STROKE AND TIA - OPTIMAL SURGICAL MANAGEMENT OF SYMPTOMATIC CAROTID DISEASEMr. Patrick Chong Consultant Vascular & Endovascular Surgeon

Surrey Heart, Stroke and Vascular CentreFrimley Health NHS Foundation TrustGuildford November

2014

Stroke – the figures

3rd leading cause of death and

120 000 new strokes annually500 000 new strokes annually

3 times as many women die from stroke as from breast cancer.

Stroke – the costs$51 billion - Stroke related treatment

costs and disability payments in 2003

£7 billion – Stroke related treatment costs and disability payments in 2005

Treatment and research under funded in the UK?£2 million per annum in the UK

c.f. Cancer £120 million and Heart Disease £43 million

Rothwell 2001 Lancet

The dangers of stroke

1 in 4 men before 85 years old1 in 5 women before 85 years old

30% of stroke patients die within 30 days

Up to 32% will have a recurrent stroke within 30 days1 in 4 stroke patients have a recurrent stroke

Brain Attack!

Vladimir C. Hachinski MD Canadian Neurologist

r-TPA currently the only FDA approved treatment for acute stroke to be givenwithin 4.5 HOURS of the start of symptoms.

The majority of patients don't report to the emergency room until more than 24 hours after the onset of stroke symptoms

52 % of acute stroke patients unaware they were experiencing a stroke.

Current organisation of care in UKNational Sentinel Audit

2004 2006 2010Stroke units 71% 91% 83%Thrombolysis offered 18% 50%Neurovascular clinics 65% 78% 98%

Rapid transfer protocols 4% 12% 22%

High risk patients seen < 7 days 35% 43%

TIA clinic median waiting (days) 14 12 3 1 FPH

Current emergency care in UKNational Sentinel Audit 2006 vs. 2010 vs. 2014

Access to brain imaging < 12 hours 48% vs. 87%

Access to brain imaging < 24 hours 95% vs. 99%

Thrombolysis offered to eligible pts 18% vs. 50% vs. 80%

WHAT HAS CHANGED?

Stroke Telemedicine

Ambulance Services Pre-alerts

24 imaging and reporting for CT / CT in ED

ED led thrombolysis

“There is more to stroke prevention than CEA” – AR Naylor 2007

Risk factors for stroke

Modifiable Hypertension Smoking Hyperlipidaemia High grade carotid stenosis Atrial Fibrillation Diabetes Controversial e.g. OCP, Obesity, Alcohol Non-modifiable Age Male sex Ethnicity

Fate of symptomatic carotid disease Stroke incidence

1 Year 5 years

Previous Symptoms

TIA 12-13% 30-35%Stroke 5-9% 25-45%

Norris JW et al. Stroke 1991

Fate of asymptomatic carotid disease 1 Year

< 75% ICA stenosis 1.5% Stroke

> 75% ICA stenosis 3.3% Stroke

7.5% TIA

Norris JW et al. Stroke 1991

Does plaque morphology matter?Risk of stroke in symptomatic patients

95% stenosis 21% Non-ulcerated plaque

95% stenosis 73%Ulcerated plaque NASCET study 1991

Does symptomatic carotid stenosis matter?

Which patients should be treated first? 4799 patients tested using ABCD (2) score

2-day risk of stroke

Score of 0 – 3 (1012 patients) 1%Score of 4 – 5 (2169 patients) 4.1%Score of 6 – 7 (1628 patients) 8.1%

Johnston SC, Rothwell PM, Nguyen-Huynh MN, et al. Validation and refinement of scores to predict very early stroke risk after transient ischaemic attack. Lancet 2007

Carotid Endarterectomy (CEA)

The earliest reportLoucks et al. 1936Union Medical College, Beijing, China.

Young male with recurrent TIAsRight hemiplegia and aphasiaExcision of ICA occlusionPatient recovered

Archives of Surgery 1938

Speed is of the essence!

