosis in Japanese patients with multivessel coronary artery disease was 29.8% (Tanimoto 2005).

Stroke and myocardial infarction are major complications following coronary artery bypass graft (CABG) surgery, which can result in significant morbidity and mortality. In addition, both have been a critical complication following carotid endarterectomy (Huh 2003).

The risk of stroke is estimated to be 1% to 2% in patients selected for CABG surgery (Blacker 2004; Naylor 2002) and 2.5% and 5% in patients undergoing carotid endarterectomy with asymptomatic and symptomatic carotid stenosis respectively (ACAS 1995; NASCET 2001). Patients with a unilateral stenosis greater than 50% had a 3% risk of stroke after CABG surgery, rising to 5% for patients with bilateral stenosis greater than 50%, and 11% for those CABG patients with occlusion (Naylor 2002).

ACAS reported that 49% of perioperative deaths in patients undergoing carotid endarterectomy were due to cardiac causes, of which myocardial infarction was the main cause (ACAS 1995).

Perioperative complication rates for the combined procedure of simultaneous CABG surgery and carotid endarterectomy are unacceptably high, and have been reported as a 1.5% to 8.1% risk of death, and a risk of stroke of up to 6.3% (Dylewski 2001; Gaudino 2001; Halpin 1994; Hertzer 1989; Perler 1985; Ricotta 2003; Rizzo 1992; Saha 2000). One meta‐analysis reported the relative risk of stroke and death for patients undergoing the combined procedure as 1.50 and 1.55 respectively (Borger 1999). This high risk of neurological dysfunction after CABG surgery has led to much debate about the role of carotid surgery in such patients (Dylewski 2001; Huh 2003).

Symptomatic carotid stenosis

A Cochrane Review has assessed the efficacy of carotid endarterectomy in adults with symptomatic carotid stenosis. It showed carotid endarterectomy reduces the risk of disabling stroke or death in patients with severe carotid stenosis, but only for surgically fit patients in hospitals with complication rates of less than 6%. The review authors found that, in patients with lesser degrees of stenosis, surgery increased the risk of complications by 20% (Cina 1999).

Another review assessed other characteristics that might have an effect on outcome. The authors analysed pooled data from the European Carotid Surgery Trial (ECST 1998) and the North American Symptomatic Carotid Endarterectomy Trial (NASCET 2001). They found three significant and clinically important subgroups and concluded that, in men and in the elderly, surgery could be beneficial. There was also a trend towards increased benefit in patients with a previous myocardial infarction (Rothwell 2004).

Asymptomatic carotid stenosis

The management of asymptomatic carotid lesion is much more controversial. In order to determine the effects of carotid endarterectomy for patients with asymptomatic carotid stenosis, three trials with a total of 5223 patients were included in a Cochrane Review. Carotid endarterectomy reduced the overall risk of ipsilateral stroke and any stroke, although the overall net excess of operation‐related perioperative stroke or death was 2.9%. Compared with trials of endarterectomy for symptomatic stenosis, lower operation‐related stroke or death has been reported (ECST 1998 7%; NASCET 2001 5.4%). It is consistent with the view that operative risk is less for asymptomatic carotid stenosis. This review did not find any statistically significant difference in treatment effect estimates among patients with different grades of stenosis (Chambers 2005).

The Asymptomatic Carotid Stenosis Trial (ACST 2004) suggested that immediate carotid endarterectomy halved the net five‐year stroke risk from about 12% to about 6% (including 3% perioperative hazard). However, inappropriate selection of patients or poor surgery could obviate such benefits.

