Kamal, Ayeesha Kamran

Khan, Maria

eCommons@AKU

eCommons@AKUDepartment of Medicine Department of MedicineAugust 2010How should physicians practically approachsymptomatic and asymptomatic carotid stenosis?Maria KhanAga Khan UniversityAyeesha Kamran KamalAgha Khan University, ayeesha.kamal@aku.eduFollow this and additional works at: http://ecommons.aku.edu/pakistan_fhs_mc_med_medPart of the Neurology CommonsRecommended CitationKhan, M., Kamal, A. (2010). How should physicians practically approach symptomatic and asymptomatic carotid stenosis?. JPMA.The Journal of the Pakistan Medical Association, 60(8), 696-697.Available at: http://ecommons.aku.edu/pakistan_fhs_mc_med_med/390The North American Symptomatic CarotidEndarterectomy Trial-NASCET AND Asymptomatic CarotidAtherosclerosis Study-ACAS:Why are these studies important andnoteworthy?Carotid endarterectomy was first introduced in NorthAmerica in 1954 and since then surgeons were performing thisprocedure for stroke prevention without much evidence of itsefficacy. In 1988 the NASCET investigators set out todetermine if CE was beneficial in patients with carotid stenosisand TIA or partial stroke, in other words symptomatic patients.The same questions applied to patients who had noprior history of TIA or infarction. Therefore in 1987, theACAS investigators designed a study to find out whether theaddition of CE to aspirin plus risk factor modifications willaffect the incidence of TIA or infarctions in patients withasymptomatic but haemodynamically significant carotidstenosis in at least one artery.In the Pakistani perspective, it is important to knowwhat kind of benefits can be expected from such an invasiveprocedure, and what should be the acceptable risk whileundertaking them. Who were the participants?NASCET was conducted at 50 centers across USAand Canada for severe disease and patients with moderatedisease were recruited from 106 centers. The selection ofthese centers was based on very stringent criteria. Each centerhad a rate of <6% for stroke and death occurring within 30days of operation for at least 50 consecutive CE performedwithin the previous 24 months. Six hundred and sixty twopatients with high-grade stenosis were enrolled betweenJanuary 1, 1988 and February 21, 1991. At this point,randomization of patients with high grade stenosis wasterminated due to evidence of treatment efficacy with CE.These were patients who had experienced within the past 120days, one or more TIA or minor stroke, and had ipsilateralstenosis of more than 30% and less than 100%. Patients whowere 80 years of age or more and who had risk factors forcardioembolic strokes were excluded. For the moderatestenosis group, patients were eligible if they had symptoms offocal cerebral ischaemia ipsilateral to a stenosis of 50-70percent in the ICA, within 180 days, as shown on selectiveangiography. Octagenerians were not excluded from this part.Of the 2226 patients with moderate stenosis, 1118 wereassigned to medical therapy and 1108 got surgical therapy.There were 858 eligible patients with 50-69% stenosis, and1368 had <50% stenosis.ACAS was carried out at 39 centers across the USA.Candidates were eligible who were between the ages of 40and 79 years and who had unilateral or bilateral surgicallyaccessible stenosis of the region of the bifurcation of thecommon or internal carotid artery of at least 60%. Those whohad history of TIA or stroke were excluded. During the 6years of the study, more than 42,000 patients were screenedand 1662 patients were randomized, 825 to the surgical armand 834 to the medical arm.What was the intervention?In NASCET participating physicians applied the bestavailable medical therapy to all treatable risk factors in allpatients: Antiplatelet with 1300mg Aspirin per day or a lowerdose if necessitated by side effects and antihypertensive, antilipid and anti diabetic therapy for all requiring it. Those in thesurgical arm also underwent CE, the procedure of which wasleft to the surgeon's discretion. In ACAS, All patients received 325 mg of regular orenteric-coated aspirin daily. Stroke risk factors and theirmodification were reviewed with all patients at the time ofrandomization and again during subsequent interviews andtelephone follow-ups. This included discussion of diastolicand systolic hypertension, diabetes mellitus, abnormal lipidlevels, excessive consumption of ethanol, and tobacco use. Inaddition, patients randomized to the surgical arm received thenormal evaluation and care of a surgical patient. They werescheduled to undergo CEA within 2 weeks of randomization.What was the outcome?In NASCET, 69% of the patients were males, morethan 90% were whites and 69% had TIA as the entry event.Hypertension was the predominant risk factor being presentin around 60% whereas diabetes was only there in less than20% of the patients. The risk of any fatal or non fatalipsilateral stroke by 24 months after randomization was 26%for the medical patients and only 9% for the surgical patients,696 J Pak Med AssocEvidence Based MedicineHow should physicians