ACCP 8冠心病一二级预防原文

DOI 10.1378/chest.08-0685 2008;133;776S-814SChest Guyatt, Daniel B. Mark and Robert A. Harrington Ezekowitz, Christopher M. O'Connor, David A. Vorchheimer, Gordon H. Richard C. Becker, Thomas W. Meade, Peter B. Berger, Michael Clinical Practice Guidelines (8th Edition) Evidence-BasedCollege of Chest Physicians : American*Coronary Artery Disease The Primary and Secondary Prevention of http://chestjournal.chestpubs.org/content/133/6_suppl/776S.full.html services can be found online on the World Wide Web at: The online version of this article, along with updated information and ISSN:0012-3692 )http://chestjournal.chestpubs.org/site/misc/reprints.xhtml( written permission of the copyright holder. this article or PDF may be reproduced or distributed without the prior Dundee Road, Northbrook, IL 60062. All rights reserved. No part of Copyright2008by the American College of Chest Physicians, 3300 Physicians. It has been published monthly since 1935. is the official journal of the American College of ChestChest © 2008 American College of Chest Physicians by guest on July 23, 2011chestjournal.chestpubs.orgDownloaded from The Primary and Secondary Prevention of Coronary Artery Disease* American College of Chest Physicians Evidence- Based Clinical Practice Guidelines (8th Edition) Richard C. Becker, MD; Thomas W. Meade, DM, FCCP; Peter B. Berger, MD; Michael Ezekowitz, MD; Christopher M. O’Connor, MD; David A. Vorchheimer, MD; Gordon H. Guyatt, MD, FCCP; Daniel B. Mark, MD; and Robert A. Harrington, MD, FCCP The following chapter devoted to antithrombotic therapy for chronic coronary artery disease (CAD) is part of the Antithrombotic and Thrombolytic Therapy: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Grade 1 recommendations are strong and indicate that the benefits do or do not outweigh risks, burden, and costs. Grade 2 suggests that individual patient values may lead to different choices (for a full understanding of the grading see the “Grades of Recommendation” chapter by Guyatt et al in this supplement, CHEST 2008; 133[suppl]: 123S–131S). Among the key recommendations in this chapter are the following: for patients with non–ST-segment elevation (NSTE)-acute coronary syndrome (ACS) we recommend daily oral aspirin (75–100 mg) [Grade 1A]. For patients with an aspirin allergy, we recommend clopidogrel, 75 mg/d (Grade 1A). For patients who have received clopidogrel and are scheduled for coronary bypass surgery, we suggest discontinuing clopidogrel for 5 days prior to the scheduled surgery (Grade 2A). For patients after myocardial infarction, after ACS, and those with stable CAD and patients after percutaneous coronary intervention (PCI), we recommend daily aspirin (75–100 mg) as indefinite therapy (Grade 1A). We recommend clopidogrel in combination with aspirin for patients experiencing ST-segment elevation (STE) and NSTE-ACS (Grade 1A). For patients with contraindications to aspirin, we recommend clopidogrel as monotherapy (Grade 1A). For long-term treatment after PCI in patients who receive antithrombotic agents such as clopidogrel or warfarin, we recommend aspirin (75 to 100 mg/d) [Grade 1B]. For patients who undergo bare metal stent placement, we recommend the combination of aspirin and clopidogrel for at least 4 weeks (Grade 1A). We recommend that patients receiving drug-eluting stents (DES) receive aspirin (325 mg/d for 3 months followed by 75–100 mg/d) and clopidogrel 75 mg/d for a minimum of 12 months (Grade 2B). For primary prevention in patients with moderate risk for a coronary event, we recommend aspirin, 75–100 mg/d, over either no antithrombotic therapy or vitamin K antagonist (Grade 1A). (CHEST 2008; 133:776S–814S) Key words: atherosclerosis; primary prevention; secondary prevention; thrombosis Abbreviations: ACEI � angiotensin-converting enzyme inhibitor; ACS � acute coronary syndrome; BMS � bare metal stent; CABG � coronary artery