The Asymptomatic Carotid Atherosclerosis Study concluded that patients with asymptomatic carotid artery stenosis of 60% or more, who are good candidates for elective surgery, will have a reduced five‐year risk of ipsilateral stroke if carotid endarterectomy is performed with less than 3% perioperative morbidity and mortality (ACAS 1995). Despite these data, a Cochrane Review reported that the absolute risk reduction is small: approximately 1% in each year over the first few years of follow up (Chambers 2005). The review authors concluded that, for most asymptomatic patients, a surgical operation to remove the stenosis has little benefit. They could not identify a threshold level of stenosis for selecting asymptomatic patients for surgery. Moreover, the applicability of surgical management for asymptomatic carotid stenosis to patients with concomitant carotid and coronary disease also remains controversial.

Objectives

To assess the effects of carotid endarterectomy plus best medical therapy compared with best medical therapy alone on the major clinical outcomes, including death, stroke, and myocardial infarction, in patients undergoing CABG surgery with carotid stenosis greater than 50%.

Methods

Criteria for considering studies for this review

Types of studies

We planned to include all truly randomised controlled trials comparing carotid endarterectomy plus best medical therapy with best medical therapy alone in patients selected for CABG surgery. We would only include studies if data for clinically significant endpoints, such as ischaemic stroke, haemorrhagic stroke, or death, were available.

Types of participants

We planned to include patients selected for CABG surgery who had a carotid stenosis of more than 50% (either symptomatic or asymptomatic carotid stenosis) measured by Doppler sonography or angiography, according to NASCET 2001 or ECST 1998 methods. We planned to exclude patients with comorbid disorders, or those who had not had adequate assessment.

Types of interventions

We planned to compare carotid endarterectomy plus best medical therapy with best medical therapy alone. We would include carotid endarterectomy by any technique, conventional or eversion, and by any type of anaesthesia, local or general. We would exclude simultaneous carotid endarterectomy plus major vascular surgery versus major vascular surgery alone.

Types of outcome measures

The main outcome was perioperative death.

Secondary outcomes were as follows:

• perioperative stroke, either ischaemic or haemorrhagic;

• perioperative myocardial infarction (confirmed by electrocardiography (ECG) and enzymes);

• perioperative stroke or death or myocardial infarction;

• stroke during follow up;

• death during follow up;

• myocardial infarction during follow up.

We defined a perioperative outcome as an endpoint occurring within 30 days of randomisation. This included events that happened after randomisation but before carotid endarterectomy in the intervention group and also included events in the control group.

Search methods for identification of studies

See the 'Specialized register' section in the Cochrane Stroke Group module.

We searched the trials registers of the Cochrane Stroke Group (which was last searched by the Managing Editor in October 2008) and the Cochrane Heart Group (searched November 2008). In addition, we searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 4, 2008), MEDLINE (1966 to November 2008) (Appendix 1) and EMBASE (1980 to November 2008) (Appendix 2).

In an effort to identify further published, unpublished and ongoing trials, we searched reference lists of identified trials and the ongoing trials registers Current Controlled Trials (http://www.controlled‐trials.com/) and the Internet Stroke Center Stroke Trials Registry (http://www.strokecenter.org/) (last searched November 2008).

Data collection and analysis

Two review authors (BMD and SMH) independently reviewed the titles and abstracts of identified studies for possible inclusion in the review. If a title or abstract appeared to be relevant, the review authors independently assessed the full text of the article. We resolved disagreements between review authors by discussion. We contacted study authors if further clarification was necessary.

Quality assessment

We planned for two review authors to independently assess the methodological quality of included studies by considering the following:

• randomisation (true or quasi randomisation);

• allocation concealment: adequate, inadequate, unclear;

• intention‐to‐treat analysis;

• completeness of follow up.

We resolved disagreements between review authors by discussion.

Data extraction

We planned for two review authors to independently extract the following data from eligible studies, and record the information on standard data extraction forms.

• Participants: sample size, age, sex, number of patients originally allocated to each treatment group, diagnostic criteria used for carotid stenosis, diagnostic criteria used for myocardial infarction, numbers of patients in each group with symptomatic or asymptomatic carotid stenosis.

• Intervention: time interval from onset to randomisation and randomisation to surgery, type of anaesthesia, technique of carotid endarterectomy, any other major vascular surgery.

