In patients undergoing cardiac surgery does asymptomatic significant carotid artery stenosis warrant carotid endarterectomy
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a Manchester Royal Infirmary, Oxford Road, Manchester, M13 9WL, UK
b Department of Cardiothoracic Surgery, James Cook University Hospital, Middlesbrough, UK
Abstract
A best evidence topic in cardiovascular surgery was written according to a structured protocol. The question addressed was whether asymptomatic significant carotid artery stenosis (ASCAS) warrants carotid endarterectomy (CEA) in patients undergoing cardiac surgery. 128 Papers were found using the reported search, of these 10 presented represent the best evidence to answer the clinical question. The author, journal, date and country of publication, patient group studied, study type, relevant outcomes, results, and study weaknesses of these papers are tabulated. We conclude that low risk, younger patients with a significant asymptomatic carotid artery stenosis should be considered for carotid endarterectomy at some stage. There is, however, no strong evidence that this must be performed prior to, or during CABG.
Key Words: Evidence-based medicine; Thoracic surgery; Carotid endarterectomy
1. Introduction
A best evidence topic was constructed according to a structured protocol. This protocol is fully described in the ICVTS [1].
2. Clinical scenario
You see a patient on the coronary care unit referred for urgent CABG following angiographically demonstrated triple vessel disease including a significant left main stem lesion. On examination he is found to have a right sided carotid bruit. He is asymptomatic, having had no cerebrovascular accidents (CVAs) or transient ischaemic accidents (TIAs) in the past. He is on an anti-platelet agent.
On carotid Doppler examination he is found to have a 70% stenosis of the internal carotid artery on the right side. You wonder whether he would benefit from synchronous or staged CEA at the same time as CABG but you decide to search for the evidence for this prior to consulting a vascular surgeon.
3. Three part question
In [patients undergoing cardiac surgery] does [asymptomatic significant carotid artery stenosis] reduce the long term incidence of [stroke].
4. Search strategy
Medline 1966-Feb 2005 using OVID interface [exp thoracic surgery/OR cardiac surgery.mp OR exp cardiac surgical procedures/OR exp coronary artery bypass/OR CABG.mp] AND [exp carotid stenosis/OR carotid stenosis.mp /OR carotid artery stenosis.mp] AND [exp endarterectomy, carotid/OR carotid endarterectomy.mp OR CEA.mp] LIMIT to human studies. In addition, the AHA guidelines and NICE guidelines were hand searched.
5. Search outcome
Two hundred and ten papers were found of which 10 were deemed to be relevant. These papers are presented in Table 1.
6. Results
There are several sources of papers that must be considered when addressing this difficult issue. Firstly, there are cohort studies looking at the results of various combinations of Carotid endarterectomy (CEA) and CABG or Coronary arterial bypass grafting without CEA. There are also several meta-analyses summarising these papers. Secondly, there are very strong multicentre trials that look at the issue of whether lone asymptomatic carotid stenosis without coronary disease mandates carotid endarterectomy. And thirdly, there are a number of guidelines that attempt to put these studies together to form a protocol for the treatment of Carotid stenosis in patients undergoing CABG.
Of the meta-analyses of cohort studies that investigate CABG and CEA, Das et al. [8] summarised the published incidences of stroke and death for each strategy performed. CEA followed by CABG has a stroke rate of 1.5%, unprotected CABG then CEA had a stroke rate of 3.8%, CABG and CEA at the same operation had a stroke rate of 3.9%. Their findings that prior CEA then CABG is superior to alternative strategies was supported by the meta-analysis by Borger et al. [9] who summarised 16 studies and concluded that CEA followed by CABG has a stroke rate of 3.2% compared to a combined approach that had a stroke rate of 6% (P=0.068). Naylor et al. [2] provided a further update on this issue in 2003 and again concluded that CEA prior to CABG was the safest treatment. These meta-analyses also provided breakdowns for asymptomatic patients and the findings were similar. A further weakness is that these meta-analyses did not report any cohorts of patients who had a significant stenosis but had a CABG alone (other than prior to delayed CEA). Gaudino et al. in 2001 reported 5 year follow up of a small cohort of 139 asymptomatic patients undergoing CABG alone compared to CEA and CABG. There was only one perioperative stroke in each group, but by 5 years 17 patients (24%) who did not have CEA had a stroke, compared to only one patient in the treatment group. We found no further studies such as this, however, with medium term follow up after these two strategies.