bypass grafting; CAD � coronary artery disease; CHD � coronary heart disease; CHF � congestive heart failure; CI � confidence interval; DES � drug-eluting stent; IHD � ischemic heart disease; IMA � internal mammary artery; INR� international normalized ratio; LMWH� low-molecular-weight heparin; MI�myocardial infarction; MIDCAB�minimally invasive direct coronary artery bypass; NNH� number needed to harm; NNT � number needed to treat; NS � not significant; NSAID � nonsteroidal anti-inflammatory drug; NSTE � non–ST-segment elevation; OPCAB � off-pump coronary artery bypass; OR � odds ratio; PCI � percutaneous coronary intervention; PTCA � percutaneous transluminal coronary angioplasty; QALY � quality of life year; RCT � randomized clinical trial; RR � relative risk; RRR � relative risk reduction; SC � subcutaneous; SK � streptokinase; STE � ST-segment elevation; TE � thromboembolism; TIA � transient ischemic attack; UFH � unfractionated heparin; VKA � vitamin K antagonist Supplement ANTITHROMBOTIC AND THROMBOLYTIC THERAPY 8TH ED: ACCP GUIDELINES 776S Antithrombotic and Thrombolytic Therapy 8th Ed: ACCP Guidelines © 2008 American College of Chest Physicians by guest on July 23, 2011chestjournal.chestpubs.orgDownloaded from Summary of Recommendations 1.1.1. For patients with ACS with and without STE, we recommend aspirin initially at a dose of 75–162 mg and then indefinitely at a dose of 75–100 mg/d (Grade 1A). 1.1.2. For patients with STE ACS, with or without fibrinolytic therapy, we recommend clopidogrel as a 300-mg oral loading dose for patients < 75 years of age and 75-mg starting dose for those > 75 years of age, and continued at a daily dose of 75 mg for 2–4 weeks (Grade 1A). We suggest continuing clopidogrel for up to 12 months fol- lowing hospital discharge (Grade 2B). 1.1.3. For patients with NSTE ACS, we recom- mend combination therapy with aspirin (75–100 mg/d) and clopidogrel (75 mg/d) for 12 months (Grade 1A). 1.1.4. For patients in whom aspirin is contrain- dicated or not tolerated, we recommend clopi- dogrel monotherapy (75 mg/d) [Grade 1A]. 1.1.5. For patients with symptomatic CAD, we suggest aspirin (75–100 mg/d) in combination with clopidogrel (75 mg/d) [Grade 2B]. Values and preferences: This recommendation places a high value on the probable small reduction in arterial vascular risk consequent on adding clopi- dogrel to aspirin and a low value on avoiding the additional bleeding and high cost associated with clopidogrel. 2.1. For most patients (all except the high-risk group described in Recommendation 2.2 be- low) in most health-care settings, following ACS, we recommend aspirin alone (75–100 mg daily) over oral vitamin K antagonists (VKAs) alone or in combination with aspirin (Grade 1B). Values and preferences: This Recommendation places a relatively low value on prevention of thromboembo- lism, and a relatively high value on avoiding the incon- venience, expense, and bleeding risk associated with VKA therapy. 2.1.1. For most patients after MI, in health-care settings in which meticulous international nor- malized ratio (INR) monitoring and highly skilled VKA dose titration are expected and widely accessible, we suggest long-term (up to 4 years) high-intensity oral VKA (target INR, 3.5; range, 3.0 to 4.0) without concomitant aspirin or moderate-intensity oral VKA (target INR, 2.5; range 2.0 to 3.0) with aspirin (< 100 mg/d) over aspirin alone (both Grade 2B). 2.2. For high-risk patients with MI, including those with a large anterior MI, those with signif- icant heart failure, those with intracardiac throm- bus visible on transthoracic echocardiography, those with atrial fibrillation and those with a history of a thromboembolic event, we suggest the combined use of moderate-intensity (INR, 2.0 to 3.0) oral VKA plus low-dose aspirin (< 100 mg/d) for at least 3 months after the MI (Grade 2A). 