Who is the man in the picture?

a) Osama Bin Laden

b) Charles Darwin

c) Loui Pasteur

d) Charles Dickens

e) Barack Hussein Obama

A Journal of the life of Charles Dickens 1869-1870

• In 1869 wrote a letter to W.H. Willis MD, mentioning difficulties speaking and moving “foot”

• Jan. 1870 new year’s day at Gad’s Hill suffering another attack of …”the foot trouble”

• Jan 23 complains: “something the matter with my right thumb…and can’t write plainly”

• June 8th : writing Edwin Drood and suffers a stroke at Dinner.

A.Tamayo U of M

TRANSIENT ISCHEMIC ATTACK

A.Tamayo U of M

Transient Ischemic Attack

From Definition to Treatment

Arturo Tamayo MD, FAHAAssistant Professor of Neurology U of MDirector of the Stroke Prevention Clinics

BRHA and WHSC

Disclosures

• Research board member and lecturer to the Heart and Stroke Foundation of Canada.

• Member of the Steering Committee of the Canadian Stroke Strategy and Consortium

• Speakers Honoraria: Pfizer, Allergan, and Schering-Plough

• NO STOCKS in pharmaceutical industry

A.Tamayo U of M

TIA… The Problem

• TIA and its implications has evolved over the last decade implicating:a) Definition

b) Risk stratification

c) Acute decision making-management

d) PrognosisA.Tamayo U of M

What is the definition of TIA?

a) Transient deficit lasting less than 24 hrs.

b) Deficit which improves (but not resolves) within 24 hours.

c) Transient deficit lasting less than 30 min.

d) Transient deficit lasting up to an hour.

e) All of the above

TIA: Definition

• TIA was defined as an episode of focal, transient neurological deficit of vascular etiology that resolve in less than 24 hrs. NINDS classification of CVD. Stroke 1990; 21:637.

• Definition NOT ANYMORE accepted

Incorrect and inaccurate

•A.Tamayo U of M

TIA: Definition

•A.Tamayo U of M

TIA The Incidence and Prevalence

•A.Tamayo U of M

• NSA sponsored telephone survey • A total of 175,000 phone calls• Only 8.6% was able to identify symptoms • 10,112 participants:

2.3% (95% CI, 2.0-2.6%) had Dx of TIA given by a physician only 64% saw a physician within 24 hrs. 2.3% were diagnosed as Stroke. 19 of them had a previous TIA.3.2% had a TIA but were not seen by a doctor

• Projecting results to US population: 4.9 million of people have been

diagnosed with TIA

Univariate analysis:

History of TIA was more common in the elderlyThose with lower income Fewer years of education

Neurology.2003;60:1429-34

•A.Tamayo U of M

• That is: In 2002: 204,000 TIAs in USA• Stroke. 2005;36:720-723. •A.Tamayo U of M

NEW DEFINITION

TRANSIENT ISCHEMIC ATTACK

TIA is a brief episode of neurological dysfunction caused by focal brain or retinal

ischemia, with complete resolution of symptoms in less than an hour and

without evidence of infarction.

NEJM. 2002; 347:1013-1016.

•A.Tamayo U of M

TIA old vs. new definition• Time Based• Deficit < 24 hours.

• Suggests Benign

• Delays Intervention

• Inaccurately predicts ischemia.

• Diverges from CAD• tPA- Could be a TIA

• Tissue Based• <1 hr event without

evidence of infarction.• Indicates potential

ischemic danger.• Encourage IMAGING and

intervention• Good ischemic predictor

• Consistent with CAD• tPA- Almost all are stroke

•A.Tamayo U of M

• Stroke 1999;30:1174

•A.Tamayo U of M

TIA… The Problem

• TIA and its implications has evolved over the last decade implicating:a) Definition

b) Risk stratification

c) Acute decision making-management

d) Prognosis•A.Tamayo U of M

Which one of the following is true?

a) TIA patients are on higher risk of stroke within 3 months

b) Most of patient with TIA present with a stroke within a week of first event

c) The risk differs if they have hemispheric or retinal symptoms

d) They are on high risk of cardiovascular problems

e) All of the above

Stroke Risk after a TIAStudy N Stroke Risk

Whisnant, et al 198 10.0%/90dJohnston, et al 1707 10.5%/90dJohnston, et al (Kaiser C) 976 8.4%/90dEliazsew (NASCET) 603 20.1%/90dPanagos, et al 790 13.3%/90dFASTER (CANADA) 150 25.0%/90dLovett, (Oxfordshire) 209 12.0%/30dBiller, et al 55 9.1% / 6 dPutman, et al 74 6.8%/6 d

Average 13.3% Stroke Risk in 90 Days after TIA

•A.Tamayo U of M

The Northern California TIA StudyJAMA.2000:13;284(22):2901-6

•Northern California Keiser district16 hospitals2.9 million coveredRepresentative of the San Francisco Bay

•Patients given diagnosis of TIA @ ER.March 1997- Feb 1998.Follow up for record review for 3 months

Settings

Cohort Study

•A.Tamayo U of M

The CohortJAMA 2000:13;284:2901-6

• N= 1707 patients. Mean 72 yo.53% females.Median spell 70 min.

