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Antithrombotic Therapy and Prevention of Thrombosis, 9th Ed: American College of Chest Physician Evidence-Based Clinical Practice Guidelines Online Only Articles |

Antithrombotic and Thrombolytic Therapy for Ischemic StrokeAntithrombotic Therapy for Ischemic Stroke: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines FREE TO VIEW

Maarten G. Lansberg, MD, PhD; Martin J. O’Donnell, PhD; Pooja Khatri, MD; Eddy S. Lang, MDCM; Mai N. Nguyen-Huynh, MD; Neil E. Schwartz, MD, PhD; Frank A. Sonnenberg, MD; Sam Schulman, MD, PhD; Per Olav Vandvik, MD, PhD; Frederick A. Spencer, MD; Pablo Alonso-Coello, MD, PhD; Gordon H. Guyatt, MD, FCCP; Elie A. Akl, MD, MPH, PhD
Author and Funding Information

Funding/Support: The Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines received support from the National Heart, Lung, and Blood Institute [R13 HL104758]and Bayer Schering Pharma AG. Support in the form of educational grants were also provided by Bristol-Myers Squibb; Pfizer, Inc; Canyon Pharmaceuticals; and sanofi-aventis US.

Funding/Support: The Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines received support from the National Heart, Lung, and Blood Institute [R13 HL104758]and Bayer Schering Pharma AG. Support in the form of educational grants were also provided by Bristol-Myers Squibb; Pfizer, Inc; Canyon Pharmaceuticals; and sanofi-aventis US.

Disclaimer: American College of Chest Physician guidelines are intended for general information only, are not medical advice, and do not replace professional medical care and physician advice, which always should be sought for any medical condition. The complete disclaimer for this guideline can be accessed at http://chestjournal.chestpubs.org/content/141/2_suppl/1S.

Disclaimer: American College of Chest Physician guidelines are intended for general information only, are not medical advice, and do not replace professional medical care and physician advice, which always should be sought for any medical condition. The complete disclaimer for this guideline can be accessed at http://chestjournal.chestpubs.org/content/141/2_suppl/1S.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (http://www.chestpubs.org/site/misc/reprints.xhtml).

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (http://www.chestpubs.org/site/misc/reprints.xhtml).


Chest. 2012;141(2_suppl):e601S-e636S. doi:10.1378/chest.11-2302
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Objectives:  This article provides recommendations on the use of antithrombotic therapy in patients with stroke or transient ischemic attack (TIA).

Methods:  We generated treatment recommendations (Grade 1) and suggestions (Grade 2) based on high (A), moderate (B), and low (C) quality evidence.

Results:  In patients with acute ischemic stroke, we recommend IV recombinant tissue plasminogen activator (r-tPA) if treatment can be initiated within 3 h (Grade 1A) or 4.5 h (Grade 2C) of symptom onset; we suggest intraarterial r-tPA in patients ineligible for IV tPA if treatment can be initiated within 6 h (Grade 2C); we suggest against the use of mechanical thrombectomy (Grade 2C) although carefully selected patients may choose this intervention; and we recommend early aspirin therapy at a dose of 160 to 325 mg (Grade 1A). In patients with acute stroke and restricted mobility, we suggest the use of prophylactic-dose heparin or intermittent pneumatic compression devices (Grade 2B) and suggest against the use of elastic compression stockings (Grade 2B). In patients with a history of noncardioembolic ischemic stroke or TIA, we recommend long-term treatment with aspirin (75-100 mg once daily), clopidogrel (75 mg once daily), aspirin/extended release dipyridamole (25 mg/200 mg bid), or cilostazol (100 mg bid) over no antiplatelet therapy (Grade 1A), oral anticoagulants (Grade 1B), the combination of clopidogrel plus aspirin (Grade 1B), or triflusal (Grade 2B). Of the recommended antiplatelet regimens, we suggest clopidogrel or aspirin/extended-release dipyridamole over aspirin (Grade 2B) or cilostazol (Grade 2C). In patients with a history of stroke or TIA and atrial fibrillation we recommend oral anticoagulation over no antithrombotic therapy, aspirin, and combination therapy with aspirin and clopidogrel (Grade 1B).

Conclusions:  These recommendations can help clinicians make evidence-based treatment decisions with their patients who have had strokes.

