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Carotid surgery and stenting for stroke prevention Seemant Chaturvedi MD, FAHA, FAAN Professor of Neurology Director, Wayne State University Stroke Program Detroit, MI Schaturv@med.wayne.edu


Patient # 1 ยง Patient is a 60 y.o. woman with L MCA Stroke in ยง ยง ยง

1997 She had severe LICA stenosis with subsequent CEA PMH: Smoking, hyperlipidemia No history of heart disease or COPD


Patient #1 § § § § § § §

RICA has shown progressive stenosis 2006: 50% RICA stenosis 2007: 50-59% 2008: 60-69% 2009: 80-99% Patient has remained asymptomatic Meds include ASA/ER-DP and atorvastatin


Questions ยง ยง ยง ยง

Should she have an angiogram? Should she be referred for CEA? Should she be referred for stenting? Would you continue medical treatment alone?


Case 2 § 84 year old male brought to the ER by family § Family reported that he had two episodes of § § § §

expressive speech difficulty and right facial droop for 10-15 minutes each Hx of HTN, DM On ASA, simvastatin, lisinopril EF 25% MI five years ago, no recent cardiac symptoms


Topics for discussion ยง Observations and guidelines on carotid ยง ยง

endarterectomy (CEA) Recent data on carotid artery stenting (CAS) Consideration of intensive medical therapy


Carotid Revascularization: The times they are a changing?


Absolute Benefits of Carotid Endarterectomy (CEA) 8.5

Absolute RR Ipsilateral Stroke/Yr

9 8 7 6 5

Arr/Yr

4 3 2

1.2

1.3

No Sx

Sx 50-69%

1 0 Sx 70-99%

CEA showed only marginal benefits on annual rates of ipsilateral stroke for patients with asymptomatic or moderate lesions. Dramatic benefit was seen for high-grade symptomatic stenoses.


Annual stroke rates with Carotid Stenosis ยง Symptomatic 70-99% ยง Symptomatic 50-69% ยง Asymptomatic 60-99%

13%/yr 4.4%/yr 2-2.5%/yr


Recommended thresholds for perioperative M&M ยง Symptomatic stenosis ยง Asymptomatic stenosis

<6% <3%


Post-CE Stroke or Death ยง ยง ยง ยง ยง

Ontario Carotid Endarterectomy Registry 6038 patients between 1994-1997 1846 patients were asymptomatic Stroke/death rate of 4.7% in these patients Determination of local complication rate important

Tu JV, et al. Stroke 2003; 34: 2568-2575.


.

Stenosis 70-99% (excluding post-stenotic narrowing) Ipsilateral Carotid Territory Ischaemic Stroke Plus Any Surgical Stroke or Surgical Death

Proportion free of event

1.0 0.9 0.8 0.7 0.6

Log Rank = 30.7 p < 0.00001

0.5 0

1

2

3

4 5 6 7 8 Years from randomisation

Patients Surgery 573 487 454 427 404 374 315 237 157 No surgery 498 393 332 299 284 254 218 166 90

9

10

86 36

20 10 .

Lancet 2003; 361: 107-16


.

Post-Stenotic Narrowing Ipsilateral Carotid Territory Ischaemic Stroke Plus Any Surgical Stroke or Surgical Death Proportion free of event

1.0 0.9 0.8 0.7 0.6

Log Rank = 0.0006 p = 0.98

0.5 0

1

2

3

4 5 6 7 8 Years from randomisation

Patients Surgery 164 148 138 130 121 106 No surgery 122 105 93 92 90 82

90 66

72 47

43 26

9

10

21 11

5 3 .


.

Stenosis 50-69% Any Stroke or Surgical Death

Proportion free of event

1.0 0.9 0.8 0.7 0.6

Log-rank = 9.3 p = 0.002

0.5 0

1

2

3

4 5 6 7 8 Years from randomisation

Patients Surgery 828 694 612 530 437 363 290 194 133 No surgery 721 610 499 421 340 271 206 147 96

9

10

66 48

23 15 .

Lancet 2003; 361: 107-16


Absolute Differences at Five Years Results

P value

70-99%

16.0%

<0.001

50-69%

4.6%

0.04

30-49%

3.2%

0.6

<30%

-2.2%

0.05

Near occlusion

-1.7%

0.9


Factors affecting the risk/benefit ratio Favors medical rx Favors surgery Sex

Female

Male

Lesion

Smooth

Ulcerated

Sx type

Retinal

Hemispheric

Collaterals

Present

Absent

Comorbidity

Present

Absent

Chaturvedi S. Emergency Medicine 2000; 32: 46-55


Effect of carotid endarterectomy stratified by time from last event to randomisation Ipsilateral ischaemic stroke and operative stroke or death

50.0

32.7 70-99%

ARR (%), 95% CI

40.0 30.0

13.8

16.0 9.4

11.2 20.0

50-69%

3.4 0.0

10.0

-2.9

0.0 -10.0 -20.0 0-2

2-4

4-12

12+

Weeks between symptomatic event and randomisation Lancet 2004; 363: 915-24


How many patients need to be operated on? 50-99% stenosis subgroup Men

Number needed to treat (NNT) 9

Women

36

Age <65 years

18

Age >75 years

5

< 2 weeks

5

>12 weeks

125


Assessment: Carotid Endarterectomy? An Evidence-Based Review Report of the Therapeutics and Technology Subcommittee of the American Academy of Neurology S Chaturvedi MD, A Bruno MD, T Feasby MD, R Holloway MD, O Benavente MD, SN Cohen MD, R Cote MD, D Hess MD, J Saver MD, JD Spence MD, B Stern MD, J Wilterdink MD Published in Neurology 2005;65:794-801


Recommendations Use of Carotid Endarterectomy in Symptomatic Patients Stenosis (%)

Recommendation

70-99%

CE is established as effective for recently symptomatic (within previous 6 months) patients with 70-99% ICA angiographic stenosis (Level A).

