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Stroke prevention a reality in this millennium
1. STROKE PREVENTION- A REALITY
IN THIS MILLENNIUM
Prof. A.V. SRINIVASAN,
MD, DM, Ph.D, F.A.A.N, F.I.A.N.
Emeritus Professor
The Tamilnadu Dr. M.G.R. Medical University
Former Head
Institute of Neurology, Madras Medical College
21-08-10
2. Cerebrovascular
Prevention
Is survival a mere stroke of Luck?
âMy Opinions are founded on knowledge but modified by experienceâ
3. INTRODUCTION
ď Perceptual Sense(Observation)
ď Word Sense (Recording)
ď Common Sense (Thinking)
ďŹ Will lead you to get - Clinical Sense
â He who cannot forgive others destroys the bridge over
which he himself must passâ - Annoy
4. Cerebrovascular disease â
Mind boggling facts
ď§ World wide incidence: 2/1000 population/annum 1
ď§ Incidence in people aged 45 â 84 years: about 4/1000 1
ď§ Incidence in India: was 36/100,000 for the year 1998-1999 3 in a
study in Calcutta
ď§ Incidence of mortality due to stroke (India: WHO study):
73/100,000 per year2
CVD is the most disabling of all neurologic diseases.
50% of survivors have a residual neurologic deficit.
Greater than 25% require chronic care.
1.A practical approach to management of stroke patients; 1996; 360-384
2. Epidemology of cerebrovascular disorders in India; 1999; 4-19
3. Neuroepidemiology 2001;20:201-207
If you think you can or you canât You are always right
5. Annual risk CVD, MI, vascular death
following TIA, minor CVD
⢠CVD 6.7 %
⢠MI 2.5 %
⢠Death 7.2 %
⢠CVD, MI, Vascular death 8.6 %
⢠CVD, MI, Death 10.3 %
Experience can be defined as yesterdayâs answer to
todayâs problems
6. Common Stroke Mimics
ď§ Hypoglycemia
ď§ Post ictal state
ď§ Drug overdose
ď§ Concussion with neck injury
ď§ Migrainous accompaniment
ď§ Encephalopathies with focal signs
ď§ Hyponatremia
ď§ Subdural hematoma, Empyema
ď§ Focal Encephalitis: Herpes
Being ignorant is not so much a shame as being unwilling to learn
7. Drugs used for stroke
preventionâŚ
ACE inhibitors
Lipid lowering agent
Anti-platelets
9. Why ACE inhibitors in stroke
prevention ?
ď Blood pressure lowering effect
ď Prevention of endothelial dysfunction
ď Prevention of progression of
atherosclerosis
ď Favourable alteration of the fibrinolytic
balance
ď Prevention of cardiac remodelling
Clinical evidenceâŚ
10. Objective of PROGRESS
Whether in patients withâŚ
Stroke OR TIA
Perindopril + Indapamide
Risk of stroke & vascular events
WHO â ISH initiated the study
PROGRESS collaborative group. Lancet 2001;358:1033-41.
11. Patient selection criteria
Evidence of
Stroke / TIA
> 2 weeks and < 5 years of event
âŚbut without a definite indication /
contraindication to treatment with an ACE inhibitor
PROGRESS collaborative group. Lancet 2001;358:1033-41.
12. Patient selection criteria
Young
Diabetic Non-diabetic
Included
Hypertensive Normotensive
Old
PROGRESS collaborative group. Lancet 2001;358:1033-41.
13. Baseline characteristics
Characteristic Perindopril + indapamide Placebo
N = 3051 N = 3054
Mean age (yrs) 64 64
Females (%) 30 30
Stroke history
ďś Ischaemic stroke (%) 71 71
ďś Haemorrhagic stroke (%) 11 11
ďś TIA (%) 22 22
ďś Duration since event (months) 8 8
Diabetes (%) 13 12
CAD (%) 16 16
Mean BP (mmHg) 147/86 147/86
Hypertension (%) 48 48
Antihypertensive therapy (%) 50 51
PROGRESS collaborative group. Lancet 2001;358:1033-41.
14. Total stroke
28%
28%
Placebo group
risk
risk
reduction
Risk reduction (%)
reduction
38%
Active group
0 1 2 3 4 Years
PROGRESS collaborative group. Lancet 2001;358:1033-41.
18. Treatment acceptability
Active group
Causes of withdrawal (%)
Placebo
23
21
8 8
2 2 0.9
0.4
All causes Voluntary Cough Hypotension
PROGRESS collaborative group. Lancet 2001;358:1033-41.
