Transcript Anticoagulation in Acute Stroke

Anticoagulation in Acute
Ischemic Stroke
TPA: Tissue Plasminogen Activator
1995: NINDS study of TPA administration
Design: randomized, double blind placebo-controlled study.
N=624
Dosing: 0.9mg/kg (10% bolus, 90% given over 60 minutes)
Outcomes: At 12 months tpa patients were 30% more likely to have
minimal or no disability.
1996: FDA approved TPA for acute stroke management.
Additional Studies: ECASS I/II and Atlantis: Concluded the earlier the
better (< 3hrs) and there is improved outcome if no significant infarct
on CT.
TPA: Tissue Plasminogen Activator
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Inclusion criteria:
**Clinical diagnosis of stroke with measurable deficit.
** Time: < 3 hours (based on the last time patient was seen
normal)
** Previously independent functional status.
TPA: Tissue Plasminogen Activator
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Absolute Exclusion criteria
**History:
1. CVA or head trauma 3 months prior
2. Cerebral Aneurysm or known AVM.
3. MI in the 3 months prior
4. Any history of intracranial hemorrhage
**Clinical:
1. spontaneously clearing stroke symptoms
2. BP >185 or diastolic >110.
**Labs:
1. Platelets <100,000
2. INR >1.7 on oral anticoagulants
**Radiology: Evidence of multi-lobar infarction with >33% cerebral
involvement or hemorrhage or mass on CT
TPA: Tissue Plasminogen Activator
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Relative Exclusion criteria
**History:
1. Major surgery <14 days prior
2. GI or GU bleeding <21 days prior
3. LP <7 days prior.
4. Arterial puncture at non-compressible site <7 day
prior.
**Labs: Glucose <50 or >400
Aspirin Therapy
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Aspirin: Only therapy that has been evaluated with RCTs.
Aspirin therapy given within 48 hours of onset of acute
ischemic stroke symptoms leads to a significant reduction
in the risk of early stroke recurrence/mortality, and leads
to improved long-term outcome (IST and CAST).
Recommended dose: Initial 325mg, thereafter 150mg 325mg/day. It may be used in assoc. with DVT
prophylaxis.
Contraindications: Receiving TPA, IV heparin, or oral
anticoagulants.
Alternatives: clopidogrel, ticlopidine, aggrenox.
IST ( International Stroke Trial)
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Design: Unblinded, randomized control trial.
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N= 19,435; 467 hospitals in 36 countries.
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Treatment arms:
1. no treatment
2. ASA 300mg
3. heparin 5000 units SQ BID
4. Heparin 5000 U SQ BID + ASA 300mg
5. Heparin 12,500 U SQ BID + ASA 300mg
6. Heparin 12, 500U SQ
IST ( International Stroke Trial)
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Conclusions regarding ASA therapy :
>ASA led to significantly fewer recurrent ischemic stroke.
>ASA led to decreased death and dependence at 6 months.
>ASA was NOT associated with an excess of hemorrhagic
strokes.
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Combined analyst of the IST and CAST trial: Of 1000
patients, 9 deaths/recurrent stroke are prevented with ASA
therapy in the first few weeks. 13 deaths/recurrent strokes
are prevented at 6 months.
Full anticoagulation with IV heparin
and LMWH.
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Use is not recommended by AHA/ASA and
ACCP due to limited evidence of efficacy and
increased risk of bleeding complications.
No clinical trial has yet to adequately evaluate
full dose-anticoagulation in acute stroke.
Resources:
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The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study
Group. Tissue plasminogen activator foracute ischemic stroke. N Engl J Med 1995;
333:1581–1587.
International Stroke Trial Collaborative Group. The International Stroke Trial (IST): a
randomized trial of aspirin, subcutaneous heparin, both, or neither among 19,435
patients with acute ischemic stroke. Lancet 1997; 349:1569–1581.
ACP medicine Dale and Federman et Al. 2007 2206-2212
Anti-thrombotic and Thrombolytic Therapy for Ischemic Stroke: Chest 2001;119;300S320S