This is the current release of the guideline.

This guideline updates a previous version: Cairns JA, Theroux P, Lewis HD Jr, Ezekowitz M, Meade TW. Antithrombotic agents in coronary artery disease. Chest 2001 Jan;119(1 Suppl):228S-252S.

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

Acute Management of Non-ST-Elevation Acute Coronary Syndromes (NSTE ACS)

Antiplatelet Therapies

Aspirin

1. For all patients presenting with an NSTE ACS, without a clear allergy to aspirin, the guideline developers recommend immediate aspirin, 75 to 325 mg orally (PO), and then daily oral aspirin, 75 to 162 mg (Grade 1A).

Thienopyridines

1. For all NSTE ACS patients with an aspirin allergy, the guideline developers recommend immediate treatment with clopidogrel, 300 mg oral bolus, followed by 75 mg/day indefinitely (Grade 1A).
2. In all NSTE ACS patients in whom diagnostic catheterization will be delayed or when coronary bypass surgery will not occur until >5 days following coronary angiography, the guideline developers recommend clopidogrel be administered immediately as bolus therapy (300 mg), followed by 75 mg/day for 9 to 12 months in addition to aspirin (Grade 1A).

   Underlying values and preferences: This recommendation places a relatively high value on avoiding myocardial infarction (MI) and a relatively low value on avoiding major bleeding.

3. In NSTE ACS patients in whom angiography will take place rapidly (<24 hours), the guideline developers suggest beginning clopidogrel after the coronary anatomy has been determined (Grade 2A).

   Underlying values and preferences: This recommendation places a relatively high value on avoiding serious bleeding balanced against a low absolute benefit of clopidogrel in the first 24 hours of treatment.

4. For patients who have received clopidogrel and are scheduled for coronary bypass surgery, the guideline developers recommend discontinuing clopidogrel for 5 days prior to the scheduled surgery (Grade 2A).

Glycoprotein (GP) IIb/IIIa Inhibitors

1. In moderate- to high-risk patients presenting with NSTE ACS, the guideline developers recommend either eptifibatide or tirofiban for initial (early) treatment in addition to treatment with aspirin and heparin (Grade 1A). In these moderate- to high-risk patients who are also receiving clopidogrel, the guideline developers recommend eptifibatide or tirofiban as additional initial treatment (Grade 2A).
2. For patients presenting with NSTE ACS, the guideline developers recommend against abciximab as initial treatment except when the coronary anatomy is known and percutaneous coronary intervention (PCI) planned within 24 hours (Grade 1A).

Antithrombin Therapies

Unfractionated Heparin (UFH)

1. For patients presenting with NSTE ACS, the guideline developers recommend UFH over no heparin therapy for short-term use with antiplatelet therapies (Grade 1A). The guideline developers recommend weight-based dosing of UFH and maintenance of the activated partial thromboplastin time (aPTT) between 50 s and 75 s (Grade 1C+).

Low-Molecular-Weight Heparin (LMWH)

1. For the acute treatment of patients with NSTE ACS, the guideline developers recommend LMWHs over UFH (Grade 1B).
2. The guideline developers recommend against routine monitoring of the anticoagulant effect of the LMWHs (Grade 1C).
3. The guideline developers suggest continuing LMWHs during PCI treatment of the NSTE ACS patient when it has been started as the upstream anticoagulant (Grade 2C).
4. For patients receiving GP IIb/IIIa inhibitors as upstream treatment of NSTE ACS, the guideline developers suggest LMWH over UFH as the anticoagulant of choice (Grade 2B).

Direct Thrombin Inhibitors (DTIs)

1. In patients presenting with NSTE ACS, the guideline developers recommend against DTIs as routine initial antithrombin therapy (Grade 1B).

   Underlying values and preferences: This recommendation acknowledges the limitations of the individual trials of DTIs in NTSE ACS as well as the complexities of using the DTIs compared with either UFH or LMWH.

Post MI and Post ACS

Antiplatelet Therapies

In patients with ACSs with and without ST-segment elevation:

1. The guideline developers recommend aspirin at initial doses from 160 to 325 mg, and then indefinite therapy, 75 to 162 mg/day (Grade 1A).
2. For patients with a history of aspirin-induced bleeding or with risk factors for bleeding, the guideline developers recommend lower doses (<100 mg) of aspirin (Grade 1C+).
3. For patients in whom aspirin is contraindicated or not tolerated, the guideline developers recommend clopidogrel for long-term administration, 75 mg/day (Grade 1A).