19. PROGRESS results showedâŚ
ď Perindopril+ indapamide substantially
reduced risk of secondary stroke and
other vascular events
Irrespective of
ďŹ
Age
ďŹ Blood pressure level
ďŹ Other diseases
ďŹ
Background medication
PROGRESS collaborative group. Lancet 2001;358:1033-41.
20. SummariseâŚ
ď ACE inhibitors are beneficial in the
prevention of stroke
ď All stroke patients, hypertensive as well as
normotensives should receive an ACE
inhibitor
ď All CAD patients, diabetic patients, who
are at-risk of developing stroke should
receive an ACE inhibitor
Which ACE inhibitor ?
21. Which ACE inhibitor ?
Treatment Number-needed-to-treat
Perindopril- 23 to prevent
based therapy 1 stroke in 5 years
Ramipril-based 67 to prevent
therapy 1 stroke in 5 years
JNC â 7 reference only to perindopril
Stroke 2002;33:862-875. JNC-7, JAMA May 2003 â Vol.289; No.19: 2560-2571.
23. Primary Prevention of Ischemic Stroke
A Guideline From the American Heart
Association/American Stroke
Association Stroke Council
ď It is recommended that patients with
known CAD and high-risk hypertensive
patients even with normal LDL cholesterol
levels be treated with lifestyle measures
and a statin (Class I, Level of Evidence A).
Stroke 2006;37;1583-1633
24. JUPITER & STROKE
ď JUPITER is the first large-scale, prospective
study to examine the role of statin therapy in
individuals with low to normal LDL-C levels, but
with increased cardiovascular risk identified by
elevated CRP
ď Nearly half of all cardiovascular events occur in
patients who are apparently healthy and who
have low or normal levels of LDL-C
ď hsCRP predicts cardiovascular disease
independent of LDL-C levels
25. JUPITER JUPITER
Trial Design
Multi-National Randomized Double Blind Placebo Controlled
Trial of
Rosuvastatin in the Prevention of Cardiovascular Events
Among Individuals With Low LDL and Elevated hsCRP
Rosuvastatin 20 mg (N=8901)
No Prior CVD or DM
Men >50, Women >60
LDL <130 mg/dL 4-week Placebo (N=8901)
hsCRP >2 mg/L run-in
Argentina, Belgium, Brazil, Bulgaria, Canada, Chile, Colombia, Costa Rica,
Denmark, El Salvador, Estonia, Germany, Israel, Mexico, Netherlands,
Norway, Panama, Poland, Romania, Russia, South Africa, Switzerland,
United Kingdom, Uruguay, United States, Venezuela
Ridker et al, Circulation 2003;108:2292-2297.
26. JUPITER: Results
No. of patients with any stroke
70 64
60
48%
50 Reduction
40 33 *
30
20
10
0
Rosuvastatin Placebo
n=8901 n=8901
Circulation 2010;121:143-150
* p< 0.002 vs. placebo
32. A meta-analysis of WOSCOPS+AFCAPS/TexCAPS+MEGA
â˘Stroke reduction by 14% (statistically non-
significant)
A meta-analysis of these 3 trials along with JUPITER
â˘Stroke reduction by 25% (statistically
significant)
Analysis of JUPITER only:
Stroke reduction by 48% (statistically non-significant)
33. Summary
ď Stroke is one of the leading cause of
death worldwide.
ď Guidelines recommends the use of statins
for primary as well as secondary
prevention of stroke.
ď JUPITER trial has established that
rosuvastatin is the most effective statin in
preventing stroke in high risk population.
34. Symptomatic Carotid
Endarterectomy ASA 2006
Secondary Stroke Recs
⢠Ipsilateral severe (70% to 99%) carotid stenosis,
CEA is recommended (Class I, Evidence A).
⢠Ipsilateral moderate (50% to 69%) carotid stenosis,
CEA is recommended depending on age, gender,
comorbidities, and the severity of symptoms (Class I,
Evidence A).
⢠Stenosis <50%, there is no indication for CEA (Class
III, Evidence A).
35. Urgent Endarterectomy
Surgery within 2 weeks is suggested rather than delaying surgery
(Class IIa, Evidence B).
Rothwell PM. Lancet 2004;363(9413):915-24
36. Carotid Angioplasty and Stenting
ASA 2006 Secondary Stroke
Recs
⢠CAS may be considered (Class IIb, Evidence B).
