Acute Medical Stroke Therapy

1
Acute Medical Stroke Therapy

• Gregory W. Albers, MD
• Professor of Neurology and Neurological Sciences
• Director, Stanford Stroke Center

2
Acute Medical Treatment of Stroke

• Restore Blood Flow
• Thrombolytics
• Mechanical devices
• ? Stroke progression or recurrent
  thromboembolism
• Anticoagulants
• Antiplatelet agents

3
How would you treat this patient?
72 yo male with aphasia and right
hemiparesis NIH 18

• If he presents at 2 hours?
• If he presents at 5 hours?

4
How would you treat this patient?
72 yo male with aphasia and right
hemiparesis NIH 18

• Size of ischemic core?
• Size of penumbra?
• Location of vessel occlusion?

5
NINDS tPA Stroke Trial
New England Journal, 1995
Hemorrhage
p lt .05
31
20
9
20
8
1
tPA
tPA
Placebo
Placebo
NIHSS Excellent Recovery ()
Total Death Rate ()
6
Large Randomized Trials of IV tPA for Treatment
of Acute Stroke

• Study N Dose Time
  Window
• ECASS I 650 1.1 0 6
• NINDS 624 0.9 0 3
• ECASS II 800 0.9 0 6
• ATLANTIS A 142 0.9 0 6
• ATLANTIS B 619 0.9 3 5

7
Pooled Analysis

• Odds Ratios for Favorable Outcome
• Time Odds Ratio 95 (CI)
  Interval
• 0-90 2.8 1.8 - 4.5
• 91-180 1.5 1.1 - 2.1
• 181-270 1.4 1.1 - 1.9
• 271-360 1.2 0.9 - 1.5

8
NINDS tPA Trial
Distribution of Early Ischemic Changes (EIC)
on CT Scans at Baseline (N616)
Type of EIC, No. ()
Any EIC 194 (31) Loss of GWMD 164
(27) Presence of hypodensity 54
(9) Compression of CSF spaces 89 (14) Loss
of GWMD gt1/3 MCA 77 (13) Hypodensity gt1/3
MCA 14 (2) Compression of CSF gt 1/3 MCA
54 (9) Extent of EIC ? 1/3 MCA 84 (14) ?
1/3 MCA 110 (18) None 422 (69)
Patel SC, et al. JAMA. 20012862830-2838
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Stroke Code

• Who is eligible for tPA?
• What needs to be checked before starting the tPA
  infusion?
• Common errors to avoid

10
Early Infarct Signs Guidelines for Patients with
Clearly Established Stroke Onset and Treatment
Within 3 hrs

• tPA eligible
• not predictive of an unfavorable response to
  tPA
• insufficient data
• withholding tPA recommended (Level C data )

Subtle early infarct signs
(regardless of size) Extensive and clearly
identifiable hypodensity (gt1/3 MCA territory)
11
Stroke Code

• Who is eligible for tPA?
• What needs to be checked before starting the tPA
  infusion?
• Common errors to avoid

12
Stroke Code

• Nursing if patient is found to have symptoms of
  a stroke
• Confirm symptoms with resource RN immediately
• Resource RN calls primary team
• Pts RN calls Page Operator to initiate Stroke
  Code
• Then gather
• Brief history
• Reason for thinking patient had a stroke
• Last time patient seen normal
• Current vital signs

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Stroke Code

• Neurology Resident will be paged by page
  operator on stroke code pager with text message
  Stroke Code Room xxxx
• Must respond to bedside within 5 minutes
• If patient is thought to be having a stroke then
• Activate Brain Attack Team (BAT) Code Immediately

14
Stroke Code

• Brain Attack Team consists of
• Critical Care Crisis RN
• CT Tech
• Transport
• Nursing Supervisor
• Stroke Fellow/Attending (specify)

15
Stroke Code

• Neurology Resident
• Carries stroke code pager
• Responds to Stroke Code immediately
• Determines if Brain Attack Team (BAT) needs to be
  activated
• If yes
• Orders labs
• Orders CT or MRI
• EKG if needed
• NIHSS