• 3 months risk of stroke…… 10.5%1 week risk of stroke ……... 6.0%

• Recurrent TIA……………… 13.2%• Cardiovascular hospitaliz… 2.7%• Death……………………….. 2.6%• Any of these events………. 26.2%

A.Tamayo U of M

Higher risk of stroke within 7 days

JAMA 2000;284:2901-2906

Kaplan-Meier Survival-Free from StrokePatients Presenting with TIA in Emergency Room (N=1707)

10.5%

High risk of stroke during 1st few days after TIA

A.Tamayo U of M

What did we learn from NASCET and TIA?Eliasziw M. et al. CMAJ 2004;30:170(7)1105-9

A.Tamayo U of M

TIA STRATIFICATIONThe California TIA RISK SCALE

• Age > 60

• DM

• Duration of episode > 10 min

• Unilateral weakness

• Speech impairment

A.Tamayo U of M

The California Score

A.Tamayo U of M

Risk Stratification with ABCD2

*2-day stroke risk: 1%(0-3 points), 4% (4-5 points), 8% (6-7 points)*90 day stroke risk up to 25% Lancet 2007; 369:283-92

Age 1 point if > 60 years

Blood pressure 1 point if sBP >140 or dBP >90

Clinical features

2 points for unilateral weakness; 1 point speech deficit without weakness

Duration 2 points if >60 min; 1 point if >10-59 min

Diabetes 1 point

A.Tamayo U of M

Defining high risk.ABCD2 + MRI (DWI / intracranial vessel occlusions)

Coutts et al. Int J. Stroke 2008; Ann Neurol 2005 A. Tamayo U of M

TIA… The Problem

• TIA and its implications has evolved over the last decade implicating:a) Definition

b) Risk stratification

c) Acute decision making-management

d) PrognosisA.Tamayo U of M

TIA- is an emergency!WHEN SHOULD WE TREAT?

Half of all strokes occur in the first 2 days after TIA

Gladstone et al. CMAJ 2004 A.Tamayo U of

M

When to Treat?

• 23% of patients with ischemic stroke have had a TIA before their stroke

a) 17% occur the day of the strokeb) 9% occurred the previous dayc) 43% had a TIA during the 7 days prior

• Pooled analysis from population and RCTs (OXCASC, OCSP, UK-TIA and ECST)Rothwell & Warlow, Neurology 2005;64:817

A.Tamayo U of M

ER ASSESSMENT

• Points to remember:

• ABCD2 score has a sensibility of 80%, that is, there are 20% of patients that can be missed.

• This scale was not include patients on Atrial Fibrillation who are on extreme risk!

A.Tamayo U of M

3-Month Stroke Risk According to Etiological subtype

• Lovett et al. Neurology 2004: Meta analysis, n=1709 A.Tamayo U of M

Extracranial Vessel Disease

A.Tamayo U of M

TCD and Carotid Microemboli

A.Tamayo U of M

ANTIPLATELETS

A.Tamayo U of M

PLAVIX LOADING DOSE225-300 mg

• RationaleNOT PROVEN EXPERIENCE IN STROKE PATIENTS. ONE TRIAL ON ITS WAY. However:a) Acute coronary syndromes: Dosages between 200-300mg inhibit in 15 minutes sCD 40 ligand (sCD40L) and CRP (?).b) Better outcome.

Am Heart J. 2006; 151(2):521 e1-e4.Cure Study. Am Heart J. 2005;150(6) 1177-85.Circulation 2005.112(19):2946-2950.

A.Tamayo U of M

A.Tamayo U of M

0-2 4-122-4 >12

Time from event to randomization (weeks)

5-year ARRin stroke

(%)

Timing of Surgical InterventionTiming of Surgical InterventionThe NASCET and ECST StudiesThe NASCET and ECST Studies

• Lancet 2004;363:915-24.

30.230.2

14.814.817.617.6

3.33.3

11.411.4

44

8.98.9

-2.9-2.9

40

30

20

10

0

-10

70 to 99% stenosis

50 to 69% stenosis

NNT=3NNT=3NNT=3NNT=3

NNT=7NNT=7NNT=7NNT=7

Numbers above bars indicate actual absolute risk reduction. Vertical bars are 95% CIs

A.Tamayo U of M

CAROTID STENTING

A.Tamayo U of M

CREST TRIAL= CAE

• Brott TG. N.Engl J Med 2010;363:498

A.Tamayo U of M

Atrial Fibrillation• One of the strongest known

independent risk factor for ischemic stroke.

• Etiology usually divided into valvular and non-valvular disease and into permanent vs. paroxystic.

• Poorly organized contractions result in sluggish atrial blood flow (> left atrial appendage) favoring thrombus formation.

• Thrombi composed from deposits of fibrin and platelets.