2.4. For long-term treatment of patients after per- cutaneous coronary intervention (PCI), we recom- mend aspirin at a dose of 75–100 mg/d (Grade 1A). 2.4.1. For patients undergoing PCI with bare metal stent (BMS) placement, we recommend aspirin (75– 100mg/d) plus clopidogrel over aspirin alone (Grade 1A). 2.4.1.1. For patients undergoing PCI with BMS placement following ACS, we recommend 12 months of aspirin (75–100 mg/d) plus clopidogrel (75 mg/d) over aspirin alone (Grade 1A). 2.4.1.2. For patients undergoing PCI with a DES, we recommend aspirin (75–100 mg/d) plus clopi- dogrel (75mg/d for at least 12months) [Grade 1A for 3 to 4 months; Grade 1B for 4 to 12 months]. Beyond 1 year, we suggest continued treatment with aspirin plus clopidogrel indefinitely if no bleeding or other tolerability issues (Grade 2C). 2.4.2. For patients undergoing stent placementwith a strong concomitant indication forVKA,we suggest triple antithrombotic therapy (Grade 2C). We sug- gest 4 weeks of clopidogrel following BMS and 1 year following DES (Grade 2C). Values and preferences: This recommendation places a high value on the prevention of thromboembolism, in- cluding stent thrombosis, and a lower value onminimizing bleeding risk. For recommendations on the use of antiplatelet agents in other patient populations with atrial fibril- lation, see the “Antithrombotic Therapy in Atrial Fibrillation” chapter. *From Duke Clinical Research Institute (Dr. Becker), Duke University Medical Center, Durham, NC; Non Comm Disease Epidemiology (Dr. Meade), London School of Hygiene Tropical, London, UK; Geisinger Center for Health Research (Dr. Berger), Danville, PA; Lankenau Institute for Medical Research (Dr. Ezekowitz), Wynnewood, PA; Duke University Medical Center (Dr. O’Connor), Division of Cardiology, Durham, NC; Mount Sinai Medical Center (Dr. Vorchheimer), New York, NY; McMaster University Health Sciences Centre (Dr. Guyatt), Hamilton, ON, Canada; Duke University Medical School (Dr. Mark), Durham, NC; and Duke Clinical Research Institute (Dr. Harrington), Duke University Medical Center, Durham, NC. Manuscript accepted December 20, 2007. Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal. org/misc/reprints.shtml). Correspondence to: Richard C. Becker, MD, Professor of Medi- cine, Director, Duke Cardiovascular Thrombosis Center, Duke Clinical Research Institute, 2400 Pratt St, Durham, NC 27705; e-mail: becke021@mc.duke.edu DOI: 10.1378/chest.08-0685 www.chestjournal.org CHEST / 133 / 6 / JUNE, 2008 SUPPLEMENT 777S © 2008 American College of Chest Physicians by guest on July 23, 2011chestjournal.chestpubs.orgDownloaded from 2.5. For patients after stent placement, we sug- gest clopidogrel (Grade 1A) or ticlopidine (Grade 2B) over cilostazol. We recommend clopidogrel over ticlopidine (Grade 1A). 2.5.1. For aspirin-intolerant patients undergo- ing PCI, we recommend use of a thienopyridine derivative rather than dipyridamole (Grade 1B). 2.6. For patients who undergo PCI with no other indication for VKA, we recommend against VKA (Grade 1A). 3.1. In patients with congestive heart failure due to a nonischemic etiology, we recommend against routine use of aspirin or oral VKA (Grade 1B). 4.1.5. For all patients with CAD undergoing coronary artery bypass grafting (CABG), we recommend aspirin, 75 to 100 mg/d, indefi- nitely (Grade 1A). We suggest that the aspirin be started postoperatively (Grade 2A). 4.1.6. For patients undergoing CABG, we rec- ommend against addition of dipyridamole to aspirin therapy (Grade 1A). 4.1.8. For patients with CAD undergoing CABG who are allergic to aspirin, we recommend clopidogrel, 300 mg, as a loading dose 6 h after operation followed by 75 mg/d po indefinitely (Grade 1B). 4.1.8.1. In patients who undergo CABG following NSTE-ACS, we suggest clopidogrel, 75mg/d, for 9 to 12 months following the procedure in addition to treatment with aspirin (Grade 2B). 