First carotid endarterectomy1953De Bakey JAMA 1975

Reconstruction of internal carotid artery in a patient with intermittent attacks of hemiplegia Eastcott, Pickering and Rob Lancet 1954

The evolution of carotid surgery

Reported 1955

Reported 1975

Reported 1954

Pre-CEA imaging – current UK Duplex only 65%

Duplex and MRA 13% Duplex and arch angiogram 9% Duplex and CTA 6% MRA only 2% CTA only 2% Arch angiogram only

2%

GALA trial preliminary dataGough et al. 2007Leeds

Mofidi et al. 2006

To patch or not to patch?GALA Trial (current UK practice)

Always 75%Selective 20%Never 5%

“Patch angioplasty versus primary closure for CEA”Bond et al. 2003Cochrane Database of Systematic Reviews

Outcome no different for different patch types

Significant reductionsStrokeDeathEarly ThrombosisLate Restenosis

Intra-operative cerebral perfusionNever shunt 5%

Speed

Shunt all patients 70%Mainly GA patients

Selectively shunt 25%Stump pressures 25%EEG 5%TCD 35%Awake patient – regional cervical block

“Routine or selective carotid artery shunting for CEA”Bond et al. 2001Cochrane Database of Systematic ReviewsNo evidence to support a policy of routine, selective or no shunting

How does surgery compare with best medical therapy in symptomatic carotid disease?

PrimaryPrimary

EndpointEndpoint

TrialTrial NN StenosisStenosis

(%)(%)MedicalMedical

(%)(%)SurgicalSurgical

(%)(%)P P

valuevalueARRARR

(%)(%)NNTNNT

NASCETNASCET

19911991659659 >70>70 32.332.3 15.815.8 <0.00<0.00

1111.311.3 99

ECSTECST

1991199130083008 >70>70 21.921.9 12.312.3 <0.00<0.00

111.51.5 6868

VASSTVASST

19911991189189 >50>50 19.419.4 7.77.7 0.010.01 17.217.2 66

Surgery versus Stenting outcomesCAVATAS

2001

LEXINGTON 1

2001SAPPHIRE

2004

EVA-3S

2006

SPACE

2006

ICSS

2010

CREST

2010

CEA / CAS CEA / CAS CEA / CAS

71%

No

Symptoms

CEA / CAS CEA / CAS CEA / CAS CEA / CAS

Number

randomised

253 / 251 53 / 51 151 / 156 262 / 265 595 / 605 855 / 858 1251 / 1271

Cranial nerve

8.7% / 0% 8.0 % / NS 5.3% / 0% 7.7% / 1.1% NS / NS 5.3% / 0.1% 4.7% / 0.3%

Wound 6.7%/ 1.2 % 8.0% / 0 % 10.6% / 8.3%

1.2% / 3.1% NS / NS 5.8% / 3.6% 0.2% / 1.6%

Stroke 9.9% / 10% 0% / 0% 20 % / 12% / 9.6% 7.4 % / 6.8% 4.1% / 7.5% 2.3 %/ 4.1%

Death 2 % / 3 % 1.9% / 0 % Combined 6%

1.2% / 0.8% 0.9% / 0.7% 0.8% / 2.2% 0.3% / 0.7%

Combined

Death

Any Stroke

5.9% / 6.4% 1.9% / 0% 6.1 % / 5.8%

For AS patients

3.9% / 9.6% 6.5% / 7.7% 5.2% / 8.5% 3.2% / 6.0%

What would you rather choose?

Are you sure you still want a stent?

Carotid endarterectomy outcomes

N=159N=159

2007-20102007-2010*N=2236*N=2236

2007 J Vas 2007 J Vas SurgSurg

*N=5513*N=5513

20082008

30-day Stroke / 30-day Stroke / TIA (%)TIA (%)

3.1% (n=5)3.1% (n=5) 1.4%1.4% 1.8%1.8%

30-day MI (%)30-day MI (%) 2.5% (n=4)2.5% (n=4) 0.5%0.5% 0.8%0.8%

30-day Death 30-day Death (%)(%)

3.1% (n=5)3.1% (n=5) 0.6%0.6% 0.5%0.5%

Cranial Nerve Cranial Nerve Injuries (%)Injuries (%)