practically approach symptomaticand asymptomatic carotid stenosis?Maria Khan, Ayeesha Kamran KamalStroke Service and Vascular Fellowship Program, Aga Khan University Hospital, Stadium Road, Karachi, Pakistan.translating to an absolute risk reduction of 17% and a relativerisk reduction of 64% with surgery. The surgical patients hadan early disadvantage, because of the risk of perioperativestroke and death which was 1.2% but this was offset by anabsolute risk reduction of 10.6% of any major stroke or deathover the next two years. A secondary analysis showed thatfiner divisions of the degree of high-grade stenosis correlatedwith the degrees of risk reduction after surgery.For the primary analysis of any fatal or nonfatalipsilateral stroke, in the moderate stenosis group of NASCET,the five-year failure rate for patients with 50 to 69 percentstenosis was 22.2 percent for medically treated patients and15.7 percent for surgically treated patients (P=0.045). Thismeant an absolute risk reduction of 6.5% and a relative riskreduction of 29%. Also 15 patients would need to be treatedby endarterectomy to prevent one ipsilateral stroke at fiveyears. For patients with stenosis of less than 50 percent, thecorresponding five-year failure rates were 18.7 percent formedically treated patients and 14.9 percent for surgicallytreated patients (P=0.16).In ACAS as well, more than 80% of the patients wereabove 60, 66% were males, and more than 90% were white.Hypertension was again the commonest risk factor, with DMpresent in only 20% of the patients. For the surgical group,the risk in the perioperative period was 2.3% (95% CI, 1.28%to 3.32%), whereas for the medical group it was 0.4% (95%CI, 0.0% to 0.8%). All patients randomized to the surgicalgroup were required to have arteriography. Of the 414patients who underwent arteriography prior to CEA, fiveexperienced a cerebral infarction, for an artériographiccomplication rate of 1.2%. The study achieved itssignificance after a median of 2.7 years of follow-up. Theestimated 5-year risk of ipsilateral stroke and anyperioperative stroke or death was 11.0% for the medicalgroup and 5.1% for the surgical group. The reduction in 5-year ipsilateral stroke risk in the surgical group was 53% ofthe estimated 5-year risk in the medical group (p=0.004).Although not statistically significant, men had a betteroutcome with surgery then women with fewer operativecomplications.What were the conclusions?NASCET and ACAS were two large trials carried outin patients with carotid stenosis. The NASCET shows thatsymptomatic patients with carotid stenosis of >70% derivesubstantial benefit from CE that persists for more than 5years. Those with stenosis between 50-70% benefit less, andthose with stenosis <50% derive no advantage from surgery. ACAS evaluated asymptomatic patients and showedthat those with greater than 60% stenosis benefit from CE,with evidence of benefit being more robust in men than inwomen.How does this impact our clinical practice?Before NASCET and ACAS, carotidendarterectomies were being performed without muchevidence of their long term benefits. These two trials not justprovided this evidence but also laid down standards forperioperative care in CE. In Pakistan, carotid disease is not such a major riskfactor. But in those who have the disease, surgery is definitelyadvisable for symptomatic individuals with greater than 70%stenosis, and perhaps also in those with moderate stenosis.For asymptomatic individuals again, it can be considered inmen with greater than 60% stenosis. However, what must bekept in mind is that the benefit will only be realized at a centeroffering an angiography complication rate in the range of1.2% and a carotid endarterectomy complication rate in therange of 2.1%. With higher rates of complications, the benefitwill diminish. Also NASCET showed that if they have norecurring symptoms, patients have little to gain fromendarterectomy after two to three years of the initial event.We should offer this procedure to patients in centerswhere the perioperative complications are regularly audited.Recommended Reading1. The North American Symptomatic Carotid Endarterectomy Trial Collaborators.Beneficial beffect of carotid endarterectomy in symptomatic patients with high-grade carotid stenosis. N Engl J Med 1991; 325: 445-53.2. Benefit of carotid endarterectomy in patients with symptomatic moderate orsevere stenosis. North American Symptomatic Carotid Endarterectomy TrialCollaborators. Barnett HJ, Taylor DW, Eliasziw M, Fox AJ, Ferguson GG et al.N Engl J Med 1998; 339: 1415-25.3. Endarterectomy for asymptomatic carotid artery stenosis. ExecutiveCommittee for the Asymptomatic Carotid Atherosclerosis Study. JAMA 1995;273: 1421-8.4. Wasay M, Azeemuddin M, Masroor I, Sajjad Z, Ahmed R, Khealani BA, MalikMA, Afridi MB, Kamal A. Frequency and outcome of carotid atheromatousdisease in patients with stroke in Pakistan.Stroke. 2009; 40: 708-12.Vol. 60, No. 8, August 2010 697

English

How should physicians practically approach symptomatic and asymptomatic carotid stenosis?

