CME

Management of carotid artery stenosis

Update for family physicians
George Louridas, MB BCH(WITS), FCS(SA), MMED(SURG), FACS Asad Junaid, MD, FRCPC

ABSTRACT
OBJECTIVE To clarify the definition of carotid artery diseases, the appropriateness of screening for disease, investigation and
management of patients presenting with transient ischemic attacks, and management of asymptomatic carotid bruits.
SOURCES OF INFORMATION MEDLINE was searched using the terms carotid endarterectomy, carotid disease, and carotid
stenosis. Most studies offer level II or III evidence. Consensus statements and guidelines from various neurovascular societies
were also consulted.
MAIN MESSAGE Patients with symptoms of hemispheric transient ischemic attacks associated with >70% stenosis of the
internal carotid artery are at highest risk of major stroke or death. Risk is greatest within 48 hours of symptom onset; patients
should have urgent evaluation by a vascular surgeon for consideration of carotid endarterectomy (CEA). Patients with 50%
to 69% stenosis might benefit from urgent surgical intervention depending on clinical features and associated comorbidity.
Patients with <50% stenosis do not benefit from surgery. Asymptomatic patients with >60% stenosis should be considered for
elective CEA.
CONCLUSION Symptomatic carotid artery syndromes need urgent carotid duplex evaluation to determine the need for urgent
surgery. Those with the greatest degree of stenosis derive the greatest benefit from timely CEA.
RÉSUMÉ
OBJECTIF Clarifier la définition des maladies carotidiennes, les indications du dépistage, l’investigation et le traitement des
épisodes d’ischémie transitoire, et le traitement des souffles carotidiens asymptomatiques.
SOURCE DE L’INFORMATION Une recherche a été effectuée dans MEDLINE à l’aide des termes carotid endarterectomy, carotid
disease et carotid stenosis. La plupart des études offrent des preuves de niveaux II et III. Les déclarations consensuelles et les
directives de diverses associations neurovasculaires ont aussi été consultées.
PRINCIPAL MESSAGE Les patients qui présentent des épisodes d’ischémie hémisphérique transitoire associés à une sténose
de la carotide interne de >70% présentent le plus haut risque d’accident vasculaire cérébral et de mort. Ce risque est maximal
dans les 48 heures suivant le début des symptômes; le patient doit être évalué d’urgence par un chirurgien vasculaire pour
une éventuelle endartériectomie carotidienne (EC). Ceux qui ont une sténose entre 50 et 69% pourraient bénéficier d’une
intervention chirurgicale urgente, selon les caractéristiques cliniques et la présence de comorbidité. Les sténoses de <50%
n’ont pas avantage à être opérées. Dans les sténoses de >60%, une EC élective devrait être envisagée.
CONCLUSION Les syndromes carotidiens symptomatiques requièrent une échographie bidimensionnelle rapide pour
déterminer l’urgence d’intervenir. Les sténoses les plus serrées bénéficient le plus d’une EC faite à temps.

This article has been peer reviewed.

Cet article a fait l’objet d’une révision par des pairs.
Can Fam Physician 2005;51:984-989.