• Outcomes: number of patients in each group with outcome events, including stroke, myocardial infarction and death.

• Withdrawals and adverse effects.

• Length of follow up.

• Any additional important information.

We would resolve any disagreements between review authors by discussion.

Data analysis

We used the Cochrane Review Manager software, RevMan 5.0 (RevMan 2008).

We decided to use intention‐to‐treat analysis and relative risk to analyse outcomes. We planned to estimate the pooled effect size by using a random‐effects model. It would be implemented only if the studies provided sufficient data, the studies or subgroups of studies were considered clinically homogeneous, and if statistical heterogeneity was not demonstrated.

We planned to assess homogeneity with the I² statistic. If data were statistically heterogeneous, we aimed to identify the potential sources and discuss the possible reasons.

If several studies were identified, we planned to perform subgroup analyses according to: participants' age; participants' sex; degree of stenosis; and high‐quality versus low‐quality studies.

We also planned a subgroup analysis for patients with symptomatic and asymptomatic carotid stenosis to determine if there were any differences in outcomes.

Results

Description of studies

We found 980 titles by searching the literature. There was considerable duplication among different databases. After excluding irrelevant studies and duplicates, we finally reviewed 70 abstracts, of which none met the inclusion criteria of our review. Therefore, there were no full articles on which we could conduct quality assessment, data extraction or data analysis. We found no completed or ongoing randomised controlled trials.

Risk of bias in included studies

We found no eligible studies for inclusion.

Effects of interventions

We found no eligible studies for inclusion.

Discussion

Every year, thousands of people undergo CABG surgery all over the world. In many centres, but not all, it has become routine practice to perform carotid evaluation before this major surgery in order to assess the patency of carotid arteries. Some candidates for CABG surgery have significant symptomatic or asymptomatic carotid stenosis. In a non‐emergency situation, the most important question for the surgeons is whether they should correct carotid stenosis; if so, should they do this before or after CABG surgery, or should they consider performing both procedures at the same time? The presence of carotid artery stenosis is a significant predictor of poor outcome in patients undergoing CABG surgery (Brener 1987). Although carotid stenosis is found in about 8% of candidates for CABG surgery, optimal management is still controversial. We aimed to review all truly randomised controlled trials comparing endarterectomy and best medical therapy in patients scheduled for CABG surgery. Unfortunately, we could not find any studies that fitted our inclusion criteria. We believe that, since carotid stenosis worsens prognosis in CABG surgery, many surgeons aim to correct the stenosis before CABG surgery without reliable evidence that this will improve the prognosis.  A systematic review of outcomes in patients with staged carotid stenting and CABG surgery (Guzman 2008) demonstrated that the combined incidence of death and stroke in such patients remains high. They concluded that carotid stenosis is a marker of risk that might persist independently of its treatment. This may also be true for staged endarterectomy and CABG surgery. Another systematic review of outcomes following synchronous endarterectomy and CABG surgery demonstrated that these procedures are associated with an important cardiovascular risk (Naylor 2003).

Authors' conclusions

Implications for practice.

Although carotid stenosis is a predictor of poor outcome in CABG surgery, we found no reliable evidence to assess the balance of risk and benefit of endarterectomy before CABG surgery, and whether it results in a better overall prognosis.

Implications for research.

Future studies should be planned to document the risks and benefits of endarterectomy before CABG surgery; a trial is warranted.

History

Protocol first published: Issue 3, 2006
 Review first published: Issue 4, 2009

Date	Event	Description
7 July 2008	Amended	Converted to new review format.

Appendices

Appendix 1. MEDLINE search strategy

The following search strategy was used for MEDLINE and modified for CENTRAL.