4.1.8.2. For patients who have received clopi- dogrel for ACS and are scheduled for CABG, we suggest discontinuing clopidogrel for 5 days prior to the scheduled surgery (Grade 2A). 4.1.10. For patients undergoing CABG who have no other indication for VKA, we recommend cli- nicians not administer VKAs (Grade 1C). 4.1.10.1. For patients undergoing CABG in whom oral anticoagulants are indicated, such as those with heart valve replacement, we suggest clinicians administer VKA in addition to aspirin (Grade 2C). 4.2.1. For all patients with CAD who undergo internal mammary artery (IMA) bypass graft- ing, we recommend aspirin, 75 to 162 mg/d, indefinitely (Grade 1A). 4.2.2. For all patients undergoing IMA bypass grafting who have no other indication for VKAs, we recommend against using VKAs (Grade 1C). 5.0. 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%), we recommend 75–100 mg/d of aspirin over either no antithrombotic ther- apy or VKA (Grade 2A). 5.1. For patients at particularly high risk of events in whom INR can be monitored without difficulty, we suggest low-dose VKA with a tar- get INR of approximately 1.5 over aspirin ther- apy (Grade 2A). 5.3. For all patients we recommend against the routine addition of clopidogrel to aspirin ther- apy in primary prevention (Grade 1A). For pa- tients with an aspirin allergy who are at moder- ate to high risk for a cardiovascular event, we recommend monotherapy with clopidogrel (Grade 1B). 5.4. For women < 65 years of age who are at risk for an ischemic stroke, and in whom the concomitant risk of major bleeding is low, we suggest aspirin at a dose of 75–100 mg/d over no aspirin therapy (Grade 2A). 5.4.1. For women > 65 years of age at risk for ischemic stroke or MI, and in whom the con- comitant risk of major bleeding is low, we suggest asprin at a dose of 75–100 mg/d over no aspirin therapy (Grade 2B). Values and preferences: The recommendation of aspirin over VKA places a relatively low value on a small absolute reduction in coronary events and deaths and a relatively high value on avoiding the inconvenience, cost, and minor bleeding risk associated with oral VKA. The low target INR value required in primary prevention typically mandates less frequent monitoring; on average every 2 to 3 months and is associated with lower risk of bleeding. Patients, particularly those in the highest risk groups for whom systems permitting meticulous monitoring of anticoagulant therapy are available, who place a relatively high value on small absolute risk reductions in coronary events and are not influ- enced by an element of inconvenience and potential bleeding risk associated with VKA are likely to derive the greatest overall benefit from administration of VKA rather than aspirin. A ntithrombotic therapy is a mainstay in themanagement of patients with either acute or chronic coronary artery disease (CAD). The fol- lowing chapter is devoted to the subject of chronic CAD and antithrombotic strategies designed for primary and secondary prevention of cardiovascu- lar events. The ACC/AHA Guidelines for the Management of Patients With Unstable Angina and Non-ST Seg- ment Elevation Myocardial Infarction reflect a management-oriented nomenclature.1 Patients with acute myocardial ischemia identified as having an acute coronary syndrome (ACS) are further differ- entiated into ACS with or without ST-segment ele- 778S Antithrombotic and Thrombolytic Therapy 8th Ed: ACCP Guidelines © 2008 American College of Chest Physicians by guest on July 23, 2011chestjournal.chestpubs.orgDownloaded from vation (STE). The early treatment decisions are influenced by this distinction. This initial distinction has little influence on secondary prevention treat- ment strategy; therefore, the recommendations for long-term antithrombotic therapy following ACS are considered together. This chapter considers the treatment of the fol- lowing patient groups: (1) post-STE ACS; (2) post- non-STE (NSTE) ACS; (3) after percutaneous cor- onary intervention (PCI); (4) stable CAD; (5) congestive heart failure (CHF); (6) after coronary artery bypass grafting (CABG): and (7) coronary heart disease (CHD) risk factors. Table 1 describes both the question definition and eligibility criteria for studies considered in each section of the anti- thrombotic therapy recommendations that follow. 