- Stenosis (>70%) difficult to access surgically
- Medical conditions that greatly increase the
risk for surgery, or
- When other circumstances exist such as
radiation-induced stenosis or restenosis after
CEA.
⢠CAS is reasonable when performed by operators
with morbidity and mortality rates of 4% to
6% (Class IIa, Evidence B).
37. Atrial Fibrillation
ASA 2006 Recommendations
⢠For patients with ischemic stroke or TIA with
persistent or paroxysmal (intermittent) AF,
anticoagulation with adjusted-dose warfarin (target INR
2.5, range 2.0 to 3.0) is recommended (Class I,
Evidence A).
⢠For patients unable to take oral anticoagulants,
aspirin 325 mg per day is recommended (Class I,
Evidence A).
38. Stroke Prevention:
Non-cardioembolic
ASA 2006 Recommendations
For patients with noncardioembolic ischemic
stroke or TIA, antiplatelet agents are
recommended rather than oral anticoagulation to
reduce the risk of recurrent stroke and other
cardiovascular events (Class I, Evidence A).
39. Stroke Prevention: Non-
cardioembolic
ASA 2006 Recommendations
⢠Acceptable options for initial therapy
(Class IIa, Evidence A).
- aspirin (50-325 mg qd)
- the combination of aspirin and extended-
release dipyridamole (25/200 mg bid)
- clopidogrel (75 mg qd)
40. Antiplatelet Therapy
ASA 2006 Recommendations
⢠Compared to aspirin alone, both the combination of
aspirin and extended-release dipyridamole and
clopidogrel are safe.
⢠The combination of aspirin and extended-release
dipyridamole is suggested instead of aspirin alone
(Class IIa, Level A).
⢠Clopidogrel is suggested instead of aspirin alone
based on direct comparison trials
(Class IIb, Level B).
41. Secondary Stroke Prevention
ASA 2006 Recommendations
⢠Insufficient data are available to make evidence-
based recommendations regarding choices between
antiplatelet options other than aspirin. Selection of an
antiplatelet agent should be individualized based on
patient risk factor profiles, tolerance, and other clinical
characteristics.
42. Secondary Stroke Prevention
ASA 2006 Recommendations
⢠The addition of aspirin to clopidogrel increases
the risk of hemorrhage and is not routinely
recommended for stroke or TIA patients (Class
III, Evidence A).
⢠For patients allergic to aspirin, clopidogrel is
recommended (Class IIa, Evidence B).
43. MATCH: Safety Outcomes
⢠Excess life-threatening bleeding events with
combination versus clopidogrel monotherapy:
96 (2.6%) vs. 49 (1.3%); p<0.0001
⢠Excess minor bleeds with combination therapy
versus clopidogrel alone:
120 (3.2%) vs. 39 (1.0%); p<0.0001
Diener H-C et al. Lancet 2004;364:331-7
44. Secondary Stroke Prevention
ASA 2006 Recommendations
⢠For patients who have an ischemic
cerebrovascular event while taking aspirin,
there is no reliable evidence that increasing the
dose of aspirin provides additional benefit.
Although alternative antiplatelet agents are
often considered for these patients, no single
agent or combination has been specifically
evaluated in patients who have had an event
while receiving aspirin.
45. Stroke and Pregnancy
ASA 2006 Secondary Stroke Recs
⢠High-risk thromboembolic conditions consider:
- adjusted-dose UFH throughout pregnancy,
- adjusted-dose LMWH with Factor Xa monitoring
- UFH or LMWH until week 13, followed by
warfarin until mid-3rd trimester, then UFH or
LMWH in last trimester (Class IIb, Evidence
C).
⢠Lower risk conditions
- UFH or LMWH in the first trimester followed
by - low-dose aspirin for the remainder of the
pregnancy (Class IIb, Evidence C).
46. Postmenopausal Hormones
ASA 2006 Secondary Stroke Recs
For women with ischemic stroke or TIA,
postmenopausal hormone therapy (with estrogen
with or without a progestin) is not recommended
(Class III, Evidence A).
47. Womenâs Health Initiative
⢠16,608 postmenopausal women, 50-79 years,
with an intact uterus at baseline were recruited
by 40 U.S. clinical centers for the period 1993-
1998.
⢠Received conjugated equine estrogens, 0.625
mg/d, plus medroxyprogesterone acetate, 2.5
mg/d, in 1 tablet (n = 8506) or placebo (n = 8102).
