吲哚布芬(美国胸科协会抗血小板药物指南)

DOI 10.1378/chest.08-0672

2008;133;199S-233S Chest

Carlo Patrono, Colin Baigent, Jack Hirsh and Gerald Roth

*

Antiplatelet Drugs

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Antiplatelet Drugs*

American College of Chest Physicians

Evidence-Based Clinical Practice Guidelines

(8th Edition)

Carlo Patrono,MD;Colin Baigent,MD;Jack Hirsh,MD,FCCP;

and Gerald Roth,MD

This article about currently available antiplatelet drugs is part of the Antithrombotic and Thrombo-lytic Therapy:American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition).It describes the mechanism of action,pharmacokinetics,and pharmacodynamics of aspirin,reversible cyclooxygenase inhibitors,thienopyridines,and integrin␣IIb␤3receptor antago-nists.The relationships among dose,efficacy,and safety are thoroughly discussed,with a mechanistic overview of randomized clinical trials.The article does not provide specific management recommen-dations;however,it does highlight important practical aspects related to antiplatelet therapy, including the optimal dose of aspirin,the variable balance of benefits and hazards in different clinical settings,and the issue of interindividual variability in response to antiplatelet drugs.

(CHEST2008;133:199S–233S)

Key words:abciximab;antiplatelet drugs;aspirin;clopidogrel;dipyridamole;eptifibatide;platelet pharmacology;resistance; ticlopidine;tirofiban

Abbreviations:ACEϭangiotensin-converting enzyme;ADPϭadenosine diphosphate;AMPϭadenosine monophos-phate;ATTϭAntithrombotic Trialists;CAPRIEϭClopidogrel vs Aspirin in Patients at Risk of Ischemic Events; CHDϭcoronary heart disease;CIϭconfidence interval;COMMITϭClopidogrel and Metoprolol Myocardial Infarction Trial;COXϭcyclooxygenase;CUREϭClopidogrel in Unstable Angina to Prevent Recurrent Events;EPICϭEvaluation of 7E3for the Prevention of Ischemic Complications;ESPSϭEuropean Stroke Prevention Study;ESPRITϭEuropean Stroke Prevention Reversible Ischemia Trial;FDAϭFood and Drug Administration;GPϭglycoprotein;INRϭinternational normalized ratio;MIϭmyocardial infarction;NSAIDϭnonsteroidal antiinflammatory drug;ORϭodds ratio; PCIϭpercutaneous coronary intervention;PEϭpulmonary embolism;PGϭprostaglandin;PTCAϭpercutaneous trans-luminal coronary angioplasty;RRϭrate ratio;TIAϭtransient ischemic attack;TXϭthromboxane;TTPϭthrombotic thrombocytopenic purpura

P latelets are vital components of normal hemosta-sis and key participants in atherothrombosis by virtue of their capacity to adhere to injured blood vessels and to accumulate at sites of injury.1Al-though platelet adhesion and activation can be viewed as a physiologic repair response to the sud-den fissuring or rupture of an atherosclerotic plaque, uncontrolled progression of such a process through a series of self-sustaining amplification loops can lead to intraluminal thrombus formation,vascular occlu-sion,and transient ischemia or infarction.Currently available antiplatelet drugs interfere with some steps in the activation process,including adhesion,release, and/or aggregation,1and have a measurable impact on the risk of arterial thrombosis that cannot be dissociated from an increased risk of bleeding.2

In discussing antiplatelet drugs,it is important to appreciate that approximately1011platelets are pro-duced each day under physiologic circumstances,a level of production that can increase up to10-fold at

*From the Catholic University School of Medicine(Dr.Patrono), Rome,Italy;Clinical Trial Service Unit(Dr.Baigent),University of Oxford,Oxford,UK;Hamilton Civic Hospitals(Dr.Hirsh), Henderson Research Centre,Hamilton,ON,Canada;and Seattle VA Medical Center(Dr.Roth),Seattle,WA.

Dr.Patrono was supported in part by a grant from the European Commission FP6(LSHM-CT-2004-005033).

Manauscript accepted December20,2007.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians(www.chestjournal. org/misc/reprints.shtml).

Correspondence to:Carlo Patrono,MD,Catholic University School of Medicine,Largo F.Vito1,00168Rome,Italy;e-mail: carlo.patrono@rm.unicatt.it

DOI:10.1378/chest.08-0672Supplement

ANTITHROMBOTIC AND THROMBOLYTIC THERAPY8TH ED:ACCP GUIDELINES CHEST/133/6/JUNE,2008SUPPLEMENT199S