2.1% (n=2)2.1% (n=2) 0.4%0.4% 4.5%4.5%

Return to Return to theatrestheatres

0.6% (n=1) NSNS 2.1%2.1%

Median length Median length of stay (days)of stay (days)

33 4.34.3 33Asymptomatic patients 8.8% FPH 64% MGH16% NVD

Institution No. of Procedures

PatientsDischargedWithout stroke / death in 30 days

Adjusted rate of stroke / death %

Days from symptom to surgery Median (IQR)

Length of stay (days)Median (IQR)

FPH 211 207 2.0 8 (5,12)

2 (1,5)

National

2.5 12

Vascular Services Quality Improvement Programme (VSQIP)November 2014

Surgeon outcomes for carotid endarterectomy

Dates 1st October 2010 to 30th September 2013

Rationale for delaying CEA Risks of haemorrhagic transformation

infarctwith early surgery in acute stroke

Delay of 4-6 weeks recommended

Wylie (1964)Thompson (1970)DeWeese (1971)Torgovnick (2007)

When should surgery be offered?Risk of stroke andtiming of carotid endarterectomy

DOES TIMING OF SURGERY MATTER?Carotid Endarterectomy Trialists Collaboration (CETC)

Number of ipsilateral strokes prevented at five years by performing 1000 CEAs in symptomatic patients with 50-99% stenoses relative to days from last symptom to surgery (based on reanalysis of CETC data) Rothwell Lancet 2004

Faster surgery for females

“Benefit from CEA in women was apparent in those randomized within 2 weeks of their last symptomatic ischemic event”

“Current guidelines in Europe and the USA which state only that CEA should be performed within 6 months of last symptoms should be amended in the light of these results.”

Rothwell PM et al. Stroke 2004; 35: 2855-2861.

Delays! Delays! Delays!

Median time to surgery Days

UK national carotid audit 1997 189Newcastle audit 1995 120Oxford audit 2005 100 GALA trial 2008 82Frimley Park Hospital 2007-08 67Frimley Park Hospital 2010-2014

8

University of Calgary experience Stroke 2006

12% admitted patients required surgery 72% operated within 2 weeks in 2002 92% operated within 2 weeks in 2004

37% operated within 2 weeks on NVD 14% operated within 2 weeks at Frimley in 2010 100% operated within 2 weeks at Frimley in 2014

43 consecutive patients 12 months prior to NICE stroke guidelines (July 2008)

All TIA or non-disabling stroke

94% patients scored ABCD2 > 4 (high risk) Mean time to consultant vascular opinion 28 days 81% patients had carotid duplex within 7 days 32% of high risk patients had CT scan within 24

hours 14% of patients had surgery within 2 weeksASIT Conference Nottingham March 2009

Conclusions (in 2008)

WE WERE NOT FAST ENOUGH!

Significant delays existed in our local urgent carotid surgery pathway prior to the NICE guidelines (July 2008).

According to NICEHow quickly do we need to investigate & Treat symptomaticCarotid Stenosis?

7 days

South East CoastStroke Clinical ReferenceGroup target for CEA

48hrs from diagnosis

Stroke and TIA Surgical Helpline – allow direct consultant to consultant referrals from HASU and acute stroke unites from RSCH, BNHH and HWPH SEND IMAGES VIA IEP and FAX PATIENT DETAILS

GPs to refer to their nearest HASU or Acute Stroke units or Rapid Access TIA clinic - MDT

Limitations of CEA Severe OA / ankylosis cervical spine Long length lesions High bifurcations (above C2) Previous cervical surgery Previous cervical irradiation Concomitant intra-cranial lesion Concomitant thoracic lesion Medically “high risk” patient

The first report of endoluminal carotid intervention“Catheter dilatation of proximal

carotid stenosis during distal bifurcation endarterectomy.”

Kerber CW et al. 1980

Am J Neuroradiol

Carotid artery stenting (CAS)

Overview of CASPatient preparation

Femoral access

Aortic arch angiogram

Selective arch vessel cannulation

Intracranial and extracranial cannulation

Common carotid sheath access

EPD placement

Predilatation, stenting and postdilatation

Completion angiogram

EPD removal

Access site management

Postprocedural care and followup

Catch of the day!