⢠After a mean of 5.2 years of follow-up, the trial
was stopped because of high rates of invasive
breast cancer and the global index statistic
supported risks exceeding benefits.
Rossouw et al. JAMA 2002;288(3):321-33
48. Other Circumstances
ASA 2006 Secondary Stroke Recs
⢠Dissections
⢠PFO and hyperhomocysteinemia
⢠Hypercoagulable states
⢠Sickle cell disease
⢠Cerebral venous thrombosis
⢠Anticoagulation after cerebral hemorrhage
49. Level A Recommendations
⢠Antihypertensive treatment
⢠Glucose control to reduce microvascular
complications of diabetes
⢠Statins to reduce LDL to <100 or <70 for high-risk
patients (sympt CHD or athero)
⢠CEA for sympt 50-99%
⢠NO CEA for <50% sympt stenosis
⢠Warfarin at INR 2.5 for Afib. (ASA if unable)
⢠Antiplatelet for noncardioembolic
⢠NO combination clopidogrel and ASA
50. Carotid Angioplasty and Stenting
ASA 2006 Secondary Stroke Recs
⢠CAS may be considered (Class IIb, Evidence B).
- Stenosis (>70%) difficult to access surgically
- Medical conditions that greatly increase the
risk for surgery, or
- When other circumstances exist such as
radiation-induced stenosis or restenosis after
CEA.
⢠CAS is reasonable when performed by operators
with morbidity and mortality rates of 4% to
6% (Class IIa, Evidence B).
51. Other Circumstances
ASA 2006 Secondary Stroke Recs
⢠Dissections
⢠PFO and hyperhomocysteinemia
⢠Hypercoagulable states
⢠Sickle cell disease
⢠Cerebral venous thrombosis
⢠Anticoagulation after cerebral hemorrhage
52. Level A Recommendations
⢠Antihypertensive treatment
⢠Glucose control to reduce microvascular
complications of diabetes
⢠Statins to reduce LDL to <100 or <70 for high-risk
patients (sympt CHD or athero)
⢠CEA for sympt 50-99%
⢠NO CEA for <50% sympt stenosis
⢠Warfarin at INR 2.5 for Afib. (ASA if unable)
⢠Antiplatelet for noncardioembolic
⢠NO combination clopidogrel and ASA
53. PROGNOSTIC PEARLS
ď§ Flaccid Paralysis for more than 96 hrs
ď§ When tendon reflexes recover without return of voluntary
movement â prognosis poor
ď§ Recovery of sensory less in usual to a degree. Postion
sense recovers but not pain and temperature
ď§ Recovery from Dysphasia is never complete
ď§ Dysarthria usual improves and Dysphagia never improves
ď§ Diplopia due to brain stem is usually permanent
ď§ Conjugate gaze â recovers
ď§ Vertigo improves but hearing loss is permanent
ď§ Pseudobulbar palsy permanent
âByNature All Men/W en are alike but
om
byEducation widelydifferentâ
54. CVD â Prevention or Cure?
While number of curative methods are
available, preventive therapy is
undoubtedly the main strategy in the
management of CVD
Lijec Vjesn. 2003 Nov-Dec;125(11-12):322-8
The sign wasnât placed there
By the Big Printer in the sky
57. READ not to contradict or confute
Nor to Believe and Take for Granted
but TO WEIGH AND CONSIDER
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Today, anti-platelets, lipid lowering agents and ACE inhibitors are being used for stroke prevention. Anti-platelets and lipid lowering certainly play an important role. Today, I will restrict my talk on ACE inhibitors in stroke prevention.
But why ACE inhibitors⌠ACE inhibitors, in addition to their blood pressure lowering effect also have some additional properties which could contribute to stroke prevention. LikeâŚ(please read the slide). What is the clinical evidence ?
PROGRESS sought to determine whether in patients with a history of stroke or TIA, treatment with perindopril + indapamide reduced the risk of recurrent stroke and major vascular events. This study was initiated by WHO-ISH and patients were recruited from 10 countries across the world.
To be selected patients had to have evidence of a stroke or TIA after 2 weeks but within 5 years of the acute event. Thus, all patients had a history of stroke. Additionally, the patients had to have no definite indication (such as heart failure) or contraindication (such as previous intolerance) to an ACE inhibitor. Patients selected wereâŚ
⌠hypertension under treatment (excluding ACE inhibitor), normotensive patients or those with other disease such as diabetes were also included in the study. PROGRESS therefore studied a broad range of associated disease that may occur with a history of stroke, as would be seen in daily practice. Importantly patients were treated with perindopril/control over and above other antihypertensive treatment.
