TIA: Opportunity for Prevention

1
TIA Opportunity for Prevention

• 2009 Cardiovascular Health Summit
• Nicholas J. Okon, D.O.
• Vascular Neurologist
• Billings, MT
• Portland, OR

2
Overview

• TIA represents ideal opportunity for preventing
  stroke
• Very hi risk of stroke after TIA in first 48 hrs
• ABCD2 score allows accurate prediction of risk
• Time for a paradigm shift in the evaluation and
  treatment of TIA and minor stroke victims
• Hi risk of future vascular events and vascular
  death in TIA and stroke patients
• Future direction

3
TIA Opportunity for Prevention

• Stroke is ideally suited for prevention
• High prevalence
• High economic cost
• High burden of illness
• Preventive measures are safe and efficacy has
  been validated

Gorelick PB. Stroke 199425220-224
4
TIA Opportunity for Prevention

• TIA represents the best opportunity to intervene
  and prevent stroke.
• Inconsistent approach to management in the ED
  throughout US
• Recent refinement of short term-risk (48hr)
  allows for application of systematic approach

5
TIA Public Health Burden

• 4.9 Million people in the US report being
  diagnosed with TIA
• An est. 2.3 US adults experience TIA
• Many more recall symptoms consistent with TIA but
  did not seek medical attention

Neurology SC Johnston 2003601429-34
6
Stroke Public Health Burden

• Approximately 11 of patients diagnosed with TIA
  in the ED will have a stroke in 90 days
• 15-20 of patients with stroke have a preceding
  TIA
• 15-20 of patients with stroke have had a
  preceding minor stroke
• Additional 4.9 Million people in the US report
  being diagnosed with stroke
• Similar prevalence of stroke-2.3 US adults

Neurology SC Johnston 2003601429-34
7
Knowledge of TIA

• Only 8.2 of US adults able to identify correct
  definition of TIA
• Only 8.6 of US adults able to recognize at least
  one common symptom of TIA
• Older age, lower income and fewer years of
  education predict TIA and stroke

Neurology SC Johnston 2003601429-34
8
Case Mr. JM

• 68 y/o male smoker with recently diagnosed HTN
  presents to local ED with 20 minutes right
  hemiparesis and speech changes 4 hours ago.

9
CaseMr. JM

• Incomplete history taken by ED provider
• BP 150/90
• NL limited neurologic exam
• CT head read as normal
• No contact with Neurologist
• Patient discharged from ED with instructions to
  follow up with Primary provider /- Aspirin

10
CaseMr. JM

• Whats Mr. JMs diagnosis? TIA or Minor stroke?
• What is his risk of stroke after this event?
• What other testing should be performed and when?
• What is the best method for prevention?

11
How is TIA defined?

• Classic definition of TIA
• sudden, focal neurologic deficit lasting lt 24
  hrs.
• presumed to be of vascular origin
• confined to an area of the brain or eye perfused
  by a specific artery

12
Problems with classic definition of TIA

• presumes that if symptoms resolve completely then
  no permanent ischemic damage has occurred
  suggesting that TIAs are benign
• 24 hr criterion is arbitrary and assumes that if
  symptoms last gt24 hrs an injury to brain
  parenchyma should be detectable by microscopy
• numerous studies have shown (since 1958) that the
  majority of TIAs last lt 1 hour

13
New Definition of TIA
The TIA Working Group N Engl J Med
200230(11)2502

• A TIA is a brief episode of neurologic
  dysfunction caused by focal brain or retinal
  ischemia, with clinical symptoms typically
  lasting less than one hour, and without evidence
  of acute infarction

14
New Definition of TIA further clarification

• Patients who have transient focal symptoms of
  brain ischemia -- and who, on diagnostic
  evaluation, are found to have an acute
  infarction-- would no longer be classified as
  having a TIA, regardless of the duration of
  clinical symptoms.

The TIA Working Group N Engl J Med
200230(11)2502
15
CaseMr. JM

• Whats Mr. JMs diagnosis? TIA or Minor stroke?
  --TIA.
• What is his risk of stroke after this event?
• What other testing should be performed and when?
• What is the best method for prevention?

16
Risk of stroke after TIA
17
Long-Term Risk of StrokePercentage of Patients
Experiencing Stroke
Feinberg WM, Albers GW, Barnet HJM, et al. Stroke
199425(6)1320-35. Sacco RL. Neurology
199749(Suppl 4)S39-S44. Sacco RL, Shi T,
Zamanillo MC, et al. Neurology 199444626-34. Bro
derick J, Brott T, Kothari R, et al. Stroke
199829415-21.
18
Short-term prognosis after ED diagnosis of TIA

• 1707 patients diagnosed with TIA by ED docs
• 99 presented in 24 hrs
• 50 had symptoms upon arrival to ED
• 21 of strokes were fatal 64 were disabling

