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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)

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Tpa tissue plasminogen activator
TPA: Tissue Plasminogen Activator

1995: NINDS study of TPA administration

Design: randomized, double blind placebo-controlled study.


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 activator1
TPA: Tissue Plasminogen Activator

  • 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 activator2
TPA: Tissue Plasminogen Activator

  • Absolute Exclusion criteria


    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


    1. spontaneously clearing stroke symptoms

    2. BP >185 or diastolic >110.


    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 activator3
TPA: Tissue Plasminogen Activator

  • Relative Exclusion criteria


    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
Aspirin Therapy

  • 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
IST ( International Stroke Trial)

  • Design: Unblinded, randomized control trial.

  • N= 19,435; 467 hospitals in 36 countries.

  • 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 trial1
IST ( International Stroke Trial)

  • 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.

  • 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
Full anticoagulation with IV heparin and LMWH.

  • 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.


  • 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;300S-320S