ยงCE may be considered for patients with 50-69% symptomatic stenosis (Level B) but the clinician should consider additional clinical and angiographic variables (Level C). See tables below.

50-69%

ยงIt is recommended that the patient have at least a five year life expectancy and that the peri-operative stroke/death rate should be <6% for symptomatic patients (Level A).

ยงCE should not be considered for symptomatic patients with <50% <50%

stenosis (Level A). ยงMedical management is preferred to CE for symptomatic patients with <50% stenosis (Level A).


Recommendations Use of Carotid Endarterectomy in Asymptomatic Patients Stenosis Recommendation (%)

60-99%

It is reasonable to consider CE for patients between the ages of 40-75 years and with asymptomatic stenosis of 60-99% if the patient has an expected five year life expectancy and if the surgical stroke or death frequency can be reliably documented to be <3% (Level A). The five year life expectancy is important since peri-operative strokes pose an up front risk to the patient and the benefit from CE emerges only after a number of years.


The Industry View § “Carotid stenting will be the mother of all turf battles” -Former CEO, Boston Scientific


Interpretation of CAS studies ยง Did the study include patients who are good ยง ยง ยง

candidates for CEA (conventional risk) or patients who are high-risk for CEA? Short-term or long-term outcomes reported? Experienced interventionalists or a broad group? Is there a control group?


High risk criteria for CEA


High risk patient ยง Patient is a 70 y.o. woman ยง EF 20% ยง 90% asymptomatic RICA stenosis


Low to medium risk patient ยง 70 year old man ยง Hx of HTN, DM, and CABG five years ago ยง Presents with expressive aphasia and rightยง ยง

sided weakness for 10 minutes Contrast enhanced MRA shows severe LICA stenosis This patient should get CEA


SAPPHIRE


French CEA vs. Stent Study 60-99% symptomatic stenosis (EVA 3S) § CEA § 3.9% Stroke or death at §

30 days 6.1% stroke or death at 6 months

§ Stenting § 9.6% stroke or death at §

N Engl J Med 2006; 355: 1660-71

30 days 11.7 % at 6 months (p=0.02)


What the skeptics are saying § How do we know if this is any better than § §

medical therapy? Will high-risk patients survive long enough to benefit? Many of the events showing benefit of stenting in high-risk patients may have been “troponin leaks” and not clinically significant


Is this a game changer?


Carotid Revascularization Endarterectomy vs Stent Trial (CREST)

§ NASCET-type patients randomized to surgery vs stenting § 2,502 patients § NIH and industry sponsorship (Abbott Vascular) § Primary investigator: Thomas Brott § Clopidogrel preprocedure and postprocedure § Embolism protection device North American Symptomatic Carotid Endarterectomy Trial (NASCET). ACS=Advanced Cardiovascular Systems, Inc. Hobson RW et al, for the CREST Executive Committee. Curr Control Trials Cardiovasc Med. 2001;2:160-164.


CREST eligibility criteria § Symptomatic stenosis either >50% by angio or § § § § §

>70% by ultrasound Asymptomatic stenosis either >60% by angio or >70% by ultrasound Excluded if: Chronic A FIB MI within previous 30 days Unstable angina


CREST baseline characteristics


CREST main results CEA

CAS

P value

Stroke, 6.8% death, MI, + ipsilateral stroke after 30 days Stroke within 2.3% 30 days

7.2%

0.51

4.1%

0.01

MI within 30 days

1.1%

0.03

2.3%


Questions following CREST ยง How significant are the MI events noted in the ยง ยง ยง ยง

periprocedural period? Without the MIs, CEA was better than CAS for symptomatic patients Should clinicians consider the observations on age? Can the CAS results be replicated in the real world? How will regulatory agencies view the recent studies?


Carotid stenting 2010 Acceptable risk for High risk for CEA CEA

Symptomatic 70-99%

CEA

Consider stenting

Asymptomatic

Medical therapy or Evaluate life CEA expectancy, medical rx preferred, or stenting study


What about intensive medical therapy?

ยง There has never been a large multi-center study

ยง ยง ยง

done to compare carotid revascularization + intensive medical therapy vs. intensive medical therapy alone LDL <70 mg/dl SBP <140 for nondiabetics, <130 for diabetics Similar to SAMMPRIS, except for extracranial stenosis


Carotid stenosis 2010 Medical Management § § § § § § §

Newer antiplatelet agents Aggressive use of statins Targeted BP lowering ACE/ARB utilization Smoking cessation Control of other risk factors (DM) Other lifestyle interventions


Conclusions ยง CEA is a proven treatment and is more effective ยง ยง ยง ยง

for symptomatic stenosis than for asymptomatic stenosis CAS is approved for select patients deemed at high risk for CEA Results of CREST and other studies will be evaluated by regulatory authorities ? Broader approval for CAS Medical therapy has improved and will likely reduce the need for carotid revascularization


Chaturvedi-Carotid-Surgery-&-Stenting-for-Stroke-Prevention  

Carotid surgery and stenting for stroke prevention Seemant Chaturvedi MD, FAHA, FAAN Professor of Neurology Director, Wayne State University...