SC Johnston JAMA 20002842901-2906
19
1707 patients identified by ED docs with TIA
among 16 hospital in HMO in northern California.
SC Johnston JAMA 20002842901-2906
20
90 Day Risk of Stroke After TIA Increases with
Number of Risk Factors
SC Johnston JAMA 20002842901-2906
Risk Factors Age gt 60 y Diabetes Symptoms gt 10
min Weakness Speech Impairment
21
ABCD score
Rothwell,PM Lancet 2005 Jul 2-8366(9479)29-36

• Score derived for 7-day risk of stroke in
  population-based cohort of patients with TIA
  (Oxfordshire CommunityStroke Project)
• Further validated in the Oxford Vascular Study
• 6-point clinical-based score proved highly
  predictive of 7 day risk of stroke

22
ABCD score
Rothwell,PM Lancet 2005 Jul 2-8366(9479)29-36
23
ABCD score
Rothwell,PM Lancet 2005 Jul 2-8366(9479)29-36
24
ABCD2 score
Johnston SC, Rothwell,PM Lancet 2007 Jan
27369(9558)283-92
25
ABCD2 score
Johnston SC, Rothwell,PM Lancet 2007 Jan
27369(9558)283-92

• Age gt 60 years 1
  pt.
• BP gt 140/90 or DBP gt 90 1 pt.
• Clinical
• Focal/Unilateral Weakness or 2
  pt.
• Speech impairment
  1 pt.
• Duration of Symptoms
• gt 60 minutes or
  2 pt.
• 10-59 minutes
  1 pt.
• Diabetes Mellitus 1 pt.

26
ABCD2 score
Johnston SC, Rothwell,PM Lancet 2007 Jan
27369(9558)283-92
27
ABCD2 score

• Age gt 60 years (1 pt.)
  1
• BP gt 140/90 or DBP gt 90 (1 pt.) 1
• Clinical
• Focal/Unilateral Weakness or (2 pt.)
  2
• Speech impairment (1 pt.)
• Duration of Symptoms
• gt 60 minutes or (2 pts.)
• 10-59 minutes (1 pt.)
  1
• Diabetes Mellitus (1 pt.)
  0
• Total 5

28
CaseMr. JM

• Whats Mr. JMs diagnosis? TIA or Minor stroke?
  --TIA.
• What is his risk of stroke after this event? gt4
  in 48hrs
• What other testing should be performed and when?
• What is the best method for prevention?

29
Risk of stroke after TIA also dependent on cause
Lovett, JK (Oxfordshire) Neurology 200462569-74
30
Nearly half of highest 90 day risk occurs in
first 48hrs --5.5)
48 hrs
48 hrs
31
CaseMr. JM

• Whats Mr. JMs diagnosis? TIA or Minor stroke?
  --TIA.
• What is his risk of stroke after this event? gt4
  in 48hrs
• What other testing should be performed and when?
  Labs (cholesterol,FBG,CBC), Brain MRI and head
  and neck vascular imaging (MRA,CTA,US) and
  echocardiography (TTE/-TEE) lt48 hrs.
• What is the best method for prevention?

32
Time for a paradigm shift in the evaluation and
treatment of TIA and minor stroke victims
33
Effect of urgent treatment of transient ischemic
attack and minor stroke on early recurrent stroke
(EXPRESS study)
Rothwell, PM Lancet 2007370 (9596)1432-1442

• Population-based study of pre (Phase 1) and post
  (Phase 2) implementation of urgent assessment and
  immediate treatment in clinic in patients with
  TIA and minor stroke not admitted to hospital
• Phase 1 PCPs made referral, visit then scheduled
  by specialty clinic and recommendations faxed
  back to PCP after evaluation
• Phase 2 PCPs sent patients directly to specialty
  clinic after presentation without referral or
  appointment and treatment initiated in the
  specialty clinic

34
Effect of urgent treatment of transient ischemic
attack and minor stroke on early recurrent stroke
(EXPRESS study)
Rothwell, PM Lancet 2007370 (9596)1432-1442

• Median delay to clinic assessment fell from 3 to
  1 day
• Median delay to first prescription fell from 20
  to 1 day
• 80 reduction in 90 day risk of early recurrent
  stroke

35
A transient ischemic attack clinic with
round-the-clockaccess (SOS-TIA) feasibility and
effects
Lancet Neurol 20079953-60

• 1085 TIA patients calling toll-free phone then
  seen at hospital clinic with 24 hr access in
  Paris,France
• 53 seen lt24 hrs from symptom onset
• 65 with TIA or minor stroke
• Standard assessment lt4 hrs after admission
• 87 seen by vascular neurologist lt24 hrs from
  phone call
• 90 day and 1 yr outcomes compared to ABCD2
  predicted outcome

36
A transient ischemic attack clinic with
round-the-clockaccess (SOS-TIA) feasibility and
effects
Lancet Neurol 20079953-60

• 26 admitted to stroke unit, 76 D/Cd same-day
  of evaluation
• 95 had brain, arterial and cardiac imaging
• Cause identified in 41 of those with normal
  brain imaging 64 with minor stroke 74 with
  TIA and abnormal brain imaging
• All patients received 300-500mg ASA
• Goals for secondary prevention faxed to PCP after
  direct communication by phone and before d/c