1. Endarterectomy, Carotid/ 
 2. (carotid adj5 (endarterectomy or surgery)).tw. 
 3. cea.tw. 
 4. 1 or 2 or 3 
 5. carotid artery diseases/ or carotid artery thrombosis/ or carotid stenosis/ 
 6. exp Carotid Arteries/ 
 7. (carotid adj5 (stenosis or thrombo$ or disease$ or arter$ or narrow$ or plaque$)).tw. 
 8. 5 or 6 or 7 
 9. Endarterectomy/ 
 10. Vascular Surgical Procedures/ 
 11. 9 or 10 
 12. 8 and 11 
 13. carotid artery diseases/su or carotid artery thrombosis/su or carotid stenosis/su 
 14. exp Carotid Arteries/su 
 15. 4 or 12 or 13 or 14 
 16. exp Coronary Artery Bypass/ 
 17. ((coronary or aortocoronary) adj5 (bypass or shunt or anastomosis or graft or surgery)).tw. 
 18. CABG.tw. 
 19. 16 or 17 or 18 
 20. coronary disease/ or coronary arteriosclerosis/ or exp coronary stenosis/ or coronary thrombosis/ 
 21. Coronary Vessels/ 
 22. (coronary adj (arterioscler$ or stenosis or thrombo$ or disease$ or arter$)).tw. 
 23. 20 or 21 or 22 
 24. Cardiac Surgical Procedures/ 
 25. 23 and 24 
 26. coronary disease/su or coronary arteriosclerosis/su or exp coronary stenosis/su or coronary thrombosis/su 
 27. Coronary Vessels/su 
 28. 26 or 27 
 29. 19 or 25 or 28 
 30. 15 and 29

Appendix 2. EMBASE search strategy

1. carotid artery surgery/ or carotid endarterectomy/ 
 2. (carotid adj5 (endarterectomy or surgery)).tw. 
 3. cea.tw. 
 4. 1 or 2 or 3 
 5. carotid artery disease/ or carotid artery obstruction/ or carotid artery thrombosis/ or internal carotid artery occlusion/ 
 6. exp carotid artery/ 
 7. (carotid adj5 (stenosis or thrombo$ or disease$ or arter$ or narrow$ or plaque$)).tw. 
 8. 5 or 6 or 7 
 9. Endarterectomy/ 
 10. vascular surgery/ 
 11. 9 or 10 
 12. 8 and 11 
 13. carotid artery disease/su or carotid artery obstruction/su or carotid artery thrombosis/su or internal carotid artery occlusion/su 
 14. exp carotid artery/su 
 15. 4 or 12 or 13 or 14 
 16. coronary artery bypass graft/ or coronary artery bypass surgery/ 
 17. ((coronary or aortocoronary) adj5 (bypass or shunt or anastomosis or graft or surgery)).tw. 
 18. CABG.tw. 
 19. 16 or 17 or 18 
 20. coronary artery disease/ or coronary artery atherosclerosis/ or coronary artery obstruction/ or coronary artery thrombosis/ 
 21. Coronary Blood Vessel/ 
 22. (coronary adj (arterioscler$ or stenosis or thrombo$ or disease$ or arter$)).tw. 
 23. 20 or 21 or 22 
 24. coronary artery surgery/ 
 25. 23 and 24 
 26. coronary artery disease/su or coronary artery atherosclerosis/su or coronary artery obstruction/su or coronary artery thrombosis/su 
 27. Coronary Blood Vessel/su 
 28. 26 or 27 
 29. 19 or 25 or 28 
 30. 15 and 29

Contributions of authors

Sara Mortaz Hejri: contact author, search strategy section, review of literature. 
 Babak Mostafazadeh Davani: review of literature for the Background section and inclusion criteria, review of abstracts and titles. 
 Mohamed Ali Sahraian: Assistant Professor, determining objectives and outcomes, and contributing to the Discussion section.

Sources of support

Internal sources

• Student Scientific Research Center, Tehran University of Medical Sciences, Iran.

External sources

• No sources of support supplied

Declarations of interest

We have no conflict of interest to declare.

New