eCommons@AKUSection of Neurology Department of MedicineAugust 2010How should physicians practically approachsymptomatic and asymptomatic carotid stenosisMaria KhanAga Khan UniversityAyeesha Kamran KamalAga Khan UniversityFollow this and additional works at: http://ecommons.aku.edu/pakistan_fhs_mc_med_neurolPart of the Neurology CommonsRecommended CitationKhan, M., Kamal, A. (2010). How should physicians practically approach symptomatic and asymptomatic carotid stenosis. Journal ofthe Pakistan Medical Association, 60(8), 696-7.Available at: http://ecommons.aku.edu/pakistan_fhs_mc_med_neurol/22The North American Symptomatic CarotidEndarterectomy Trial-NASCET AND Asymptomatic CarotidAtherosclerosis Study-ACAS:Why are these studies important andnoteworthy?Carotid endarterectomy was first introduced in NorthAmerica in 1954 and since then surgeons were performing thisprocedure for stroke prevention without much evidence of itsefficacy. In 1988 the NASCET investigators set out todetermine if CE was beneficial in patients with carotid stenosisand TIA or partial stroke, in other words symptomatic patients.The same questions applied to patients who had noprior history of TIA or infarction. Therefore in 1987, theACAS investigators designed a study to find out whether theaddition of CE to aspirin plus risk factor modifications willaffect the incidence of TIA or infarctions in patients withasymptomatic but haemodynamically significant carotidstenosis in at least one artery.In the Pakistani perspective, it is important to knowwhat kind of benefits can be expected from such an invasiveprocedure, and what should be the acceptable risk whileundertaking them. Who were the participants?NASCET was conducted at 50 centers across USAand Canada for severe disease and patients with moderatedisease were recruited from 106 centers. The selection ofthese centers was based on very stringent criteria. Each centerhad a rate of <6% for stroke and death occurring within 30days of operation for at least 50 consecutive CE performedwithin the previous 24 months. Six hundred and sixty twopatients with high-grade stenosis were enrolled betweenJanuary 1, 1988 and February 21, 1991. At this point,randomization of patients with high grade stenosis wasterminated due to evidence of treatment efficacy with CE.These were patients who had experienced within the past 120days, one or more TIA or minor stroke, and had ipsilateralstenosis of more than 30% and less than 100%. Patients whowere 80 years of age or more and who had risk factors forcardioembolic strokes were excluded. For the moderatestenosis group, patients were eligible if they had symptoms offocal cerebral ischaemia ipsilateral to a stenosis of 50-70percent in the ICA, within 180 days, as shown on selectiveangiography. Octagenerians were not excluded from this part.Of the 2226 patients with moderate stenosis, 1118 wereassigned to medical therapy and 1108 got surgical therapy.There were 858 eligible patients with 50-69% stenosis, and1368 had <50% stenosis.ACAS was carried out at 39 centers across the USA.Candidates were eligible who were between the ages of 40and 79 years and who had unilateral or bilateral surgicallyaccessible stenosis of the region of the bifurcation of thecommon or internal carotid artery of at least 60%. Those whohad history of TIA or stroke were excluded. During the 6years of the study, more than 42,000 patients were screenedand 1662 patients were randomized, 825 to the surgical armand 834 to the medical arm.What was the intervention?In NASCET participating physicians applied the bestavailable medical therapy to all treatable risk factors in allpatients: Antiplatelet with 1300mg Aspirin per day or a lowerdose if necessitated by side effects and antihypertensive, antilipid and anti diabetic therapy for all requiring it. Those in thesurgical arm also underwent CE, the procedure of which wasleft to the surgeon's discretion. In ACAS, All patients received 325 mg of regular orenteric-coated aspirin daily. Stroke risk factors and theirmodification were reviewed with all patients at the time ofrandomization and again during subsequent interviews andtelephone follow-ups. This included discussion of diastolicand systolic hypertension, diabetes mellitus, abnormal lipidlevels, excessive consumption of ethanol, and tobacco use. Inaddition, patients randomized to the surgical arm received thenormal evaluation and care of a surgical patient. They werescheduled to undergo CEA within 2 weeks of randomization.What was the outcome?In NASCET, 69% of the patients were males, morethan 90% were whites and 69% had TIA as the entry event.Hypertension was the predominant risk factor being presentin around 60% whereas diabetes was only there in less than20% of the patients. The risk of any fatal or non fatalipsilateral stroke by 24 months after randomization was 26%for the medical patients and only 9% for the surgical patients,696 J Pak Med AssocEvidence Based MedicineHow should physicians practically approach symptomaticand asymptomatic carotid stenosis?Maria Khan, Ayeesha Kamran KamalStroke Service and Vascular Fellowship