The studies into lone asymptomatic carotid stenosis are, however, impressive. In 2004 the Asymptomatic Carotid Surgery Trial (ACST) [7] reported their medium term results from 3120 patients randomised from 126 centres in 30 countries. They found that Carotid endarterectomy in asymptomatic stenosis led to a 5-year stroke rate of 6.4% compared to a stroke rate of 11.8% in patients randomised to the control group (P<0.0001).
This study supported the findings of the Asymptomatic Carotid Atherosclerosis Study [5] in 1995, that showed in a study of 1662 patients that those who had an endarterectomy had a 5-year incidence of stroke of 5% compared to 11% in the control group. These two RCTs contradicted a previous large cohort study by the European Carotid Surgery trialists collaborative who performed a sub-analysis of their RCT and found that those with an untreated carotid stenosis had only a 5.7% risk of stroke at 3 years and concluded that the benefit of surgical intervention would probably be contra-indicated. Finally, a Cochrane review in 2004 [6] combined these two RCTs with 4 further RCTs to show a small benefit in favour of Carotid endarterectomy for asymptomatic stenosis.
The third area of evidence is that of guidelines. The American Heart Association has provided two relevant guidelines in this area in 1998 and 2004 [10, 11]. In 1998 the AHA provided guidelines for carotid endarterectomy. They concluded that in patients with an operative mortality of <3% and an expected life expectancy of more than 5 years requiring CABG with an asymptomatic carotid stenosis of more than 60%, carotid endarterectomy was not a proven indication but was an acceptable indication (based on grade C evidence). Patients with higher mortality may also have an acceptable indication if bilateral stenoses were present. This was also supported in the 2004 guidelines on coronary bypass grafting, where the AHA concluded that endarterectomy is ‘probably’ indicated in asymptomatic stenoses over 80% (based on grade C evidence).
Therefore based on the above evidence, it is clear that lower risk patients with a significant asymptomatic carotid stenosis should be considered for carotid entarterectomy at some stage. When coronary arterial surgery is also required it is far less clear as to when the endarterectomy should be performed, and there is no strong evidence that this should be performed prior to, or during the coronary arterial bypass procedure.
7. Clinical bottom line
Low risk, younger patients with a significant asymptomatic carotid artery stenosis should be considered for carotid endarterectomy at some stage. There is, however, no strong evidence that this must be performed prior to, or during CABG.
References
Dunning J, Prendergast B, Mackway-Jones K. Towards evidence based medicine in cardiothoracic surgery: best BETS. Interact CardioVasc Thorac Surg 2003;2:405–409.
Naylor R, Cuffe RL, Rothwell PM, Loftus IM, Bell PR. A systematic review of outcome following synchronous carotid endarterectomy and coronary artery bypass: influence of surgical and patient variables. Eur J Vasc Endovasc Surg 2003;26:230–241.
Gaudino M, Glieca F, Luciani N, Cellini C, Morelli M, Spatuzza P, Di Mauro M, Alessandrini F, Possati G. Should severe monolateral asymptomatic carotid artery stenosis be treated at the time of coronary artery bypass operation Eur J Cardiothorac Surg 2001;19:619–626.
Randomised trial of endarterectomy for recently symptomatic carotid stenosis: final results of the MRC European Carotid Surgery Trial (ECST). Lancet 1998;351:1379–1387.
. Executive Committee for the Asymptomatic Carotid Atherosclerosis Study. Endarterectomy for asymptomatic carotid artery stenosis. J Am Med Assoc 1995;273:1421–1428.
Chambers BR, You RX, Donnan GA. Carotid endarterectomy for asymptomatic carotid stenosis (Cochrane Review). The Cochrane Library 2004;Chichester, UK: John Wiley & Sons, Ltd In:.
. The European Carotid Surgery Trialists Collaborative Group. Risk of stroke in the distribution of an asymptomatic carotid artery. Lancet 1995;345:209–212.
Das SK, Brow TD, Pepper J. Continuing controversy in the management of concomitant coronary and carotid disease: an overview. Int J Cardiol 2000;74:47–65.
Borger MA, Fremes SE, Weisel RD, Cohen G, Rao V, Lindsay TF, Naylor CD. Coronary Bypass and Carotid Endarterectomy: Does a Combined Approach Increase Risk A Metaanalysis. Ann Thorac Surg 1999;68:14–21.