Comparisons of Antiplatelet and Anticoagulant Therapy and/or Combinations of Aspirin and Warfarin Trials

1. In most health-care settings, for moderate- and low-risk patients with MI, the guideline developers recommend aspirin alone over oral vitamin K antagonists (VKAs) plus aspirin (Grade 2B).

   Underlying values and preferences: This recommendation places a relatively low value on prevention of thromboembolism and a relatively high value on avoiding the inconvenience, expense, and bleeding associated with VKA therapy.

2. In health-care settings in which meticulous international normalized ratio (INR) monitoring is standard and routinely accessible, for both high- and low-risk patients after MI, the guideline developers recommend long-term (up to 4 years) high-intensity oral VKAs (target INR, 3.5; range 3.0 to 4.0) without concomitant aspirin or moderate-intensity oral VKAs (target INR, 2.5; range 2.0 to 3.0) with aspirin (both Grade 2B).
3. For high-risk patients with MI, including those with a large anterior MI, those with significant heart failure, those with intracardiac thrombus visible on echocardiography, and those with a history of a thromboembolic event, the guideline developers suggest the combined use of moderate-intensity (INR, 2.0 to 3.0) oral VKAs plus low-dose aspirin (<100 mg/day) for 3 months after the MI (Grade 2A).

Chronic, Stable Coronary Artery Disease (CAD)

Antiplatelet Agents

1. For all patients with chronic stable CAD, the guideline developers recommend the administration of aspirin, 75 to 162 mg po (Grade 1A). The guideline developers suggest that aspirin be continued indefinitely (Grade 2C).
2. For patients with stable chronic coronary disease with a risk profile indicating a high likelihood of development of acute MI (AMI), the guideline developers suggest long-term therapy with clopidogrel in addition to aspirin (Grade 2C).

VKAs

1. For patients with chronic CAD without prior MI, the guideline developers suggest clinicians not use long-term oral VKAs (Grade 2C).

Congestive Heart Failure (CHF) With and Without CAD

VKA, Aspirin

1. In patients with CHF due to a nonischemic etiology, the guideline developers recommend against routine use of aspirin or oral VKAs (Grade 1B).
2. The guideline developers recommend that when otherwise indicated, patients receive aspirin whether or not they are receiving angiotensin-converting enzyme inhibitors (ACEIs) (Grade 1C+).

Primary Prevention

Aspirin, VKA, or Both

1. For patients with at least moderate risk for a coronary event (based on age and cardiac risk factor profile with a 10-year risk of a cardiac event of >10%), the guideline developers recommend aspirin, 75 to 162 mg/day, over either no antithrombotic therapy or VKAs (Grade 2A).
2. For patients at particularly high risk of events in whom INR can be monitored without difficulty, the guideline developers suggest low-dose VKAs with a target INR of approximately 1.5 (Grade 2A).

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: Robert A. Harrington, MD; Richard C. Becker, MD, FCCP; Michael Ezekowitz, MD; Thomas W. Meade, DM, FCCP; Christopher M. O’Connor, MD; David A. Vorchheimer, MD; Gordon H. Guyatt, MD, FCCP

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. Robert Harrington has received research grants through the Duke Clinical Research Institute from Aventis, AstraZeneca, Millennium, Schering, Merck, Lilly, Centocor, Roche, The Medicines Company, BMS, Sanofi, Glaxo, Daiichi.

Dr. Ezekowitz has received research funding from AstraZeneca/B.I. and is a consultant for AstraZeneca, B.I. Eli Lilly, Pfizer, Aventis, Glaxo, and Wyeth.

Dr. Meade has received payment as a member of ISEAC, the Independent Scientific and Ethics Advisory Committee to IMS Healthcare, a general practice database used for research and has received honoraria from Bayer.

Dr. Vorchheimer has received research funding from AstraZeneca, Sanofi, and has received honoraria for his participation on advisory boards and/or as a speaker at educational events sponsored by Millennium Pharmaceuticals, and Sanofi.

Dr. Guyatt has received research support from Abbott Laboratories Limited, AstraZeneca AB, Eli Lilly Canada, Leo Pharma, and Aventis.

This is the current release of the guideline.

This guideline updates a previous version: Cairns JA, Theroux P, Lewis HD Jr, Ezekowitz M, Meade TW. Antithrombotic agents in coronary artery disease. Chest 2001 Jan;119(1 Suppl):228S-252S.

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 on March 6, 2007 following the U.S. Food and Drug Administration (FDA) advisory on Coumadin (warfarin sodium). 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 July 12, 2007 following the U.S. Food and Drug Administration (FDA) advisory on Troponin-1 Immunoassay. This summary was updated by ECRI Institute on September 7, 2007 following the revised U.S. Food and Drug Administration (FDA) advisory on Coumadin (warfarin). 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.