Presentation_Okon_Updated

					TIA: Opportunity for
     Prevention
  2009 Cardiovascular Health Summit
        Nicholas J. Okon, D.O.
         Vascular Neurologist
             Billings, MT
            Portland, OR
                  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
       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 1994;25:220-224
      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
 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 2003;60:1429-34
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 2003;60:1429-34
 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 2003;60:1429-34
      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.
       Case:Mr. 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
        Case:Mr. JM
• What’s Mr. JM’s 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?
   How is TIA defined?
• Classic definition of TIA:
   • sudden, focal neurologic deficit lasting <
      24 hrs.
   • presumed to be of vascular origin
   • confined to an area of the brain or eye
      perfused by a specific artery
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 >24 hrs an injury to brain
  parenchyma should be detectable by
  microscopy
• numerous studies have shown (since 1958)
  that the majority of TIAs last < 1 hour
  New Definition of TIA
    The TIA Working Group N Engl J Med 2002;30(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”
 New Definition of TIA: further
        clarification
    The TIA Working Group N Engl J Med 2002;30(11):2502



• “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.”
        Case:Mr. JM
• What’s Mr. JM’s 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?
Risk of stroke after
        TIA
           Long-Term Risk of Stroke:
            Percentage of Patients
             Experiencing Stroke


                           After TIA      After Stroke
        30 days              4-8%             3-10%
         1 year            12-13%            10-14%
        5 years            24-29%            25-40%


      Feinberg WM, Albers GW, Barnet HJM, et al. Stroke
                       1994;25(6):1320-35.
       Sacco RL. Neurology 1997;49(Suppl 4):S39-S44.
Sacco RL, Shi T, Zamanillo MC, et al. Neurology 1994;44:626-34.
  Broderick J, Brott T, Kothari R, et al. Stroke 1998;29:415-21.
 Short-term prognosis after ED
        diagnosis of TIA
         SC Johnston JAMA 2000;284:2901-2906

• 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
1707 patients identified by ED docs with
   TIA among 16 hospital in HMO in
          northern California.
       SC Johnston JAMA 2000;284:2901-2906
  90 Day Risk of Stroke After TIA Increases
        with Number of Risk Factors
              SC Johnston JAMA 2000;284:2901-2906



   Risk Factors
    Age > 60 y
     Diabetes
Symptoms > 10 min
    Weakness
Speech Impairment
         ABCD score
   Rothwell,PM Lancet 2005 Jul 2-8;366(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
      ABCD score
Rothwell,PM Lancet 2005 Jul 2-8;366(9479):29-36
      ABCD score
Rothwell,PM Lancet 2005 Jul 2-8;366(9479):29-36
           ABCD 2                score
Johnston SC, Rothwell,PM Lancet 2007 Jan 27;369(9558):283-92
              ABCD 2            score
Johnston SC, Rothwell,PM Lancet 2007 Jan 27;369(9558):283-92
 •   Age > 60 years                            1 pt.

 •   BP > 140/90 or DBP > 90                    1 pt.

 •   Clinical:
      •   Focal/Unilateral Weakness or          2 pt.

      •   Speech impairment                    1 pt.

 •   Duration of Symptoms:
      •   > 60 minutes or                     2 pt.

      •   10-59 minutes                       1 pt.

 •   Diabetes Mellitus                        1 pt.
           ABCD 2                score
Johnston SC, Rothwell,PM Lancet 2007 Jan 27;369(9558):283-92
                     ABCD2             score

•   Age > 60 years (1 pt.)                        1

•   BP > 140/90 or DBP > 90 (1 pt.)               1

•   Clinical:

      •    Focal/Unilateral Weakness or (2 pt.)   2

      •    Speech impairment (1 pt.)

•   Duration of Symptoms:

      •    > 60 minutes or (2 pts.)

      •     10-59 minutes (1 pt.)                 1

•   Diabetes Mellitus (1 pt.)                     0

                     •    Total                   5
        Case:Mr. JM
• What’s Mr. JM’s diagnosis? TIA or
  Minor stroke? --TIA.
• What is his risk of stroke after this
  event? >4% in 48hrs
• What other testing should be performed
  and when?
• What is the best method for prevention?
Risk of stroke after TIA also
   dependent on cause
  Lovett, JK (Oxfordshire) Neurology 2004;62:569-74
Nearly half of highest 90 day risk
  occurs in first 48hrs --5.5%)