Marder VJ, Chute DJ, Starkman S, et al. Analysis of thrombi retrieved from cerebral arteries of patients with acute ischemic stroke. Stroke 2006:37;2086-2093.

A.Tamayo U of M

2004 ACCP Guidelines for risk stratification and antithrombotic guidelines for NVAF

RiskCategory

Annual risk ofStroke

Antithrombotictherapy

High>75, prior ischemia, HBP, DM, CHF, +/- LVD

6-12%( CHADS2: 3-6 )

Warfarin(INR 2.0-3.0)

ModerateAge 65-75, none of the above.

~ 3%( CHADS2: 1-2 )

Warfarin or Aspirin

Low<65 with none of the above

~ 1%( CHADS2: 0 )

Aspirin

•Chest.2004;126:429S-456S. A.Tamayo U of M

Warfarin vs No treatment• Primary Prevention• Five major primary

prevention trials consistently showed:a) RRR 68% per year.b) NNT 32c) Reduced combined outcome by 48% (stroke, systemic embolism or death)

• Ezekowitz MD. N Engl J Med.1992;327:1406-1412

• Secondary Prevention• Secondary stroke

prevention RRR by 66% (12% risk in untreated vs 4% treated).

• NNT 13• No hemorrhagic

differences among groups

• EAFT Study. Lancet. 1993;342:1255-1262

A.Tamayo U of M

Hylek EM. N Engl J Med. 2003;349:1019-1026.

A.Tamayo U of M

Stroke or systemic embolism (SSE)

0.50 0.75 1.00 1.25 1.50

Dabigatran 110 mg vs. warfarin

Dabigatran 150 mg vs. warfarin

Noninferiorityp-value

<0.001

<0.001

Superiorityp-value

0.34

<0.001

Ma

rgin

= 1

.46

HR (95% CI)Connolly SJ., et al. NEJM published online on Aug 30th 2009. DOI 10.1056/NEJMoa0905561

Dabigatran etexilate is in clinical development and not licensed for clinical use in stroke prevention for patients with atrial fibrillation

A.Tamayo U of M

Vascular RisksHYPERTENSION

• The most important modifiable risk factor (2-5x)Ischemic bleeding,Silent strokes

• Contributes toLarge vessel diseaseSmall vessel (lacunar)LV dysfunction

• Treatment reduces risk 40%

• CHEP: • <140/90 (in DM <130/80)

Stroke. 2006;37:577-617

A.Tamayo U of M

Vascular Risks

• Diabetes: Increases x 2 the risk of Stroke. Highly correlated with HTN, and metabolic syndrome.Treatment reduces microvascular complications>macrovascular.

• Cholesterol: Doubles the risk of stroke. Risk for CAD. SPARCL (NNT = 50)

A.Tamayo U of M

TIA… The Problem

• TIA and its implications has evolved over the last decade implicating:a) Definition

b) Risk stratification

c) Acute decision making-management

d) PrognosisA.Tamayo U of M

EXPRESS StudyRothwell et al. Lancet 2007

• Phase 1 vs. 2• 90 days stroke risk

from 10% to 2%• Medications started

right away• Carotid

endarterectomy expedited

A. Tamayo U of M

RECOMMENDATIONS IN THE ER: The Never and Ifs’ rules

• NEVER FORGET THE TIA CANADIAN GUIDELINES • Play SAFE! (never play un-safe)• Never discharge If not sure; consult Neurologist on Call!• Never discharge a patient unless mayor risk factors and

images have been done. (managing hypertension, hyperglycemia, electrolytes imbalance) and CT of brain and carotid images are available. If severe stenosis consult neurology.

• Never discharge a patient with crescendo TIAs• Never discharge a patient with mild deficits (that is a

stroke)• Never discharge a patient on Atrial Fib.

A.Tamayo U of M

My Recommendations in ER (2)

• If ABCD2 score is 0-3 points and patient is stable; REFERRAL TO STROKE CLINIC(all patients should be seen within 3 days)

• If ABCD2 score is 4-5; patient should be seen in ER by Neurology.

• If large or small vessel disease is suspected: load patient with Clopidogrel (75mg x 3).

• If Patient is on Atrial Fibrillation: Patient should be admitted on IV heparin and a transesophageal echo should be requested to rule out: Atrial appendage thrombus

A.Tamayo U of M

Current Research

• A) TIA Hotline• B) Triage TIA scale

Project designer: Susan Alcock RN (WRHA)

Brandon-Winnipeg Stroke Clinic Team

MANITOBA STROKE PREVENTION CLINICS

• Brandon Regional Health CentreTel: 578 - 2165 Fax: 578 - 4956• Steinbach Regional Health CentreTel: 320 - 4177 Fax:320 - 4171• Winnipeg Health Sciences CentreTel: 787-1121 Fax: 787- 3803• Winnipeg St. Boniface Health CentreTel: 235 – 330 Fax: 233 - 3285

A.Tamayo U of M

Any Questions?

• Thank you!