From the Stanford Stroke Center (Drs Lansberg and Schwartz), Department of Neurology and Neurological Sciences, Stanford University, Palo Alto, CA; the HRB-Clinical Research Faculty (Dr O’Donnell), National University of Ireland Galway, Galway, Ireland; the Department of Neurology (Dr Khatri), University of Cincinnati, Cincinnati, OH; the University of Calgary (Dr Lang), Calgary, AB, Canada; the Department of Neurology (Dr Nguyen-Huynh), University of California, San Francisco, CA; the Division of General Internal Medicine (Dr Sonnenberg), UMDNJ/Robert Wood Johnson Medical School, New Brunswick, NJ; the Department of Medicine (Drs Schulman and Guyatt), McMaster University, ON, Canada; the Norwegian Knowledge Centre for the Health Services (Dr Vandvik), Oslo, Norway; St. Joseph’s Healthcare (Dr Spencer), Hamilton, ON, Canada; the Iberoamerican Cochrane Centre (Dr Alonso-Coello), CIBERESP-IIB Sant Pau, Barcelona, Spain; the State University of New York at Buffalo (Dr Akl), Buffalo, NY; and the Department of Clinical Epidemiology and Biostatistics (Drs Akl and Guyatt), McMaster University, Hamilton, ON, Canada.

Correspondence to: Elie A. Akl, MD, MPH, PhD, State University of New York at Buffalo, ECMC, DK Miller bldg C216, 462 Grider St, Buffalo, NY 14228; e-mail: elieakl@buffalo.edu

Author contributions: As Topic Editor, Dr Akl oversaw the development of this article, including the data analysis and subsequent development of the recommendations contained herein.Dr Lansberg: contributed as Deputy Editor.

Dr O’Donnell: contributed as a panelist.

Dr Khatri: contributed as a panelist.

Dr Lang: contributed as a panelist.

Dr Nguyen-Huynh: contributed as a panelist.

Dr Schwartz: contributed as frontline clinician.

Dr Sonnenberg: contributed as a resource consultant.

Dr Schulman: contributed as a panelist.

Dr Vandvik: contributed as a panelist.

Dr Spencer: contributed as a panelist.

Dr Alonso-Coello: contributed as a panelist.

Dr Guyatt: contributed as a panelist.

Dr Akl: contributed as Topic Editor.

Financial/nonfinancial disclosures: The authors of this guideline provided detailed conflict of interest information related to each individual recommendation made in this article. A grid of these disclosures is available online at http://chestjournal.chestpubs.org/content/141/2_suppl/e601S/suppl/DC1. In summary, the authors have reported to CHEST the following conflicts of interest: Dr O'Donnell has received university grants; received grants, speaking fees, and travel accommodations from Boehringer Ingelheim, and has received speaking fees from sanofi-aventis. Dr Khatri will receive funding from Penumbra, Inc as THERAPY Trial Neurology PI; received research support for third-party survey services and travel support for a 1-day summit in Chicago from Genentech, Inc to study RISS; participated in a one-time advisory board for Otsuka Pharmaceuticals regarding cilostazol; and provided expert witnessing regarding cases related to stroke treatment. Drs Lansberg and Schwartz have served as expert witnesses in cases related to stroke. Dr Nguyen-Huynh received a research grant from Concentric Medical. Dr Lang is a member of the GRADE Working Group. Dr Guyatt is co-chair of the GRADE Working Group, and the following authors have been prominent contributors to the groups work: Drs Vandvik, Alonso-Coello, and Akl. Drs Sonnenberg, Spencer, and Schulman have reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Role of sponsors: The sponsors played no role in the development of these guidelines. Sponsoring organizations cannot recommend panelists or topics, nor are they allowed prepublication access to the manuscripts and recommendations. Guideline panel members, including the chair, and members of the Health & Science Policy Committee are blinded to the funding sources. Further details on the Conflict of Interest Policy are available online at http://chestnet.org.

Other contributions: We thank the writing groups of the article on antithrombotic and thrombolytic therapy for ischemic stroke in previous iterations of the ACCP evidence-based clinical practice guidelines for providing the framework for the current article; Mark Eckman, MD, for his contribution to the section that deals with antithrombotic therapy for stroke prevention following intracerebral hemorrhage; Aman Rajpal, MD, for his help with reviewing the proofs; and Peter Pellionisz for his contributions in editing the online tables.