Risk of micro-emboli: CAS vs. CEA Diffusion-weighted MRI

Events in the 48 hours following CEA and CAS. 19 / 27 (70%) CAS vs. 0 / 19 (0%) CEA

9 ipsilateral / 7 bilateral / 3 contralateral

3 CAS patients had post-operative neurology but all resolved within 36 hours.

The only factor associated with the development of microemboli was the use of a diagnostic arch angiogram.

Preoperative MRI/A or CT-A recommended as alternative instead

NICE guidance for CAS

Safe and efficacious in the short term

Unsure about benefits in asymptomatic

Clear written information with consent

Audit and review all cases

Submit cases to registries and studiesLast updated September

2006

Asymptomatic carotid disease- what was known before ACST

ACAS (USA) 1995

If a patient had a CEA before developing symptoms, they might be less likely to have a stroke, providing the operation had a very low morbidity and mortalityBenefits confined to men under 65 yearsNo difference in outcome for stenosis 60-99%Benefits were not greater for those with tighter stenosis as seen in the symptomatic trials

MAJORITY OF PATIENTS IN USA & EUROPEAN SERIES ARE ASYMPTOMATIC!

ACST (UK) 2003

1560 allocated immediate CEA1560 allocated follow-up with deferred CEA3.4 years mean follow-up

Asymptomatic Carotid StudiesTotal 5 year Stroke related mortality

What we know post ACST

Benefits significant for men as well as for women up to the age of 75 years.

Benefits seen in patients with a stenosis > 70% on ultrasound.

5 year net risk of all strokes in ACST.6% with immediate CEA12% with deferred CEA

Fatal and disabling stroke, not just stroke overall was prevented by surgery.

ACST Caveats Best medical therapy (BMT) not optimised.

Higher event rates compared with medical trials. Surgeons with event rates > 3%?

CAPRIE (n= 19185) 2 yr Stroke, MI, Vascular Death 5.8% ASA vs. 5.3% Plavix

4S study (n=4444) Simvastatin 2.7% vs. Placebo 4.3%

No plaque morphology characterisation.

RCTs of CEA for asymptomatic diseasePrimary

Endpoint

Trial N Stenosis

(%)

Medical

(%)

Surgical

(%)

P value

ARR

(%)

NNT

VA

1993

444 >50 20.6 8 <0.001 3 32

ACAS

1995

1662 >60 11 5.1 0.004 1.2 85

CASANOVA

2001

410 50-90 NS NS NS NS NS

ACST

2004

3120 >60 11.8 6.4 <0.001 1.1 93

Future asymptomatic data ECST-2

Role of BMT + Surgery vs. BMT FPH will be recruiting Dr. Giosue Gulli PI

ACST -2 Role of CEA vs. CAS. Funding approved. Now recruiting.

TACIT Role of BMT vs. BMT + CEA vs. BMT + CAS

Timing of surgery and efficacy Risks of further stroke are the highest in the

first 2 weeks following TIA/Minor stroke

Early carotid surgery is safe in ASA I / II patients following stable, non-disabling stroke

Safer to delay ASA III / IV patients

Patients with large areas of brain injury on CT or MRI

Patients with unstable symptoms are at higher risk of peri-operative stroke

Future role for Best medical therapy?

Antiplatelets

NOACs

Statins

Antihypertensives

Can we go faster?RACE (Rapid Access Carotid Endarterectomy)

Follow the local Stroke/TIA pathways Refer to TIA clinic or ED Stroke units to admit high risk ABCD2 > 4 patients Fast track investigations for TIA/Stroke Surgical referral to vascular surgeon – USE

HOTLINE Inform colleagues in primary and secondary care

SummaryThe use of a stroke/TIA pathway to expedite access to assessment Imaging and treatment is mandatory.

Carotid endarterectomy remains the “gold standard” in intervention for symptomatic carotid disease.

The ideal patient group for CAS remains to be defined and long term results from ICSS and CREST are awaited. The traditional indications for CAS still hold. CAS patients should be entered into registries.

There is no place for the routine screening of patients for asymptomatic carotid disease.