As was expected, because of the randomisation, both groups were balanced at baseline. About 50% had hypertension and received antihypertensive therapy, which means that no patient was left without antihypertensives if required. What was the effect of treatment on total stroke, the primary outcome?
The effects of treatment started to appear within one year, and progressively fewer strokes occurred in the treatment group compared to placebo. Overall, after about 4 years the stroke risk reduction in the active group was 28% with a confidence interval of 17-38%. The results on stroke subtypes were similar.
The results on fatal/disabling stroke were significantly higher at 33% risk reduction and this was also manifested for non-fatal stroke by a risk reduction of 24%.
Treatment with perindopril + indapamide reduced ischaemic stroke risk by one quarter, and haemorrhage stroke risk by one half.
Risk reduction in stroke was seen in normotensive as well as in hypertensives.
Total withdrawal rate was nearly the same with treatment as with placebo. Of the major causes of withdrawal, cough was just 2% and hypotension which is a major concern in post stroke treatment was infrequent. Thus perindopril based treatment is acceptable for the long-term prevention of secondary stroke. ⌠was the treatment easy to comply with ? Like the EUROPA trial the treatment acceptability is good even in the PROGRESS trial.
Please read the slide.
Please read the slide.
If we take into consideration the recent review published in the journal Stroke, the NNT with perindopril is only 23 vs. 67 with ramipril. Thus perindopril appears to be a more powerful treatment in secondary stroke prevention. Even the latest JNC-7 refers only to the PROGRESS trial with perindopril for stroke prevention. Given the significant public health impact of stroke, it is certainly advisable to consider these preventive measures for all patients.
high-sensitivity C-reactive protein, an inflammatory biomarker, independently predicts future vascular events. JUPITER trial was done in subjects with no prior cardiovascular disease or diabetes, LDL <130 mg/dL, and hsCRP level of 2 more than 2 mg/dL. Subjects were randomized to rosuvastatin 20mg daily or matching placebo. Follow up was done up to 60 months after randomization. The primary outcome was the occurrence of a first major cardiovascular event, defined as nonfatal myocardial infarction, nonfatal stroke, hospitalization for unstable angina, an arterial revascularization procedure, or confirmed death from cardiovascular causes. Secondary end points included the components of the primary end point considered individually â arterial revascularization or hospitalization for unstable angina, myocardial infarction, stroke, or death from cardiovascular causes â and death from any cause.
All of these guidelines must be taken in context of the surgeon performing the procedure. The benefits seen with symptomatic carotid endarterectomies only outweigh the risks involved when the surgeon performing the procedure has a 6% or less morbidity/mortality rate. This low complication rate has been proven to be associated with surgeons in high-volume centers. 1, 2 Age >75 should not be an exclusion for endarterectomy. In fact, some studies suggest they may benefit more than younger patients. 3 1 North American Symptomatic Carotid Endarterectomy Trial Collaborators (NASCET). Beneficial effect of carotid endarterectomy in symptomatic patients with high-grade carotid stenosis. N Engl J Med. 1991; 325:445-53. 2 Cina, et al. Cochrane Database Review, 2000 3 Alamowitch, et al. Lancet, 2001
Data from Rothwell, et al, found that the highest risk period after stroke is within the first 2 weeks, and that the event rate declined over time. The figure above demonstrates the absolute risk reduction with surgery, and the different color bars represent critical and high-grade stenoses. The confidence intervals begin to cross 0 at 2-4 weeks for high-grade, and >12 weeks for critical carotid stenoses. This has led to the recommendation that symptomatic, ipsilateral carotid endarterectomy be performed within 2 weeks of the initial event, instead of the previous tendency for a âcooling offâ period. Rothwell, et al, Lancet 2004
The direct comparison between carotid endarterectomy and carotid stenting is being studied in the ongoing CREST trial, funded by the NIH. Previous studies have had smaller numbers, included inexperienced operators, or did not include distal protection which is usually considered standard practice currently. The SAPPHIRE trial randomized 334 patients to endarterectomy or stenting (with distal protection), and found that stenting was not inferior to endarterectomy, and in fact had lower event rates in the stenting arm. Most of this suggestion of benefit was a lower risk of myocardial infarction in high-risk patients. More definitive data is needed before recommendation of widespread stenting of extracranial carotid disease. Yadav, et al, NEJM 2004.