1.0 Post-STE and NSTS ACS Treatment The following discussion and recommendations for post-STE and NSTE ACS management desig- nate hospital discharge as an initiating point for the transition from short-term care to long-term care and the secondary prevention of cardiovascular events. 1.1 Antiplatelet Therapies 1.1.1 Short-term Antiplatelet Therapy Trials ISIS-22 was a randomized, placebo-controlled, blinded trial of short-term therapy with IV streptoki- nase (SK), oral aspirin [160 mg/d for 1 month], both or neither among 17,187 patients with suspected myocardial infarction (MI). In addition to a 23% relative risk reduction (RRR) in 5-week vascular Table 1—Question Definition and Eligibility Criteria for Antithrombotic Agents in CAD (Section: Introduction) Section Population Intervention(s) or Exposure Outcome Methodology 1.1.1 STE and NSTE ACS Aspirin Mortality RCTs MI Stroke Bleeding 1.1.2 NSTE ACS Thienopyridines Composite: death, MI, stroke RCTs Ischemia Bleeding 1.2.1 NSTE ACS UFH Composite: death, MI RCTs Ischemia Bleeding 1.2.2 NSTE ACS LMWHs Composite: death, MI RCTs Ischemia Bleeding 1.2.3 NSTE ACS Antithrombin therapy, indirect, selective factor Xa inhibitors Composite: death, MI Ischemia Bleeding RCTs and observational studies 2.1 After MI and after ACS (secondary prevention) Oral VKA Composite: death, MI, stroke Bleeding RCTs 2.2 After MI and after ACS (secondary prevention) Aspirin combined with oral VKA Composite: death, MI, stroke Angiographic outcomes Bleeding RCTs 2.3 After MI and after ACS (secondary prevention) HMG-CoA reductase inhibitors Composite: death, MI, stroke Angiographic outcomes Bleeding RCTs 2.54 PCI Oral antiplatelet therapies (aspirin and thienopyridines) Mortality RCTs After MI and after ACS (secondary prevention) MI Stent thrombosis Observational studies 3.1 CHF Oral antiplatelet therapies with and without ACEIs and oral VKAs Composite: death, MI, stroke Bleeding RCTs and observational studies 4.1 CABG Oral antiplatelet therapies and oral VKA Graft patency RCTs and observational studies 5.1 Primary prevention Oral antiplatelet and anticoagulant therapy Mortality MI Stroke Bleeding RCTs www.chestjournal.org CHEST / 133 / 6 / JUNE, 2008 SUPPLEMENT 779S © 2008 American College of Chest Physicians by guest on July 23, 2011chestjournal.chestpubs.orgDownloaded from mortality among patients receiving SK, there was a 21% reduction among those receiving aspirin and a 40% reduction among those receiving a combination of SK and aspirin, which are all highly significant reductions. The early reduction in mortality with aspirin persisted when the patients were observed for a mean of 15 months. Aspirin reduced the risk of nonfatal reinfarction by 49% and nonfatal stroke by 46%. The increased rate of early nonfatal reinfarc- tion noted when SK therapy was used alone is consistent with marked platelet activation after fi- brinolytic therapy and was completely resolved when aspirin was added (3.8% vs 1.3%; p� 0.001). Aspirin added to the benefit of SK therapy in all groups examined. In particular, among patients� 70 years of age, the combination markedly reduced mortality from 23.8 to 15.8% (p� 0.001) without increasing hemorrhage or stroke. Because of the overall poor prognosis among older individuals with acute MI, the absolute number of lives saved with aspirin and thrombolytic therapy increases with age (ie, 2.5 per 100 treated patients � 60 years of age and 7 to 8 per 100 treated patients � 60 years of age). ISIS-2 showed that short-term aspirin therapy for MI decreases mortality and reinfa