Endorsements: This guideline is endorsed by the American Association for Clinical Chemistry, the American College of Clinical Pharmacy, the American Society of Health-System Pharmacists, the American Society of Hematology, and the International Society of Thrombosis and Hematosis.

Additional information: The supplement Tables can be found in the Online Data Supplement at http://chestjournal.chestpubs.org/content/141/2_suppl/e601S/suppl/DC1.

Funding/Support: The Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines received support from the National Heart, Lung, and Blood Institute [R13 HL104758]and Bayer Schering Pharma AG. Support in the form of educational grants were also provided by Bristol-Myers Squibb; Pfizer, Inc; Canyon Pharmaceuticals; and sanofi-aventis US.

Disclaimer: American College of Chest Physician guidelines are intended for general information only, are not medical advice, and do not replace professional medical care and physician advice, which always should be sought for any medical condition. The complete disclaimer for this guideline can be accessed at http://chestjournal.chestpubs.org/content/141/2_suppl/1S.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (http://www.chestpubs.org/site/misc/reprints.xhtml).

Note on Shaded Text: Throughout this guideline, shading is used within the summary of recommendations sections to indicate recommendations that are newly added or have been changed since the publication of Antithrombotic and Thrombolytic Therapy: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Recommendations that remain unchanged are not shaded.

2.1.1. In patients with acute ischemic stroke in whom treatment can be initiated within 3 h of symptom onset, we recommend IV recombinant tissue plasminogen activator (r-tPA) over no IV r-tPA (Grade 1A).

2.1.2. In patients with acute ischemic stroke in whom treatment can be initiated within 4.5 h but not within 3 h of symptom onset, we suggest IV r-tPA over no IV r-tPA (Grade 2C).

2.1.3. In patients with acute ischemic stroke in whom treatment cannot be initiated within 4.5 h of symptom onset, we recommend against IV r-tPA (Grade 1B).

2.2.1. In patients with acute ischemic stroke due to proximal cerebral artery occlusions who do not meet eligibility criteria for treatment with IV r-tPA, we suggest intraarterial (IA) r-tPA initiated within 6 h of symptom onset over no IA r-tPA (Grade 2C).

2.2.2. In patients with acute ischemic stroke we suggest IV r-tPA over the combination IV/IA r-tPA (Grade 2C).

Remarks: Carefully selected patients who value the uncertain benefits of combination IV/IA thrombolysis higher than the associated risks may choose this intervention. Patients who prefer to avoid risk in the setting of uncertain benefits are more likely to choose IV r-tPA alone.

2.3. In patients with acute ischemic stroke, we suggest against the use of mechanical thrombectomy (Grade 2C).

Remarks: Carefully selected patients who value the uncertain benefits of mechanical thrombectomy higher than the associated risks may choose this intervention.

2.4. In patients with acute ischemic stroke or transient ischemic attack (TIA), we recommend early (within 48 h) aspirin therapy at a dose of 160 to 325 mg over no aspirin therapy (Grade 1A).

2.5. In patients with acute ischemic stroke or TIA, we recommend early (within 48 h) aspirin therapy with an initial dose of 160 to 325 mg over therapeutic parenteral anticoagulation (Grade 1A).

3.1.1. In patients with acute ischemic stroke and restricted mobility, we suggest prophylactic-dose subcutaneous heparin (unfractionated heparin [UFH] or low-molecular-weight heparin [LMWH]) or intermittent pneumatic compression devices over no prophylaxis (Grade 2B).

3.1.2. In patients with acute ischemic stroke and restricted mobility, we suggest prophylactic-dose LMWH over prophylactic-dose UFH (Grade 2B).

3.1.3. In patients with acute stroke and restricted mobility, we suggest against elastic compression stockings (Grade 2B).

Remarks: Pharmacologic and mechanical prophylaxis should be initiated as early as possible and should be continued throughout the hospital stay or until the patient has regained mobility. Mechanical devices should be temporarily removed as often as needed to allow for early mobilization and screening for skin complications.

Combining pharmacologic therapy with intermittent pneumatic compression devices may yield additional benefit in prevention of VTEs compared with either method used alone.