Atrial fibrillation (whether persistent or paroxysmal) is recognized as a potent risk factor for recurrent stroke and the data is strong that supports the use of warfarin to reduce this risk. Multiple clinical trials 1,2,3 , including the European Atrial Fibrillation trial 2 , support this recommendation. Only patients unable to tolerate oral anticoagulants should be administered aspirin for prevention, due to the clear superiority of warfarin in these patients. 2,3 1 Hylek EM et al. N Engl J Med 1996;335:540-546 2 EAFT Study Group. Lancet 1993;342:1255-1262 3 SPAF III investigators. Lancet 1996;348:633-638
Since the 1999 guidelines, there has been increasing evidence to support the fact that NONCARDIOEMBOLIC ischemic strokes should receive antiplatelet agents, not oral anticoagulants, for secondary stroke prevention. This recommendation is supported by the WARSS 1 and WASID 2 studies, in which aspirin was compared to warfarin and aspirin was safer with equal risk reduction. 1 Mohr JP et al. N Engl J Med 2001;245:1444-1451 2 Chimowitz MLM et al. Stroke 2004;35:235
Although stroke experts may disagree on which specific antiplatelet agent to use in a given patient, all agree on the importance of antiplatelet therapy in patients with noncardioembolic ischemic stroke. Based on the results of multiple clinical trials, all of the agents listed above are considered acceptable first line options. Since direct head-to-head comparisons demonstrating equivalence DO NOT exist, this is a Class IIa recommendation.
Statements regarding the choice between antiplatelet agents is more controversial. Although all can agree on the safety of the three agents, the combination of aspirin and extended-release dipyridamole is suggested over aspirin alone, based primarily on the results of ESPS2 1 . It is a Class IIa recommendation because other trials of dipyridamole alone were negative. It is considered Level A because of other positive trials of the combination. 2 The suggestion to use clopidogrel over aspirin is based on the CAPRIE study. 3 It is considered Class IIb because the effect was NOT significant in the patients included because of prior stroke. It is Level B because it is based on a single trial. The use of ticlopidine is no longer recommended due to its side effect profile (excessive diarrhea and blood dyscrasias) and failure to provide significant benefit. In addition, a recent study in African Americans, showed no benefit over aspirin alone (AAAPS)4. 1 Diener HC et al. J Neurosci 1996;143:1-13 2 ESPS. Lancet 1987;2:1351-1354 3 CAPRIE Steering Committee. Lancet 1996;384:1329-1339 4 Gorelick PB et al. JAMA 2003; 289:2947-2957
Additional recommendations regarding antiplatelet recommendations include a strong recommendation against the use of the combination of clopidogrel and aspirin in patients with stroke or TIA, based on the lack of additional benefit over clopidogrel alone but an excess bleeding risk. This is based on the results of the MATCH trial. 1 The only time these agents should be used together in stroke patients is when the patient has had a myocardial event within the past 9-12 months, based on the CURE study. 2 For patients allergic to aspirin, clopidogrel is recommended based on the CAPRIE study. 3 1 Diener HC et al. Lancet 2004;364:331-337 2 Yusuf S et al. N Engl J Med 2001;345:494-502 3 CAPRIE Steering Committee. Lancet 1996;348:1329-1339
Bleeding events were significantly increased in patients receiving aspirin / clopidogrel combination therapy.
Examples of high-risk conditions include known coagulopathies or prosthetic heart valves.
Rossouw, et al, JAMA 2002
All of the strongest recommendations are listed above, both Class I and Class III, with level A evidence (multiple clinical trials).
The direct comparison between carotid endarterectomy and carotid stenting is being studied in the ongoing CREST trial, funded by the NIH. Previous studies have had smaller numbers, included inexperienced operators, or did not include distal protection which is usually considered standard practice currently. The SAPPHIRE trial randomized 334 patients to endarterectomy or stenting (with distal protection), and found that stenting was not inferior to endarterectomy, and in fact had lower event rates in the stenting arm. Most of this suggestion of benefit was a lower risk of myocardial infarction in high-risk patients. More definitive data is needed before recommendation of widespread stenting of extracranial carotid disease. Yadav, et al, NEJM 2004.
All of the strongest recommendations are listed above, both Class I and Class III, with level A evidence (multiple clinical trials).