984 Canadian Family Physician • Le Médecin de famille canadien d VOL 5: JULY • JUILLET 2005

S
troke is the third most common cause of
death worldwide after ischemic heart disease
and cancer. Approximately 30% of patients die
within the first year of having a stroke and another
50% are left disabled. The morbidity of a stroke is
devastating. We hope a more aggressive approach
to management will improve outcomes. Common
causes of stroke are listed in Table 1.1
Table 1. Common causes of stroke
CAUSE % OF STROKES
Ischemic stroke 80
• Atheroembolism 50
• Intracranial small vessel disease 25
• Cardiac source 20
• Rare causes 5
Primary intracerebral hemorrhage 15
Subarachnoid hemorrhage 5
Extracranial carotid disease (carotid stenosis)
accounts for at least 50% of ischemic strokes and
should be managed efficiently to minimize the inci-
dence of stroke. Unfortunately, only about 15% of
strokes are preceded by transient ischemic attacks
(TIAs). 2 Until recently, North American guide-
lines recommended that assessment and investiga-
tion be completed within 1 week of a TIA,3,4 and
British guidelines recommended assessment within
2 weeks.5,6 New evidence now suggests that earlier
evaluation is needed.
Once an acute TIA is clinically diagnosed,
carotid imaging should be performed immedi-
ately, and if indicated, patients should be referred
for urgent carotid endarterectomy (CEA). Two
major randomized trials have confirmed that
symptomatic patients benefit from CEA (level
I evidence).7,8 Risk of stroke following a TIA is
5.5% at 48 hours, 8.0% to 10.3% at 7 days, 11.5%
to 14.3% at 30 days, and 17.3% to 20.1% at 90
days (level II).9-13
Dr Louridas is an Associate Professor and Section Head
of Vascular Surgery, and Dr Junaid is an Assistant
Professor and Head of Vascular Medicine, at the
University of Manitoba Health Sciences Centre and at St
Boniface General Hospital in Winnipeg.
VOL 5: JULY • JUILLET 2005 d Canadian Family Physician • Le Médecin de famille canadien
Management of carotid artery stenosis CME
Current data also confirm that asymptom-
atic patients aged 75 years or younger with >60%
carotid stenosis are likely to benefit from CEA
(level I). 14 Family physicians and emergency
room physicians can greatly affect the outcomes
of these patients, as they are often the first to
evaluate them.
Quality of evidence
MEDLINE was searched using the terms carotid
endarterectomy, carotid disease, and carotid ste-
nosis. Consensus statements and guidelines from
various neurovascular societies were also sought.
Most of the evidence is level I or II.
Levels of evidence
Level I: At least one properly conducted random-
ized controlled trial, systematic review, or meta-
analysis
Level II: Other comparison trials, non-randomized,
cohort, case-control, or epidemiologic studies,
and preferably more than one study
Level III: Expert opinion or consensus statements
Definitions
Stroke is defined by the World Health Organization
as the clinical syndrome of rapid onset of a focal (or
global, as in subarachnoid hemorrhage) cerebral defi-
cit that lasts more than 24 hours or leads to death,
with no apparent cause other than a vascular one.
Transient ischemic attack is a sudden, focal neurologic
deficit that lasts less than 24 hours. Most symptoms
of TIA last from a few seconds to 5 to 10 minutes,
and 75% of symptoms resolve within 1 hour.1, 15,16
The proposed new definition of TIA is a brief
episode of neurologic dysfunction caused by focal
brain or retinal ischemia, with clinical symptoms
typically lasting less than 1 hour and no evidence
of acute infarction. The corollary is that persistent
clinical signs or characteristic imaging abnormalities
of infarction detected by computerized tomography
(CT) or magnetic resonance imaging (MRI) consti-
tute a stroke.17
985
CME Management of carotid artery stenosis

