Journal Conference

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Journal Conference

• 2003-10-14
• ???????
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Emergent Use of Anticoagulation for Treatment of
Patients With Ischemic Stroke

• Stroke. 33(3)856-861, March 2002.

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Trials for Anticoagulants in Acute Ischemic
Stroke

• FISS
• Fraxiparine Ischemic Stroke Study (N Engl J Med.
  1995 333 15881593)
• IST
• International Stroke Trial (Lancet. 1997 349
  15691581)
• TOAST
• Trial of Org 10172 in Acute Stroke Treatment
  (JAMA. 1998 279 12651272)
• FISS-bis
• second Fraxiparine Ischemic Stroke Study
  (Cerebrovasc Dis. 1999 9 1623)
• HAEST
• Heparin Aspirin Ischemic Stroke Trial (Lancet.
  2000 355 12051210)
• TOPAS
• Therapy of Patients With Acute Stroke (Stroke.
  32(1)22-29, January 2001)
• TAIST
• Tinzaparin in Acute Ischaemic Stroke (Lancet.
  2001 358 702710)

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Characteristics of Trials Reviewed

• Randomised
• Double blind except IST
• Anticoagulants was started within 48hr of stroke
• Studies was analyzed individually

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Key Questions Reviewed

• Safety of Emergent Anticoagulation
• Prevention of Deep Vein Thrombosis
• Prevention of Early Recurrent Stroke
• Halting Neurological Worsening
• Reducing Mortality and Disability From Stroke
• Anticoagulation as an Adjunctive Therapy
• Current Status of Emergent Anticoagulation

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Safety of Emergent Anticoagulation
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Risk of Hemorrhagic Transformation with Emergent
Anticoagulants use

• NIHSS gt 15
• High dose anticoagulant is used
• No comparison of risk between different
  anticoagulants
• Non-neurologic hemorrhagic complication
• All the trials demonstrate an increased risk of
  hemorrhage with the administration of
  anticoagulants

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Prevention of Early Recurrent Stroke
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Halting Neurological Worsening
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Reducing Mortality and Disability From Stroke

• anticoagulants has not been associated with an
  increased rate of early mortality
• No significant decline in death or disability or
  increase in favorable outcomes with the
  administration of anticoagulants
• no net benefit from urgent anticoagulation

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Current Status of Emergent Anticoagulation

• Available trials do not provide any data to
  support the emergent administration of
  anticoagulants as a monotherapy for treating most
  patients with acute ischemic stroke
• No strong evidence to support the use of emergent
  anticoagulant therapy in the prevention of early
  recurrent stroke, in the arrest of neurological
  worsening, in the reduction of mortality, or in
  improving outcomes
• The studies show that anticoagulants are
  associated with an increase in the risk of
  serious bleeding complications, including
  symptomatic hemorrhagic transformation of the
  infarction

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Considering the Role of Heparin and
Low-Molecular-Weight Heparins in Acute Ischemic
Stroke

• Stroke. 33(7)1927-1933, July 2002

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Key Questions Discussed

• anticoagulation with parenteral unfractionated
  intravenous heparin (UFIH) and low-molecular-weigh
  t heparin (LMWH) for acute ischemic stroke
  remains an area of ongoing controversy
• lack of knowledge about a number of relevant
  variables such as the precise risk of early
  recurrent stroke (RS), the effect of UFIH and
  LMWH on recurrence risk, the natural history for
  the risk of secondary hemorrhagic conversion
  (SHC) and the effect of heparin on this risk, and
  the effects of UFIH and LMWH on improving stroke
  outcome

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Anticoagulants and antiplatelet agents in acute
ischemic stroke Report of the Joint Stroke
Guideline Development Committee of the American
Academy of Neurology and the American Stroke
Association (a Dividion of the American Heart
Association)

• Neurology July 2002

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Objectives

• Reviewed the published evidence relevant to the
  effects of anticoagulants and antiplatelet agents
  on acute ischemic stroke mortality, morbidity,
  and recurrence rates as well as associated
  ancillary benefits and risks of those treatments
  on the rates of deep vein thrombosis, pulmonary
  embolus, and cardiovascular complications

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Methods

• Reviewed by experienced neurologists appointed by
• Quality Standards Subcommittee (QSS) and the
  Therapeutics and Technology Assessment (TTA)
  Subcommittee of the American Academy of
  Neurology,
• The Stroke Council and Science Advisory and
  Coordinating Committee (SACC) of the American
  Heart Association (AHA).

