This is the current release of the guideline.

This guideline updates a previous version: Albers GW, Amarenco P, Easton JD, Sacco RL, Teal P. Antithrombotic and thrombolytic therapy for ischemic stroke. Chest 2001 Jan;119(1 Suppl):300S-320S.

The rating scheme is defined at the end of the "Major Recommendations" field.

Acute Ischemic Stroke (AIS): Thrombolytic Therapy in Acute Stroke

Intravenous (IV) Tissue Plasminogen Activator (tPA) for AIS within 3 hours of Symptom Onset

1. For eligible patients (see inclusion and exclusion criteria listed below), the guideline developers recommend administration of IV tPA in a dose of 0.9 mg/kg (maximum 90 mg), with 10% of the total dose administered as an initial bolus, and the remainder infused over 60 min, provided that treatment is initiated within 3 hours of clearly defined symptom onset (Grade 1A).

   Underlying values and preferences: This recommendation assumes a relatively higher value on long-term functional improvement and a relatively lower value on minimizing the risk of intracranial hematomas (ICH) in the immediate peristroke period.

2. For patients with extensive (more than one third of the middle cerebral artery [MCA] territory) and clearly identifiable hypodensity on CT, the guideline developers recommend against thrombolytic therapy (Grade 1B).

IV tPA for AIS between 3 to 6 hours of Symptom Onset

1. For unselected patients with AIS of >3 hours but <6 hours, the guideline developers suggest clinicians not use IV tPA (Grade 2A).

   Underlying values and preferences: This recommendation assumes a relatively low value on small increases in long-term functional improvement, a relatively high value on avoiding acute ICH and death, and a relatively high degree of risk aversion.

IV Streptokinase for AIS between 0 and 6 hours of Symptom Onset

1. For patients with AIS, the guideline developers recommend against streptokinase (Grade 1A).

Intra-Arterial Thrombolysis for AIS

1. For patients with angiographically demonstrated middle cerebral artery (MCA) occlusion and no signs of major early infarction on the baseline CT scan, who can be treated within 6 hours of symptom onset, the guideline developers suggest use of intra-arterial thrombolytic therapy with tPA (Grade 2C).
2. For patients with acute basilar artery thrombosis and without major CT/magnetic resonance imaging (MRI) evidence of infarction, the guideline developers suggest intra-arterial thrombolysis with tPA (Grade 2C).

AIS: Patients Not Eligible for Thrombolysis

Anticoagulants for Altering Outcomes among Acute Stroke in Patients Not Eligible for Thrombolysis

1. For patients with AIS, the guideline developers suggest clinicians not use full-dose anticoagulation with IV, subcutaneous, or low molecular weight heparin or heparinoids (Grade 2B).

Antiplatelet Agents for Altering Outcomes in Acute Stroke in Patients Not Eligible for Thrombolysis

1. For patients with ischemic stroke who are not receiving thrombolysis, the guideline developers recommend early aspirin therapy, 160 to 325 mg/day (Grade 1A).

Antithrombotic Therapy for Prevention of Deep Vein Thrombosis (DVT) and Pulmonary Embolism (PE) in AIS

1. For acute stroke patients with restricted mobility, the guideline developers recommend prophylactic low-dose subcutaneous heparin or low molecular weight heparins or heparinoids (Grade 1A).
2. For patients who have contraindications to anticoagulants, the guideline developers recommend use of intermittent pneumatic compression devices or elastic stockings (Grade 1C).

DVT/PE Prophylaxis in Patients with ICH

Heparin for DVT/PE Prophylaxis in Patients with ICH

1. In patients with an acute ICH, the guideline developers recommend the initial use of intermittent pneumatic compression (Grade 1C+). In stable patients, the guideline developers suggest low-dose subcutaneous heparin may be initiated as soon as the second day after the onset of the hemorrhage (Grade 2C).

   Underlying values and preferences: The recommendation for subcutaneous heparin assumes a relatively low degree of risk aversion.

Stroke Prevention

Prevention of Cerebral Ischemic Events in Patients with Noncardioembolic Transient Ischemic Attack (TIA) or Stroke: Antiplatelet Drugs vs. Placebo or vs. an Alternative Antiplatelet Drug

1. In patients who have experienced a noncardioembolic stroke or TIA (i.e., atherothrombotic, lacunar, or cryptogenic), the guideline developers recommend treatment with an antiplatelet agent (Grade 1A). Aspirin at a dose of 50 to 325 mg daily (qd); the combination of aspirin, 25 mg, and extended-release dipyridamole, 200 mg twice a day (bid); or clopidogrel, 75 mg qd, are all acceptable options for initial therapy.
2. In patients receiving aspirin who are at moderate-to-high risk of bleeding complications, the guideline developers recommend using low doses of aspirin, 50 to 100 mg/day (Grade 1C+).
3. In patients who have experienced a noncardioembolic stroke or TIA, the guideline developers suggest use of the combination of aspirin and extended-release dipyridamole, 25/200 mg bid, over aspirin (Grade 2A), and clopidogrel over aspirin (Grade 2B).