Screening significant lesions (70% to 90% stenosis). Among

The prevalence of >50% carotid artery stenosis in patients with significant hemodynamic carotid ste-
the general population is too low to justify wide- nosis, only 50% have a bruit noted during physical
spread screening for this condition (level I).18 About examination. The annual incidence of stroke among
35% of patients with a carotid bruit have >50% ste- those with asymptomatic bruits but no prior TIA is
nosis. Therefore, carotid arteries should be aus- 1% to 3% (level II).21-23
cultated as part of routine physical examinations
Table 2. Carotid symptoms compared with vertebrobasilar
in the general adult population. Those found to symptoms
have carotid bruits should be further evaluated by SYNDROME CAROTID TERRITORY VERTEBROBASILAR TERRITORY
duplex scans. Patients with symptomatic coronary Motor defect Weakness or paralysis Weakness or paralysis on
artery disease have a 22% incidence of carotid ste- on contralateral side contralateral side
nosis >50% and an 8% to 12% incidence of carotid Sensory defect Numbness, loss of Numbness, including loss of
stenosis >70%.19 sensation, or sensation or paresthesiae,
Patients with peripheral arterial disease have a paresthesiae on bilateral or shifting
contralateral side
14% incidence of carotid artery stenosis >50% (level
Speech defect Dysarthria* or Dysarthria with other brain
II).20 Given the relatively limited access to duplex dysphasia† stem signs
scanning, however, we cannot advocate screening
Vision defect Unilateral blindness Loss of vision, complete or
these patients for asymptomatic carotid disease. (amaurosis fugax) on partial in both homonymous
This is based on the idea that these patients are ipsilateral side; fields
likely already receiving medical therapy for athero- complete ipsilateral
blindness; central
sclerosis and, given their underlying disease, are not retinal artery occlusion;
in a low-risk category for carotid artery surgery. central retinal artery
branch occlusion
Carotid artery disease presentations Ataxia ... Imbalance, unsteadiness, or
disequilibrium, not associated
Symptomatic disease. Classic symptoms of TIA
with vertigo
are contrasted with vertebrobasilar symptoms in
Drop attacks ... Episodic loss of muscle tone
Table 2. Although not always possible, it is impor- without alterations in
tant to distinguish between these two types of symp- consciousness*
toms because patients with transient ischemia of the *Imperfect articulation of speech due to disturbance of muscular control.
†Speech impairment from lack of coordination and failure to arrange words in proper order.
vertebrobasilar system do not benefit from CEA.
Patients presenting with motor weakness, speech
deficit, hemispatial deficit, or hemianopia, alone Management
or in combination, are at high risk (5%) of hav- An approach to managing carotid artery stenosis is
ing a stroke within 48 hours even with medical shown in Figure 1.
management (level II).9,10,12,13 Patients who present
with sensory deficits and amaurosis fugax are at Symptomatic disease. Patients presenting to their
low risk (0%) of stroke within 48 hours (level II).10 family physicians with a TIA should immediately
Risk of stroke at 90 days in symptomatic patients is be given acetylsalicylic acid (80 to 325 mg). Patients
between 8% and 20.1% (level II).9,11-13 who have a TIA while taking ASA should be given
clopidogrel. High-risk patients presenting within a
Asymptomatic carotid bruit. Asymptomatic few hours of onset of symptoms of a TIA should
carotid artery stenosis is usually detected by a undergo urgent duplex scanning. If a >70% stenosis
physician auscultating a patient’s carotid arteries is detected in the carotid artery contralateral to the
and hearing a bruit or coincidentally during ultra- side of somatic symptoms, patients should immedi-
sound examination of the neck. Among patients ately be evaluated by a vascular surgeon with a view
with carotid bruit, only 35% have hemodynamically to having CEA within 48 hours of presentation.

986 Canadian Family Physician • Le Médecin de famille canadien d VOL 5: JULY • JUILLET 2005
 Management of carotid artery stenosis CME

Figure 1. Management of carotid artery stenosis: High-risk patients present with symptoms of motor weakness, speech deficit, hemispatial
deficit, and hemianopia; low-risk patients present with only sensory deficit or amaurosis fugax.

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High-risk patients who present after 48 hours had a stroke within the last 3 months, and had
but within 7 days should have CEA within 7 days hemispheric symptoms. Patients who benefited
of onset of symptoms. Patients presenting between from medical therapy were those with less severe
7 days and 30 days after a TIA should have sur- stenosis, were younger than 75, were women, had
gery within 30 days; patients presenting between 30 had a stroke more than 3 months ago, and had
and 90 days after symptom onset should have sur- visual symptoms. Number needed to treat to pre-
gery within 90 days. Recent studies have shown that vent one stroke at 5 years was 12 for men and 67
high-risk patients are likely to benefit from CEA as for women (level I).26 Symptomatic patients with
early as possible up to 90 days after an initial TIA <50% stenosis did not benefit from surgical inter-
(level II).9-13 Patients presenting 90 days or more after vention (level I).26
onset of symptoms could be offered elective CEA. The main reason for routine brain CT scanning
Low-risk patients (amaurosis fugax, sensory def- after a TIA is to exclude causes such as tumour,
icit only) should have an elective CEA within 90 arteriovenous malformation, hydro cephalus,
days (level II).24,25 Two randomized controlled trials intracranial aneurysm, or sufficient hemorrhage
confirmed the benefit of surgery over medical ther- to contraindicate surgical treatment. The yield
apy for patients with symptoms and >70% carotid of this test is <1%.27 In fact, ipsilateral CT scan
stenosis (level I).7,8 Number needed to treat to defects were found in 20% of patients who had
prevent one stroke at 2 years is nine. Symptomatic asymptomatic carotid stenosis and in 33% of
patients with 50% to 69% carotid stenosis benefited patients with a history of TIA. Defects seen were
marginally from surgery. all infarcts. No tumours, arteriovenous malforma-
The patients who benefited from CEA had more tions, or any other intracranial abnormalities were
severe stenosis, were 75 or older, were men, had detected.28 Management of patients with TIAs and