37
A transient ischemic attack clinic with
round-the-clockaccess (SOS-TIA) feasibility and
effects
Lancet Neurol 20079953-60

• Antithrombotics given immediately in 98
• BP meds started or modified in 24
• Lipid lowering therapy started or modified in 45
• gt75 patients with atrial fibrillation received
  anticoagulants
• 5 needed carotid revascularization and received
  it lt 6 days form initial evaluation

38
A transient ischemic attack clinic with
round-the-clockaccess (SOS-TIA) feasibility and
effects

• 90 day stroke rate 1.24 vs. 5.96 ABCD2
  predicted
• 1 year rate of MI and vascular death 50 less
  than reported meta-analysis (1.1 vs. 2.2)

Lancet Neurol 20079953-60
39
Hi risk of future vascular events and vascular
death in TIA and stroke patients
40
Risk of Myocardial Infarction and Vascular Death
AfterTransient Ischemic Attack and Ischemic
StrokeA Systematic Review and Meta-Analysis
Touze,E Stroke 2005362748

• Meta-analysis of 39 studies including 66,000
  patients with mean follow up of 3.5 years
• 2.1 annual risk of nonstroke vascular death
• 2.2 annual risk of total MI (fatal and non)

41
Long-term survival and vascular event risk after
TIA or minor stroke LiLAC (Life Long After
Cerebral ischemia) Study
Lancet 20053652098-104

• 10 yr follow-up of Dutch TIA Trial
• 2473 TIA or minor strokes lt 3 month randomized to
  ASA 30mg or 283 from 1986-89
• cardio-embolic and clotting disorders excluded
• TIA defined as lt24 hrs

42
Long-term survival and vascular event risk after
TIA or minor stroke LiLAC (Life Long After
Cerebral ischemia) Study

• 60 died of vascular causes at 10 yrs.
• 54 experienced at least 1 new vascular event
• Event-free survival 48 at 10 years

Lancet 20053652098-104
43
Long-term survival and vascular event risk after
TIA or minor stroke LiLAC (Life Long After
Cerebral ischemia) Study
Lancet 20053652098-104
44
Long-term survival and vascular event risk after
TIA or minor stroke LiLAC (Life Long After
Cerebral ischemia) Study
Lancet 20053652098-104

• Strongest predictors of all cause death
• Agegt 65
• Diabetes
• Hx claudication or prior PVD surgery
• Abnormal baseline ECG

45
CaseMr. JM

• Whats Mr. JMs diagnosis? TIA or Minor stroke?
  --TIA.
• What is his risk of stroke after this event? gt4
  in 48hrs
• What other testing should be performed and when?
  Labs (cholesterol,FBG,CBC), Brain MRI and head
  and neck vascular imaging (MRA,CTA,US) and
  echocardiography (TTE/-TEE) lt48 hrs. Lower
  extremity arterial doppler.
• What is the best method for prevention?

46
Future Direction

• Combining multiple therapeutic strategies for
  secondary prevention

47
Combining Multiple Approaches for the Secondary
Prevention of Vascular Events After Stroke
Stroke 2007381881-1885

• Quantitative modeling study using published
  meta-analyses of RCTs of secondary prevention and
  hi-risk primary prevention of vascular events
• Baseline rates of vascular events taken from
  LiLAC study
• Calculated cumulative relative risk and absolute
  risk reductions assuming a multiplicative scale
• Used 5 risk-reducing strategies with the broadest
  applicability to patients with stroke and TIA
  dietary modification, exercise, aspirin, statins
  and antihypertensive therapy

48
Calculated cumulative risk reduction for
implementing diet, exercise, aspirin, statins,
and antihypertensive therapy
Stroke 2007381881-1885
ARR 20 NNT5
ARR 35 NNT3
80
82
49
Combining Multiple Approaches for the Secondary
Prevention of Vascular Events After Stroke
Stroke 2007381881-1885

• Combining 5 key strategies reduces the risk of
  recurrent vascular events by gt 80 in patients
  with history of TIA or stroke.
• Only 5 patients need to be treated to prevent 1
  major vascular event over 5 years.
• Intensified management with ASAER dipyridamole,
  intensive BP lowering and hi-dose statins lead to
  gt 90 cumulative risk reduction.

50
CaseMr. JM

• Whats Mr. JMs diagnosis? TIA or Minor stroke?
  --TIA.
• What is his risk of stroke after this event? gt4
  in 48hrs
• What other testing should be performed and when?
  Vascular imaging lt48 hrs.
• What is the best method for prevention?
  Combination medical therapy with exercise and
  dietary modification

51
Summary

• Hi short-term risk of stroke after TIA requires
  urgent and expedient evaluation and immediate
  initiation of secondary prevention therapies
• Specialized 24-hr appointment-less access clinics
  superior to current standard practice
• Hi risk of vascular events and vascular death in
  TIA and minor stroke patients demands expanding
  scope of evaluation to include additional
  vascular beds
• Multimodal/combination drug therapy with exercise
  and diet modification holds promise of
  substantial risk reduction