Biller J, Feinberg WM, Castaldo JE, Whittemore AD, Harbaugh RE, Dempsey RJ, Caplan LR, Kresowik TF, Matchar DB, Toole JF, Easton JD, Adams HP. Guidelines for carotid endarterectomy: a statement for healthcare professionals from a special writing group of the stroke Council. American Heart Association Circulation Feb 1998;97:501–509.(Michael O. Murphy, Jonath)
b Department of Cardiothoracic Surgery, James Cook University Hospital, Middlesbrough, UK
Abstract
A best evidence topic in cardiovascular surgery was written according to a structured protocol. The question addressed was whether asymptomatic significant carotid artery stenosis (ASCAS) warrants carotid endarterectomy (CEA) in patients undergoing cardiac surgery. 128 Papers were found using the reported search, of these 10 presented represent the best evidence to answer the clinical question. The author, journal, date and country of publication, patient group studied, study type, relevant outcomes, results, and study weaknesses of these papers are tabulated. We conclude that low risk, younger patients with a significant asymptomatic carotid artery stenosis should be considered for carotid endarterectomy at some stage. There is, however, no strong evidence that this must be performed prior to, or during CABG.
Key Words: Evidence-based medicine; Thoracic surgery; Carotid endarterectomy
1. Introduction
A best evidence topic was constructed according to a structured protocol. This protocol is fully described in the ICVTS [1].
2. Clinical scenario
You see a patient on the coronary care unit referred for urgent CABG following angiographically demonstrated triple vessel disease including a significant left main stem lesion. On examination he is found to have a right sided carotid bruit. He is asymptomatic, having had no cerebrovascular accidents (CVAs) or transient ischaemic accidents (TIAs) in the past. He is on an anti-platelet agent.
On carotid Doppler examination he is found to have a 70% stenosis of the internal carotid artery on the right side. You wonder whether he would benefit from synchronous or staged CEA at the same time as CABG but you decide to search for the evidence for this prior to consulting a vascular surgeon.
3. Three part question
In [patients undergoing cardiac surgery] does [asymptomatic significant carotid artery stenosis] reduce the long term incidence of [stroke].
4. Search strategy
Medline 1966-Feb 2005 using OVID interface [exp thoracic surgery/OR cardiac surgery.mp OR exp cardiac surgical procedures/OR exp coronary artery bypass/OR CABG.mp] AND [exp carotid stenosis/OR carotid stenosis.mp /OR carotid artery stenosis.mp] AND [exp endarterectomy, carotid/OR carotid endarterectomy.mp OR CEA.mp] LIMIT to human studies. In addition, the AHA guidelines and NICE guidelines were hand searched.
5. Search outcome
Two hundred and ten papers were found of which 10 were deemed to be relevant. These papers are presented in Table 1.
6. Results
There are several sources of papers that must be considered when addressing this difficult issue. Firstly, there are cohort studies looking at the results of various combinations of Carotid endarterectomy (CEA) and CABG or Coronary arterial bypass grafting without CEA. There are also several meta-analyses summarising these papers. Secondly, there are very strong multicentre trials that look at the issue of whether lone asymptomatic carotid stenosis without coronary disease mandates carotid endarterectomy. And thirdly, there are a number of guidelines that attempt to put these studies together to form a protocol for the treatment of Carotid stenosis in patients undergoing CABG.
Of the meta-analyses of cohort studies that investigate CABG and CEA, Das et al. [8] summarised the published incidences of stroke and death for each strategy performed. CEA followed by CABG has a stroke rate of 1.5%, unprotected CABG then CEA had a stroke rate of 3.8%, CABG and CEA at the same operation had a stroke rate of 3.9%. Their findings that prior CEA then CABG is superior to alternative strategies was supported by the meta-analysis by Borger et al. [9] who summarised 16 studies and concluded that CEA followed by CABG has a stroke rate of 3.2% compared to a combined approach that had a stroke rate of 6% (P=0.068). Naylor et al. [2] provided a further update on this issue in 2003 and again concluded that CEA prior to CABG was the safest treatment. These meta-analyses also provided breakdowns for asymptomatic patients and the findings were similar. A further weakness is that these meta-analyses did not report any cohorts of patients who had a significant stenosis but had a CABG alone (other than prior to delayed CEA). Gaudino et al. in 2001 reported 5 year follow up of a small cohort of 139 asymptomatic patients undergoing CABG alone compared to CEA and CABG. There was only one perioperative stroke in each group, but by 5 years 17 patients (24%) who did not have CEA had a stroke, compared to only one patient in the treatment group. We found no further studies such as this, however, with medium term follow up after these two strategies.
The studies into lone asymptomatic carotid stenosis are, however, impressive. In 2004 the Asymptomatic Carotid Surgery Trial (ACST) [7] reported their medium term results from 3120 patients randomised from 126 centres in 30 countries. They found that Carotid endarterectomy in asymptomatic stenosis led to a 5-year stroke rate of 6.4% compared to a stroke rate of 11.8% in patients randomised to the control group (P<0.0001).