VOL 5: JULY • JUILLET 2005 d Canadian Family Physician • Le Médecin de famille canadien 987
CME Management of carotid artery stenosis

corresponding carotid stenosis was not changed Table 3. Relative risk reduction for stroke: Beneficial effects of
by knowing the results of preoperative CT brain preventive therapy.
scans, so routine scans are unnecessary for this PREVENTIVE MANEUVER RELATIVE RISK REDUCTION (%)
population.29 Acetylsalicylic acid 16
Lipid lowering 25
Asymptomatic carotid stenosis Angiotensin-converting enzyme inhibition 32
Patients who have >60% carotid stenosis might
Hypertension control 28
benefit from CEA. Two randomized studies have
Smoking cessation 33
confirmed this benefit (level I).14,30 Surgeons who
Combined therapy ≥80
perform this surgery, however, must themselves
have a perioperative stroke rate of <3%. Patients
should be medically fit to undergo this surgery; Table 4. Acceptable risks associated with carotid endarterectomy
INDICATION FOR CAROTID ENDARTERECTOMY RISK OF STROKE AND DEATH (%)
their risk of adverse perioperative cardiovascular
Symptoms of carotid disease 5.1
events should be low.
(overall)
Urgent surgery* 19.3
What is the best medical therapy?
Stroke 7.1
Aggressive medical therapy has been shown to
Transient ischemic attack 5.5
reduce atherosclerotic carotid artery stenosis and
Ocular event 2.8
prevent symptoms.31 Antiplatelet therapy has been
shown to reduce risk of fatal stroke by 16% and No symptoms 2.8
non-fatal stroke by 28%.32 Combined ASA and war- Repeat surgery 4.4
farin therapy at an international normalized ratio of *Crescendo transient ischemic attacks, evolving stroke.

1.8 in patients with sinus rhythm proved no better

than ASA alone.33 Lipid-lowering therapy reduced
risk of stroke by 25%. 34 Angiotensin-converting
enzyme inhibitors decreased stroke rates by 32%35-
37
and were also shown to slow progression of ath-
erosclerosis in general.38
Effective management of hypertension decreases
stroke rates by 28% to 40%. 39-41 Smoking cessa-
tion has been shown to decrease women’s risk of
stroke by 48%.42-46 Table 3 summarizes the bene-
fits of aggressive risk-factor reduction. Any patient
with carotid artery stenosis, whether symptomatic
or asymptomatic, should be taking the therapies
shown in Table 3. In fact, any patient with athero-
sclerotic disease (ie, carotid artery disease), periph-
eral arterial occlusive disease, or coronary artery
disease should be taking these medications.
Carotid intervention
The criterion standard intervention has been CEA.
Indications for surgery should be correlated to a
surgeon’s personal results. Acceptable results for
stroke and death following CEA are shown in
Table 4.47 Carotid angioplasty and stenting are
gaining popularity as treatments for carotid steno-
sis. Current results at 1 year are comparable to CEA
as shown by the results of the SAPPHIRE (Stenting
and angioplasty with protection in patients at high
risk for endarterectomy) study presented at the 15th
Annual Transcatheter Cardiovascular Therapeutics
Symposium in September 2003.48 Further results
from randomized trials are awaited.
Conclusion
Because they often see patients with the first signs
of cerebral ischemia, family doctors should be
aware of the criteria for, and need for, early refer-
ral for surgery, where indicated. Careful selection
of cases will help minimize the number of unneces-
sary referrals. Patients not requiring surgery could
benefit from aggressive medical management.
Competing interests
None declared
Correspondence to: Dr G. Louridas, Department of
Surgery, St Boniface General Hospital, Z3029–409 Tache