   Underlying values and preferences: This recommendation to use the combination of aspirin and extended-release dipyridamole or clopidogrel over aspirin places a relatively high value on a small absolute risk reduction in stroke rates, and a relatively low value on minimizing drug expenditures.

4. For patients who are allergic to aspirin, the guideline developers recommend clopidogrel (Grade 1C+).

Prevention of Noncardioembolic Cerebral Ischemic Events: Oral Anticoagulants

1. For most patients with noncardioembolic stroke or TIA, the guideline developers recommend antiplatelet agents over oral anticoagulation (Grade 1A).
2. For patients with well-documented prothrombotic disorders, the guideline developers suggest oral anticoagulation over antiplatelet agents (Grade 2C).

Prevention of Cerebral Ischemic Events in Patients Undergoing Carotid Endarterectomy: Antiplatelet Agents

1. In patients undergoing carotid endarterectomy, the guideline developers recommend aspirin, 81 to 325 mg/d, prior to and following the procedure (Grade 1A).

Prevention of Cardioembolic Cerebral Ischemic Events

Patients with Stroke with Underlying Atrial Fibrillation: Anticoagulation

1. In patients with atrial fibrillation who have had a recent stroke or TIA, the guideline developers recommend long-term oral anticoagulation (target INR, 2.5; range, 2.0 to 3.0) [Grade 1A].

Patients with Stroke with Underlying Atrial Fibrillation: Antiplatelet Agents

1. For patients with cardioembolic stroke who have contraindications to anticoagulant therapy, the guideline developers recommend aspirin (Grade 1A).

Patients with Aortic Atheromata

1. In patients with stroke associated with aortic atherosclerotic lesions, the guideline developers recommend antiplatelet therapy over no therapy (Grade 1C+). For patients with cryptogenic stroke associated with mobile aortic arch thrombi, the guideline developers suggest either oral anticoagulation or antiplatelet agents (Grade 2C).

Patients with Patent Foramen Ovale (PFO)

1. In patients with cryptogenic ischemic stroke and a patent foramen ovale, the guideline developers recommend antiplatelet therapy over no therapy (Grade 1C+), and suggest antiplatelet agents over anticoagulation (Grade 2A).

Mitral Valve Strands and Prolapse

1. In patients with mitral valve strands or prolapse, who have a history of TIA or stroke, the guideline developers recommend antiplatelet therapy (Grade 1C+).

Cerebral Venous Sinus Thrombosis

Anticoagulation for Cerebral Venous Sinus Thrombosis

1. In patients with venous sinus thrombosis, the guideline developers recommend that clinicians use unfractionated heparin (Grade 1B) or low molecular weight heparin (Grade 1B) over no anticoagulant therapy during the acute phase, even in the presence of hemorrhagic infarction. In these patients, the guideline developers recommend oral anticoagulation for 3 to 6 months (target INR, 2.5; range, 2.0 to 3.0) [Grade 1C].

Definitions

*These situations include RCTs with both lack of blinding and subjective outcomes, where the risk of bias in measurement of outcomes is high, or RCTs with large loss to follow-up.

None provided

The type of supporting evidence is identified and graded for each recommendation (see "Major Recommendations").

Not applicable: The guideline was not adapted from another source.

2001 Jan (revised 2004 Sep)

American College of Chest Physicians - Medical Specialty Society

Funding was provided through an unrestricted educational grant by AstraZeneca LP, Aventis Pharmaceuticals, GlaxoSmithKline, Bristol-Myer Squibb/Sanofi-Synthelabo Partnership, and Organon Sanofi-Synthelabo LLC.

American College of Chest Physicians Consensus Panel on Antithrombotic and Thrombolytic Therapy

Primary Authors: Gregory W. Albers, MD (Chair); Pierre Amarenco, MD; J. Donald Easton, MD; Ralph L. Sacco, MD; Philip Teal, MD

Committee Co-Chairs: Jack Hirsh, MD, FCCP (Chair); Gregory W. Albers, MD; Gordon H. Guyatt, MD, MSc; Holger J. Schünemann, MD, MSc, PhD, FCCP