Program, Aga Khan University Hospital, Stadium Road, Karachi, Pakistan.translating to an absolute risk reduction of 17% and a relativerisk reduction of 64% with surgery. The surgical patients hadan early disadvantage, because of the risk of perioperativestroke and death which was 1.2% but this was offset by anabsolute risk reduction of 10.6% of any major stroke or deathover the next two years. A secondary analysis showed thatfiner divisions of the degree of high-grade stenosis correlatedwith the degrees of risk reduction after surgery.For the primary analysis of any fatal or nonfatalipsilateral stroke, in the moderate stenosis group of NASCET,the five-year failure rate for patients with 50 to 69 percentstenosis was 22.2 percent for medically treated patients and15.7 percent for surgically treated patients (P=0.045). Thismeant an absolute risk reduction of 6.5% and a relative riskreduction of 29%. Also 15 patients would need to be treatedby endarterectomy to prevent one ipsilateral stroke at fiveyears. For patients with stenosis of less than 50 percent, thecorresponding five-year failure rates were 18.7 percent formedically treated patients and 14.9 percent for surgicallytreated patients (P=0.16).In ACAS as well, more than 80% of the patients wereabove 60, 66% were males, and more than 90% were white.Hypertension was again the commonest risk factor, with DMpresent in only 20% of the patients. For the surgical group,the risk in the perioperative period was 2.3% (95% CI, 1.28%to 3.32%), whereas for the medical group it was 0.4% (95%CI, 0.0% to 0.8%). All patients randomized to the surgicalgroup were required to have arteriography. Of the 414patients who underwent arteriography prior to CEA, fiveexperienced a cerebral infarction, for an artériographiccomplication rate of 1.2%. The study achieved itssignificance after a median of 2.7 years of follow-up. Theestimated 5-year risk of ipsilateral stroke and anyperioperative stroke or death was 11.0% for the medicalgroup and 5.1% for the surgical group. The reduction in 5-year ipsilateral stroke risk in the surgical group was 53% ofthe estimated 5-year risk in the medical group (p=0.004).Although not statistically significant, men had a betteroutcome with surgery then women with fewer operativecomplications.What were the conclusions?NASCET and ACAS were two large trials carried outin patients with carotid stenosis. The NASCET shows thatsymptomatic patients with carotid stenosis of >70% derivesubstantial benefit from CE that persists for more than 5years. Those with stenosis between 50-70% benefit less, andthose with stenosis <50% derive no advantage from surgery. ACAS evaluated asymptomatic patients and showedthat those with greater than 60% stenosis benefit from CE,with evidence of benefit being more robust in men than inwomen.How does this impact our clinical practice?Before NASCET and ACAS, carotidendarterectomies were being performed without muchevidence of their long term benefits. These two trials not justprovided this evidence but also laid down standards forperioperative care in CE. In Pakistan, carotid disease is not such a major riskfactor. But in those who have the disease, surgery is definitelyadvisable for symptomatic individuals with greater than 70%stenosis, and perhaps also in those with moderate stenosis.For asymptomatic individuals again, it can be considered inmen with greater than 60% stenosis. However, what must bekept in mind is that the benefit will only be realized at a centeroffering an angiography complication rate in the range of1.2% and a carotid endarterectomy complication rate in therange of 2.1%. With higher rates of complications, the benefitwill diminish. Also NASCET showed that if they have norecurring symptoms, patients have little to gain fromendarterectomy after two to three years of the initial event.We should offer this procedure to patients in centerswhere the perioperative complications are regularly audited.Recommended Reading1. The North American Symptomatic Carotid Endarterectomy Trial Collaborators.Beneficial beffect of carotid endarterectomy in symptomatic patients with high-grade carotid stenosis. N Engl J Med 1991; 325: 445-53.2. Benefit of carotid endarterectomy in patients with symptomatic moderate orsevere stenosis. North American Symptomatic Carotid Endarterectomy TrialCollaborators. Barnett HJ, Taylor DW, Eliasziw M, Fox AJ, Ferguson GG et al.N Engl J Med 1998; 339: 1415-25.3. Endarterectomy for asymptomatic carotid artery stenosis. ExecutiveCommittee for the Asymptomatic Carotid Atherosclerosis Study. JAMA 1995;273: 1421-8.4. Wasay M, Azeemuddin M, Masroor I, Sajjad Z, Ahmed R, Khealani BA, MalikMA, Afridi MB, Kamal A. Frequency and outcome of carotid atheromatousdisease in patients with stroke in Pakistan.Stroke. 2009; 40: 708-12.Vol. 60, No. 8, August 2010 697

How should physicians practically approach symptomatic and asymptomatic carotid stenosis

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How should physicians practically approach symptomatic and asymptomatic carotid stenosis

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