988 Canadian Family Physician • Le Médecin de famille canadien d VOL 5: JULY • JUILLET 2005

EDITOR’S KEY POINTS
• Two recent randomized controlled trials support a more aggressive
approach to referral for carotid endarterectomy in patients with
transient ischemic attacks (TIAs).
• Those with symptoms of hemispheric TIA with >70% stenosis of the
internal carotid artery are at highest risk of major stroke or death,
especially within the first 48 hours. They should be urgently evalu-
ated by a vascular surgeon.
• Patients with TIAs and 50% to 69% stenosis might benefit from sur-
gery. Those older than 75 years, men, and people with more severe
disease are at greatest risk of stroke. Those with <50% stenosis do
not benefit from surgery.
• Medical management to prevent stroke should be aggres-
sive because combined therapy can reduce strokes by up to
80%. Management includes controlling hypertension; stopping
smoking; and using antiplatelet medications, lipid-lowering agents,
and angiotensin-converting enzyme inhibitors.
POINTS DE REPÈRE DU RÉDACTEUR
• Deux essais randomisés récents recommandent d’intervenir de façon
plus agressive devant un épisode d’ischémie transitoire (ÉIT) en
demandant une consultation pour endartériectomie éventuelle.
• Ceux qui ont des symptômes d’ÉIT hémisphérique avec une sténose de
la carotide interne de >70% sont les plus à risque d’accident vasculaire
cérébral (AVC) ou de mort, particulièrement durant les 48 premières
heures. Ils devraient être évalués sans retard par un chirurgien vasculaire.
• Les sténoses entre 50 et 69% pourraient bénéficier d’une interven-
tion. Les plus de 75 ans, les hommes et les personnes qui souffrent
de maladies plus graves ont un plus fort risque d’AVC. Les sténoses
de <50% n’ont pas avantage à être opérées.
• La prévention des AVC exige une prise en charge agressive; en effet,
le traitement combiné prévient jusqu’à 80% de ces accidents. Ce trai-
tement comprend un contrôle de l’hypertension, l’arrêt du tabac, une
médication anti-plaquettaire, des agents hypocholestérolémiants et
des inhibiteurs de l’enzyme de conversion de l’angiotensine.
Ave, Winnipeg, MB R2H 2A6; telephone (204) 237-2447;
fax (204) 237-3429; e-mail glourida@sbgh.mb.ca
References
1. Warlow CP, Dennis MS, van Gijn J. What caused this transient or persisting ischaemic event? In:
Warlow CP, Dennis MS, van Gijn J, Sandrock PA, Bamford JM, Wardlaw J, editors. Stroke: a practi-
cal guide to management. Oxford, Engl: Blackwell Science; 2001. p. 223-300.
2. Hankey GJ. Impact of treatment of people with transient ischemic attacks on stroke incidence and
public health. Cerebrovasc Dis 1996;6(Supp1):26-33.
3. Feinberg WM, Albers GW, Barnett HJ, Biller J, Caplan LR, Carter LP, et al. Guidelines for the
management of transient ischemic attacks. From the Ad Hoc Committee on Guidelines for
the Management of Transient Ischemic Attacks of the Stroke Council of the American Heart
Association. Circulation 1994;89:2950-65.
4. Wolf PA, Clagett GP, Easton JD, Goldstein LB, Gorelick PB, Kelly-Hayes M, et al. Preventing isch-
emic strokes in patients with prior stroke and transient ischemic attack: a statement for healthcare
professionals from the Stroke Council of the American Heart Association. Stroke 1999;30:1991-4.
5. Intercollegiate Working Party for Stroke. National clinical guidelines for stroke. London, Engl: Royal
College of Physicians; 2000.
6. Scottish Intercollegiate Guidelines Network. SIGN guidelines: management of patients with stroke.
Edinburgh, Scotl: Scottish Intercollegiate Guidelines Network; 1997.
7. North American Symptomatic Carotid Endarterectomy Trial Collaborators. Beneficial effect of
carotid endarterectomy in symptomatic patients with a high-grade carotid stenosis. N Engl J Med
1991;325:445-53.
8. European Carotid Surgery Trialists’ Collaborative Group. Randomized trial of endarterectomy
for recent symptomatic carotid stenosis: final results of the MRC European Carotid Surgery Trial
(ECST). Lancet 1998;351:1379-87.