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Methods

• The literature review was based on MEDLINE
  searches from 1966 through February 2001
• Treatments trial included unfractionated heparin,
  low molecular weight (LMW) heparin, heparinoids,
  aspirin, ticlopidine, clopidogrel, dipyridamole,
  hirudin, and glycoprotein IIb/IIIa antagonists
• a study had to be a controlled clinical trial
  that tested an anticoagulant or antiplatelet
  agent in patients with ischemic stroke
• the drug must have been given within 48 hours of
  symptom onset

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Results

• Of the 310 study reviewed, only 10 articles
  satisfied all inclusion criteria. Despite the
  apparently common use of anticoagulation for
  progressing stroke or vertebrobasilar stroke, we
  found no Class I or II evidence addressing these
  specific clinical situations.
• None of the included studies that fulfilled the
  prespecified inclusion criteria and addressed the
  reviews key questions examined the use of
  hirudin, dipyridamole, ticlopidine, or
  clopidogrel in the setting of acute ischemic
  stroke

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Recommendations 1

• Patients with acute ischemic stroke presenting
  within 48 hours of symptom onset should be given
  aspirin (160 to 325 mg/day) to reduce stroke
  mortality and decrease morbidity, provided
  contraindications such as allergy and
  gastrointestinal bleeding are absent, and the
  patient has or will not be treated with
  recombinant tissue-type plasminogen activator
  (Grade A). The data are insufficient at this time
  to recommend the use of any other platelet
  antiaggregant in the setting of acute ischemic
  stroke.

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Recommendations 2

• Subcutaneous unfractionated heparin, LMW
  heparins, and heparinoids may be considered for
  DVT prophylaxis in at-risk patients with acute
  ischemic stroke, recognizing that
  nonpharmacologic treatments for DVT prevention
  also exist (Grade A). A benefit in reducing the
  incidence of PE has not been demonstrated. The
  relative benefits of these agents must be weighed
  against the risk of systemic and intracerebral
  hemorrhage.

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Recommendations 3

• Although there is some evidence that fixed-dose,
  subcutaneous, unfractionated heparin reduces
  early recurrent ischemic stroke, this benefit is
  negated by a concomitant increase in the
  occurrence of hemorrhage. Therefore, use of
  subcutaneous unfractionated heparin is not
  recommended for decreasing the risk of death or
  stroke-related morbidity or for preventing early
  stroke recurrence (Grade A).

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Recommendations 4

• Dose-adjusted, unfractionated heparin is not
  recommended for reducing morbidity, mortality, or
  early recurrent stroke in patients with acute
  stroke (i.e., in the first 48 hours) because the
  evidence indicates it is not efficacious and may
  be associated with increased bleeding
  complications (Grade B).

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Recommendations 5

• High-dose LMW heparin/heparinoids have not been
  associated with either benefit or harm in
  reducing morbidity, mortality, or early recurrent
  stroke in patients with acute stroke and are,
  therefore, not recommended for these goals (Grade
  A).

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Recommendations 6

• IV, unfractionated heparin or high-dose LMW
  heparin/heparinoids are not recommended for any
  specific subgroup of patients with acute ischemic
  stroke that is based on any presumed stroke
  mechanism or location (e.g., cardioembolic, large
  vessel atherosclerotic, vertebrobasilar, or
  progressing stroke) because data are
  insufficient. Although the LMW heparin,
  dalteparin, at high doses may be efficacious in
  patients with atrial fibrillation, it is not more
  efficacious than aspirin in this setting. Because
  aspirin is easier to administer, it, rather than
  dalteparin, is recommended for the various stroke
  subgroups (Grade A).