16
Stroke Code

• Stroke Fellow/Attending
• CT or MRI scan evaluation
• Determines if tPA criteria is met or if
  Neurosurgery/Neuroradiology needs to be consulted
• Confirms NIHSS
• Writes tPA orders if appropriate
• Family communication and consent

17
How Often Should Full Dose Anticoagulation Be
Used for Treatment of Acute Stroke?

• A. Often used for multiple stroke subtypes
• B. Rarely used, except for cardioembolic
• C. Rarely used for any stroke subtype

18
Guidelines for Anticoagulant Therapy
American Heart Association, 2003

• Urgent administration of anticoagulants has
  not yet been associated with lessening the risk
  of early recurrent stroke or improving outcomes.
  Because it can increase the risk of brain
  hemorrhage, routine use cannot be recommended.

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Guidelines for Anticoagulant Therapy
American Academy of Neurology / AHA, 2003

• Anticoagulants are not recommended for any
  subgroup of patients with acute stroke based on
  any presumed mechanism or location (e.g.,
  cardioembolic, large vessel atherosclerotic,
  vertebrobasilar, or progressing stroke) because
  data are insufficient.

20
Anticoagulation for Acute Stroke
Duke, Ann Int Med 1986

• Heparin in Acute Stable Stroke (n212)
• Stroke progression Improvement
• Placebo 20 24
• Heparin 17 27

21
International Stroke TrialRecurrent Stroke
Within 14 Days(N 19,435)

22
Nadroparin (Fraxiparin) Stroke Studies
23
TOAST Study
24
TOAST Study
25
Treatment of Acute Cardioembolic Stroke
26
Recent Trial Results

• Trial Recurrent Stroke ()
• IST (AF subgroup) Heparin 2.8
• (N 3169) No heparin 4.9
• TOAST (cardioembolism) Danaparoid 0
• (N 266) Placebo 1.6
• HAEST (all with AF) Dalteparin 8.5
• (N 449) Aspirin 7.5
• TAIST HD Tinzaparin 3.3
• (N 1484) LD Tinzaparin 4.7
• Aspirin 3.1

no benefit in cardioembolism subgroup
27
Treatment of Acute Cardioembolic Stroke

• Risk of Early Stroke Recurrence
• Multiple recent emboli
• Mechanical heart valve
• Atrial fibrillation high risk features
• Established intra-cardiac thrombus

28
Treatment of Acute Cardioembolic Stroke

• Risk of Hemorrhagic Complications
• Anticoagulation increases the risk of
  extracranial hemorrhage by about 2
• Spontaneous hemorrhagic transformation is common
  and usually asymptomatic
• Anticoagulation increases the risk of symptomatic
  ICH by about 2

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Treatment of Acute Cardioembolic Stroke

• Risk Factors for Symptomatic ICH
• Infarct size
• Timing of reperfusion (12 - 48 hours)
• Excesssive anticoagulation / tPA
• Heparin bolus?
• Severe hypertension?

30
Aspirin forTreatment of Acute Stroke

• International Stroke Trial (IST, N
  19,435)
• Chinese Acute Stroke Trial (CAST N 21,106)

31
International Stroke TrialRecurrent Stroke
Within 14 Days
32
International Stroke Trial
33
Guidelines for Aspirin Therapy
Acute Ischemic Stroke

• Early aspirin therapy (160-325 mg/day) is
  recommended Grade 1A
• Delay aspirin for at least 24 hours after tPA
• Aspirin can be used safely in combination with
  low doses of subcutaneous heparin

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Guidelines for Acute Stroke Therapy
ACCP, 2004

• tPA is recommended for eligible patients within
  3 hours of stroke onset Grade 1A
• Aspirin is recommended for non-tPA eligible
  patients Grade 1A
• Use of full-dose anticoagulation with
  intravenous, subcutaneous, or low molecular
  weight heparins or heparinoids should be avoided
  Grade 2B