9. Johnston SC, Gress DR, Browner WS, Sidney S. Short-term prognosis after emergency department
diagnosis of TIA. JAMA 2000;284:2901-6.
VOL 5: JULY • JUILLET 2005 d Canadian Family Physician • Le Médecin de famille canadien
Management of carotid artery stenosis CME
10. Lovett JK, Dennis MS, Sandercock PA, Bamford J, Warlow CP, Rothwell PM. Very early risk of stroke
after a first transient ischemic attack. Stroke 2003;34:e138-42. Epub 2003 Jul 10. Available at: http://
stroke.ahajournals.org/cgi/content/fulltext3418/e138. Accessed 2005 June 7.
11. Coull AJ, Lovett JK, Rothwell PM. Population-based study of early risk of stroke after transient ischaemic
attack or minor stroke: implications for public education and organization of services. BMJ 2004;328:326-9.
12. Gladstone DJ, Kapral MK, Fang J, Laupacis A, Tu JV. Management and outcomes of transient isch-
aemic attacks in Ontario. CMAJ 2004;170:1099-104.
13. Eliasziw M, Kennedy J, Hill MD, Buchan AM, Barnett JM. Early risk of stroke after a transient isch-
aemic attack in patients with internal carotid artery disease. CMAJ 2004;170:1105-9.
14. Prevention of disabling and fatal stroke by successful carotid endarterectomy in patients without recent
neurological symptoms: randomized controlled trial. Lancet 2004;363:1491-502.
15. Advisory Council for the National Institute of Neurological Disease and Blindness, Public and
Blindness, Public Health Service. A classification and outline of cerebrovascular diseases. Neurology
1958;8:395-434.
16. Siekert RG, Whisnant JP, editors. Cerebral vascular disease: fourth conference. New York, NY:
Grune & Stratton; 1965.
17. Albers GW, Caplan LR, Easton JD, Fayad PB, Mohr JP, Saver JL, et al. Transient ischemic attack—
proposal for a new definition. N Engl J Med 2002;347:1713-6.
18. Hill AB. Should patients be screened for asymptomatic carotid artery stenosis? Can J Surg
1998;41:208-13.
19. Ernst CB, Stanley JC, editors. Current therapy in vascular surgery. 4th ed. St Louis, Mo: Mosby;
2001. p. 102.
20. Simons PC, Algra A, Eikelboom BC, Grobbee DE, van der Graaf Y. Carotid artery stenosis in
patients with peripheral arterial disease: the SMART study. SMART study group. J Vasc Surg
1999;30:519-25.
21. Chambers BR, Norris JW. Outcome in patients with asymptomatic neck bruits. N Engl J Med
1986;315:860-5.
22. Heyman A, Wilkinson WE, Heyden S, Helms MJ, Bartel AG, Karp HR, et al. Risk of stroke in
asymptomatic persons with cervical arterial bruits: a population study in Evans County, Georgia. N
Engl J Med 1980;302:838-41.
23. Meissner I, Wiebers DO, Whisnaut JP, O’Fallon WM. The natural history of asymptomatic carotid
artery lesions. JAMA 1987;258:2704-7.
24. Johnston DC, Hill MD. The patient with transient cerebral ischemia: a golden opportunity for
stroke prevention. CMAJ 2004;170:1134-7.
25. Johnston SC, Sidney S, Bernstein AL, Gress DR. A comparison of risk factors for recurrent TIA
and stroke in patients diagnosed with TIA. Neurology 2003;60(11):1871.
26. Barnett HJ, Taylor DW, Eliasziw M, Fox AJ, Ferguson GG, Haynes RB, et al. Benefit of carotid endar-
terectomy in patients with symptomatic moderate or severe stenosis. N Engl J Med 1998;339:1415-25.
27. Feinburg WM, Albers GW, Barnett HJ, Biller J, Caplan LR, Hart RG, et al. Guidelines for the
management of transient ischemic attacks. From the Ad Hoc Committee on Guidelines for
the Management of Transient Ischemic Attacks of the Stroke Council of the American Heart
Association. Circulation 1994;89:2950-65.
28. Street DL, O’Brien MS, Ricotta JJ, Ekholm SE, Ouriel K, Green RM, et al. Observations on cere-
bral computed tomography in patients having carotid endarterectomy J Vasc Surg 1988;7:798-801.
29. Martin JD, Valentine RJ, Myers SI, Rossi MB, Patterson CB, Clagett GP. Is routine CT scanning
necessary in the preoperative evaluation of patients undergoing carotid endarterectomy? J Vasc
Surg 1991;14:267-70.
30. Executive Committee for the Asymptomatic Carotid Atherosclerosis Study. Endarterectomy for