 48 hrs          48 hrs
           Case:Mr. JM
•   What’s Mr. JM’s diagnosis? TIA or Minor stroke? --
    TIA.
•   What is his risk of stroke after this event? >4% 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) <48 hrs.
•   What is the best method for prevention?
Time for a paradigm shift in the
evaluation and treatment of TIA
   and minor stroke victims
Effect of urgent treatment of transient ischemic
   attack and minor stroke on early recurrent
            stroke (EXPRESS study)
           Rothwell, PM Lancet 2007;370 (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
  Effect of urgent treatment of transient
ischemic attack and minor stroke on early
    recurrent stroke (EXPRESS study)
       Rothwell, PM Lancet 2007;370 (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
 A transient ischemic attack clinic with
            round-the-clock
access (SOS-TIA): feasibility and effects
                 Lancet Neurol 2007;9:953-60
  •   1085 TIA patients calling toll-free phone # then seen
      at hospital clinic with 24 hr access in Paris,France
  •   53% seen <24 hrs from symptom onset
  •   65% with TIA or minor stroke
  •   Standard assessment <4 hrs after admission
  •   87% seen by vascular neurologist <24 hrs from
      phone call
  •   90 day and 1 yr outcomes compared to ABCD2
      predicted outcome
 A transient ischemic attack clinic with
            round-the-clock
access (SOS-TIA): feasibility and effects
                Lancet Neurol 2007;9:953-60

  •   26% admitted to stroke unit, 76% D/C’d 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
A transient ischemic attack clinic with round-
                 the-clock
  access (SOS-TIA): feasibility and effects
                 Lancet Neurol 2007;9:953-60

•   Antithrombotics given immediately in 98%
•   BP meds started or modified in 24%
•   Lipid lowering therapy started or modified in
    45%
•   >75% patients with atrial fibrillation received
    anticoagulants
•   5% needed carotid revascularization and
    received it < 6 days form initial evaluation
 A transient ischemic attack clinic with
            round-the-clock
access (SOS-TIA): feasibility and effects
            Lancet Neurol 2007;9:953-60

  • 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%)
Hi risk of future vascular events
and vascular death in TIA and
         stroke patients
 Risk of Myocardial Infarction and Vascular Death
                       After
  Transient Ischemic Attack and Ischemic Stroke
     A Systematic Review and Meta-Analysis

             Touze,E Stroke 2005;36:2748


• 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)
  Long-term survival and vascular event
risk after TIA or minor stroke: LiLAC (Life
   Long After Cerebral ischemia) Study
             Lancet 2005;365:2098-104


• 10 yr follow-up of Dutch TIA Trial
• 2473 TIA or minor strokes < 3 month
  randomized to ASA 30mg or 283 from
  1986-89
• cardio-embolic and clotting disorders
  excluded
• TIA defined as <24 hrs
  Long-term survival and vascular event
risk after TIA or minor stroke: LiLAC (Life
   Long After Cerebral ischemia) Study
            Lancet 2005;365:2098-104


• 60% died of vascular causes at 10 yrs.
• 54% experienced at least 1 new
   vascular event
• Event-free survival 48% at 10 years
  Long-term survival and vascular event
risk after TIA or minor stroke: LiLAC (Life
   Long After Cerebral ischemia) Study
            Lancet 2005;365:2098-104
  Long-term survival and vascular event
risk after TIA or minor stroke: LiLAC (Life
   Long After Cerebral ischemia) Study
             Lancet 2005;365:2098-104


• Strongest predictors of all cause death:
         •   Age> 65
         •   Diabetes
         •   Hx claudication or prior PVD surgery
         •   Abnormal baseline ECG
           Case:Mr. JM
•   What’s Mr. JM’s diagnosis? TIA or Minor stroke? --
    TIA.
•   What is his risk of stroke after this event? >4% 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) <48 hrs. Lower
    extremity arterial doppler.
•   What is the best method for prevention?
   Future Direction
Combining multiple therapeutic strategies for
          secondary prevention
     Combining Multiple Approaches for the
    Secondary Prevention of Vascular Events
                 After Stroke
                   Stroke 2007;38:1881-1885

•   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
Calculated cumulative risk reduction for
 implementing diet, exercise, aspirin,
 statins, and antihypertensive therapy
            Stroke 2007;38:1881-1885




         ARR 20%                 ARR 35%
                                           80%
          NNT=5                   NNT=3

                        82%
 Combining Multiple Approaches for the
Secondary Prevention of Vascular Events
             After Stroke
              Stroke 2007;38:1881-1885

• Combining 5 key strategies reduces the risk of
  recurrent vascular events by > 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 ASA+ER
  dipyridamole, intensive BP lowering and hi-
  dose statins lead to > 90% cumulative risk
  reduction.
        Case:Mr. JM
• What’s Mr. JM’s diagnosis? TIA or
  Minor stroke? --TIA.
• What is his risk of stroke after this
  event? >4% in 48hrs
• What other testing should be performed
  and when? Vascular imaging <48 hrs.
• What is the best method for prevention?
  Combination medical therapy with
  exercise and dietary modification
               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

				
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