This study supported the findings of the Asymptomatic Carotid Atherosclerosis Study [5] in 1995, that showed in a study of 1662 patients that those who had an endarterectomy had a 5-year incidence of stroke of 5% compared to 11% in the control group. These two RCTs contradicted a previous large cohort study by the European Carotid Surgery trialists collaborative who performed a sub-analysis of their RCT and found that those with an untreated carotid stenosis had only a 5.7% risk of stroke at 3 years and concluded that the benefit of surgical intervention would probably be contra-indicated. Finally, a Cochrane review in 2004 [6] combined these two RCTs with 4 further RCTs to show a small benefit in favour of Carotid endarterectomy for asymptomatic stenosis.
The third area of evidence is that of guidelines. The American Heart Association has provided two relevant guidelines in this area in 1998 and 2004 [10, 11]. In 1998 the AHA provided guidelines for carotid endarterectomy. They concluded that in patients with an operative mortality of <3% and an expected life expectancy of more than 5 years requiring CABG with an asymptomatic carotid stenosis of more than 60%, carotid endarterectomy was not a proven indication but was an acceptable indication (based on grade C evidence). Patients with higher mortality may also have an acceptable indication if bilateral stenoses were present. This was also supported in the 2004 guidelines on coronary bypass grafting, where the AHA concluded that endarterectomy is ‘probably’ indicated in asymptomatic stenoses over 80% (based on grade C evidence).
Therefore based on the above evidence, it is clear that lower risk patients with a significant asymptomatic carotid stenosis should be considered for carotid entarterectomy at some stage. When coronary arterial surgery is also required it is far less clear as to when the endarterectomy should be performed, and there is no strong evidence that this should be performed prior to, or during the coronary arterial bypass procedure.
7. Clinical bottom line
Low risk, younger patients with a significant asymptomatic carotid artery stenosis should be considered for carotid endarterectomy at some stage. There is, however, no strong evidence that this must be performed prior to, or during CABG.
References
Dunning J, Prendergast B, Mackway-Jones K. Towards evidence based medicine in cardiothoracic surgery: best BETS. Interact CardioVasc Thorac Surg 2003;2:405–409.
Naylor R, Cuffe RL, Rothwell PM, Loftus IM, Bell PR. A systematic review of outcome following synchronous carotid endarterectomy and coronary artery bypass: influence of surgical and patient variables. Eur J Vasc Endovasc Surg 2003;26:230–241.
Gaudino M, Glieca F, Luciani N, Cellini C, Morelli M, Spatuzza P, Di Mauro M, Alessandrini F, Possati G. Should severe monolateral asymptomatic carotid artery stenosis be treated at the time of coronary artery bypass operation Eur J Cardiothorac Surg 2001;19:619–626.
Randomised trial of endarterectomy for recently symptomatic carotid stenosis: final results of the MRC European Carotid Surgery Trial (ECST). Lancet 1998;351:1379–1387.
. Executive Committee for the Asymptomatic Carotid Atherosclerosis Study. Endarterectomy for asymptomatic carotid artery stenosis. J Am Med Assoc 1995;273:1421–1428.
Chambers BR, You RX, Donnan GA. Carotid endarterectomy for asymptomatic carotid stenosis (Cochrane Review). The Cochrane Library 2004;Chichester, UK: John Wiley & Sons, Ltd In:.
. The European Carotid Surgery Trialists Collaborative Group. Risk of stroke in the distribution of an asymptomatic carotid artery. Lancet 1995;345:209–212.
Das SK, Brow TD, Pepper J. Continuing controversy in the management of concomitant coronary and carotid disease: an overview. Int J Cardiol 2000;74:47–65.
Borger MA, Fremes SE, Weisel RD, Cohen G, Rao V, Lindsay TF, Naylor CD. Coronary Bypass and Carotid Endarterectomy: Does a Combined Approach Increase Risk A Metaanalysis. Ann Thorac Surg 1999;68:14–21.
Biller J, Feinberg WM, Castaldo JE, Whittemore AD, Harbaugh RE, Dempsey RJ, Caplan LR, Kresowik TF, Matchar DB, Toole JF, Easton JD, Adams HP. Guidelines for carotid endarterectomy: a statement for healthcare professionals from a special writing group of the stroke Council. American Heart Association Circulation Feb 1998;97:501–509.(Michael O. Murphy, Jonath)