asymptomatic carotid artery stenosis. JAMA 1995;273:1421-8.
31. Sleight SP, Poloniecki J, Halliday AW; Asymptomatic Carotid Surgery Trial corroborators.
Asymptomatic carotid stenosis in patients on medical treatment alone. Eur J Vasc Endovasc Surg
2002;23:519-23.
32. Collaborative meta-analysis of randomized trials of antiplatelet therapy for prevention of death,
myocardial infarction, and stroke in high risk patients. BMJ 2002;324:71-86.
33. Redman AR, Allen LC. Warfarin versus aspirin in the secondary prevention of stroke: The WARSS
study. Curr Atheroscler Rep 2002;4:319-25.
34. Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol
lowering with simvastatin in 20,536 high-risk individuals: a randomized placebo-controlled trial.
Lancet 2002;360:7–22. Summary for patients in Curr Cardiol Rep 2002;4:486.
35. Taylor AJ, Kent SM, Flaherty PJ, Coyle LC, Markwood TT, Vernalis MN. ARBITER: Arterial biology
for the investigation of the treatment effects of reducing cholesterol: a randomized trial comparing the
effects of atorvastatin and pravastatin on carotid intima medial thickness. Circulation 2002;106:2055-60.
36. Mercuri M, Bond MG, Sirtori CR, Veglia F, Crepaldi G, Feruglio FS, et al. Pravastatin
reduces carotid intima-media thickness progression in an asymptomatic hypercholesterolemic
Mediterranean population: the Carotid Atherosclerotic Italian Ultrasound Study. Am J Med
1996;101:627-34.
37. Bosch J, Yusuf S, Pogue J, Sleight P, Lonn E, Rangoonwala B. Use of ramipril in preventing stroke:
double blind randomized trial. BMJ 2002;324:1-5.
38. Heart Outcomes Prevention Evaluation Study Investigators. Effects of ramipril on cardiovascular
and microvascular outcomes in people with diabetes mellitus: results of the HOPE study and MICRO-
HOPE substudy [published erratum appears in Lancet 2000;356:860]. Lancet 2000;355:253-9.
39. The Heart Outcomes Prevention Evaluation Study Investigators. Effects of an angiotensin-con-
verting-enzyme inhibitor, ramipril, on cardiovascular events in high risk patients. N Engl J Med
2000;342:145-53.
40. Lonn EM, Yusuf S, Dzavik V, Doris I, Yi Q, Smith S. Effects of ramipril and vitamin E on athero-
sclerosis. The study to evaluate carotid ultrasound changes in patients treated with ramipril and
vitamin E (SECURE). Circulation 2001;103:919-25.
41. Collins R, Peto R, MacMahon S, Hebert P, Fiebach NH, Eberlein KA. Blood pressure, stroke, and
coronary heart disease. Part 2. Short-term reduction in blood pressure: overview of randomized
drug trials in their epidemiological context. Lancet 1990;335:827-38.
42. PROGRESS Collaborative Group. Randomised trial of a perindopril-based blood pressure lower-
ing regimen among 6,105 individuals with previous stroke or transient ischaemic attack [published
erratum appears in Lancet 2001;358:1556 and Lancet 2002;359:2120]. Lancet 2001;358:1033-41.
Summary for patients in Can Fam Physician 2002;48:1625-9.
43. Chalmers J. Trials on blood pressure-lowering and secondary stroke prevention. Am J Cardiol
2003;91:(Suppl G):3-8G.
44. Kawachi I, Colditz GA, Stampfer MJ, Willett WC, Manson JE, Rosner B. Smoking cessation and
decreased risk of stroke in women. JAMA 1993;269:232-6.
45. Jamrozik K, Broadhurst RJ, Anderson CS, Stewart-Wynne EG. The role of lifestyle factors in the etiol-
ogy of stroke: a population-based case-control study in Perth, Western Australia. Stroke 1994;25:51-9.
46. Hankey GJ. Smoking and risk of stroke. J Cardiovasc Risk 1999;5:207-11.
47. Bond R, Rerkasem K, Rothwell PM. Systematic review of the risk of carotid endarterectomy in
relation to the clinical indication for and timing of surgery. Stroke 2003;34:2290-303.
48. Cleveland Clinic Heart Centre. Carotid stenting with codis ANGIOGUARD embolic protection
device equivalent to endarterectomy in high-risk patients. US SAPPHIRE Study: 12-month data.
Available at: www.clevelandclinic.org/heartcenter/pub/news/archive/2003/sapphire9_17.asp.
Accessed 2005 June 2.
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