Participants: Giancarlo Agnelli, MD; Amin Al-Ahmad, MD; Pierre Amarenco, MD; Jack E. Ansell, MD; Shannon M. Bates, MD; Richard C. Becker, MD; Peter B. Berger, MD; David Bergqvist, MD, PhD, FRCS; Rebecca J. Beyth, MD, MSc; Stewart Brower, MLIS; Harry R. Buller, MD; Henry I. Bussey, PharmD, FCCP; Christopher P. Cannon, MD, FACC; Elizabeth A. Chalmers, MB, ChB, MD, MRCP(UK). FRCPath; Anthony K.C. Chan, MD; G. Patrick Clagett, MD; Barry Coller, MD; Clifford W. Colwell, MD; Deborah Cook, MD, MSc; James E. Dalen, MD, MPH, FCCP; J. Donald Easton, MD; Michael Ezekowitz, MD; Garret A. Fitzgerald, MD; William H. Geerts, MD, FCCP; Jeffrey S. Ginsberg, MD, FCCP; Alan S. Go, MD; Shaun D. Goodman, MD, FACC; Ian A. Greer, MD, FRCP, FRCOG; Andreas Greinacher, MD; Jeremy Grimshaw, MD, PhD; Cindy Grines, MD; Jonathan L. Halperin, MD; Robert A. Harrington, MD; John Heffner, MD, MPH; John A. Heit, MD; Judith S. Hochman, MD, FACC; Dieter Horstkotte, MD, FESC; Russell D. Hull, MBBS, MSc, FCCP; Elaine Hylek, MD; Thomas M. Hyers, MD, FCCP; Mark R. Jackson, MD; Alan Jacobson, MD; Roman Jaeschke, MD, MSc; Ajay Kakkar BSc, PhD; Clive Kearon, MD, PhD, FCCP; Matthew Kraay; Michael R. Lassen, MD; Mark N. Levine, MD, MSc; Alessandro Liberati, MD; Gregory YH Lip, MD, FESC, FACC; Warren J. Manning, MD; M. Patricia Massicotte, MD, MSc, FRCPC, MSc; Thomas W. Meade, MD; Venu Menon, MD, FACC; Alan D. Michelson, MD; Nancy Miller, RN; Paul Monagle, MBBS, MSc, MD, FRACP, FRCPA, FCCP; Heather Munger, MLS; Christopher M. O’Connor, MD; Martin O’Donnell, MD; E. Magnus Ohman, MD, FCCP; Carlo Patrono, MD; Stephen G. Pauker, MD; Graham F. Pineo, MD; Leon Poller, MD; Jeffrey J. Popma, MD; Martin H. Prins, MD; Robert Raschke, MD, MS; Gary Raskob, PhD; Joel G. Ray, MD, MSc; Gerald Roth, MD; Ralph L. Sacco, MD; Deeb N. Salem, MD, FCCP; Meyer M. Samama, MD; Andrew Schafer; Sam Schulman, MD, PhD; Daniel Singer, MD; Michael Sobel, MD; Paul D. Stein, MD, FCCP; Marco Tangelder, MD; Victor F. Tapson, MD, FCCP; Philip Teal, MD; Raymond Verhaeghe, MD; David A. Vorchheimer, MD; Theodore E. Warkentin, MD; Jeffrey Weitz, MD; Robert G. Wilcox, MD

Dr. Albers has received research support and honoraria as a consultant from AstraZeneca, Bristol- Myers Squibb, Boehringer Ingelheim, Genentech and Sanofi-Arganon.

Dr. Easton has received honoraria for his participation on advisory boards or as a speaker at educational events from Boehringer Ingelheim, Bristol- Myers Squibb, and Sanofi-Synthelabo.

Dr. Sacco has received research funding from GlaxoSmithKline and Pfizer, and has received honoraria for his participation as a consultant on advisory boards, data and safety monitoring boards and/or as a speaker at educational events from Boehringer Ingelheim, sanofi-Synthelabo, Bristol-Myers Squibb, Pfizer, AstraZeneca, GlaxoSmithKline, and Texas Biotechnology.

Dr. Teal has received honoraria for participation on advisory boards and/or as a speaker at medical education events supported by Boehringer-Ingelheim, Sanofi-Synthelabo and Bayer, Servier, Aventis, PAION, AstraZeneca, and Hoffman-LaRoche. He has served on research steering committees for clinical trials conducted by Boehinger-Ingelheim, Bayer, ONO Pharmaceuticals and Pfizer and Eli-Lilly, EKOS, GlaxoSmithKline, and Yamaguichi.

This is the current release of the guideline.

This guideline updates a previous version: Albers GW, Amarenco P, Easton JD, Sacco RL, Teal P. Antithrombotic and thrombolytic therapy for ischemic stroke. Chest 2001 Jan;119(1 Suppl):300S-320S.

This summary was completed by ECRI on July 30, 2001. The information was verified by the guideline developer on September 27, 2001. This NGC summary was updated by ECRI on December 9, 2004. The updated information was verified by the guideline developer on January 12, 2005. This summary was updated by ECRI Institute on June 22, 2007 following the U.S. Food and Drug Administration (FDA) advisory on heparin sodium injection. This summary was updated by ECRI Institute on March 14, 2008 following the updated FDA advisory on heparin sodium injection.

This NGC summary is based on the original guideline, which is subject to the guideline developer's copyright restrictions.