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1 american Journal of GastroenterologyISSN 0002-9270C 2008 by Am. Coll. of Gastroenterologydoi: by Blackwell PublishingCLINICAL REVIEWSThis article is copublished in the November 2008 issue of theAmerican Journal ofGastroenterologyand the October 28, 2008, issue 2008 Expert Consensus Documenton Reducing the Gastrointestinal Risks of AntiplateletTherapy and NSAID UseWriting Committee Members: Deepak L. Bhatt, , , ,Co-Chair,James Scheiman, , ,Co-Chair,1 Neena S. Abraham, , , M. Antman, , , ,2 Francis Chan, , ,1 Curt D. Furberg, , ,2 David A. Johnson, , ,1 Kenneth W. Mahaffey, , , Eamonn M. Quigley, , ,1 ACCF Task Force Members: Robert A. Harrington, , , Eric R. Bates, , ,Charles R.

2 Bridges, , , , Mark J. Eisenberg, , , , Victor A. Ferrari, , , Mark A. Hlatky, , , Sanjay Kaul, , , Jonathan R. Lindner, , J. Moliterno, , , Debabrata Mukherjee, , , Richard S. Schofield, , ,3 Robert S. Rosenson, , , James H. Stein, , , Howard H. Weitz, , , and Deborah J. Wesley, , College of Gastroenterology Representative;2 american Heart Association Representative; and3 Former Task Force member during this writing effort(Am J Gastroenterol 2008;103:2890 2907)TABLE OF of Use NSAIDs/Aspirin (ASA)..2891 Mechanisms of GI Injury Effects of Effects of Combined ASA and Effects of Effects of Combined Clopidogrel and Anticoagu-lant and Prevention of ASA- and NSAID-Related Gastroduodenal ofH.

3 Diagnosis ofH. Tests for ActiveH. Treatment ofH. Report of the american College of Cardiology Foundation Task Force on ClinicalExpert Consensus of Antiplatelet Therapy Because in Patients on Mono- or Dual document has been developed by the american Collegeof Cardiology Foundation (ACCF) Task Force on ClinicalExpert Consensus Documents, the american College of Gas-troenterology (ACG), and the american Heart Association(AHA). Expert consensus documents (ECDs) are intendedto inform practitioners, payers, and other interested partiesof the opinion of the ACCF and document cosponsors con-cerning evolving areas of CLINICAL practice and/or technolo-gies that are widely available or new to the practice commu-nity.

4 Topics chosen for coverage by ECDs are so designedbecause the evidence base, the experience with technology,and/or the CLINICAL practice are not considered sufficientlywell developed to be evaluated by the formal american Col-lege of Cardiology/ american Heart Association (ACC/AHA)2890 ACCF/ACG/AHA Expert Consensus Document: Antiplatelets, NSAIDs, and GI Risk2891practice guidelines process. Often the topic is the subject ofongoing investigation. Thus, the reader should view ECDsas the best attempt of the ACCF and other cosponsors toinform and guide CLINICAL practice in areas where rigorousevidence may not be available or the evidence to date is notwidely accepted. When feasible, ECDs include indicationsor contraindications.

5 Topics covered by ECDs may be ad-dressed subsequently by the ACC/AHA Practice GuidelinesCommittee as new evidence evolves and is Task Force on ECDs makes every effort to avoid anyactual or potential conflicts of interest that might arise asa result of an outside relationship or personal interest of amember of the writing panel. Specifically, all members of thewriting panel are asked to provide disclosure statements of allsuch relationships that might be perceived as real or potentialconflicts of interest to inform the writing effort. These state-ments are reviewed by the parent task force, reported orallyto all members of the writing panel at thefirst meeting, andupdated as changes occur.

6 The relationships with industry in-formation for writing committee members and peer reviewersare listed in Appendixes 1 and 2, A. Harrington, , , ACCF Task Force onClinical Expert Consensus DocumentsIntroductionThe use of antiplatelet therapies continues to increase as aresult of accumulation of evidence of benefits in both pri-mary and secondary treatment strategies for cardiovasculardisease (1, 2). These antiplatelet agents, however, have rec-ognizable risks in particular, gastrointestinal (GI) compli-cations such as ulceration and related bleeding. These risksmay be further compounded by the ancillary use of other ad-junctive medications, such as nonsteroidal anti-inflammatorydrugs (NSAIDs), corticosteroids, and anticoagulants.

7 Giventhe high prevalence of antiplatelet therapy in CLINICAL prac-tice, coupled with a greater emphasis on their extended use,especially after implantation of a drug-eluting stent (3, 4), itis imperative that physicians know the potential benefits andthe associated risks of antiplatelet therapy for primary or sec-ondary prevention of cardiac ischemic events when combinedwith NSAID agents. Only with this understanding can physi-cians appropriately and fully evaluate the risk profile for eachpatient and either change medications or initiate prophylactictherapy in an attempt to reduce GI complications. This docu-ment provides consensus recommendations from the ACCF,the AHA, and the ACG on the combined use of antiplateletsand NSAID NSAIDs, both selective and nonselective, increasethe risk of cardiovascular and cerebrovascular events.

8 Thisissue was addressed in a scientific statement from the AHA(5). In terms of cardiovascular, GI, renal, and hypertension-inducing risks, there are important differences among theNSAIDs (especially the cyclo-oxygenase-2 [COX-2] in-hibitors), which should also be understood and consideredin managing patients in need of these agents (6). The AHAstatement introduces a stepped-care approach for selection ofdrugs to manage musculoskeletal discomfort in patients withknown cardiovascular disease or risk factors for ischemicheart disease, based on the risk/benefit balance from a car-diovascular perspective. A further discussion of the cardio-vascular and cerebrovascular risks of NSAIDs is beyond thescope of this report but may be found in several reviews(5, 7).

9 Prevalence of Use NSAIDs/Aspirin (ASA)The use of NSAIDs, including ASA, is common in the treat-ment of pain, inflammation, and fever. Additionally, low-doseASA is used routinely in primary and secondary prophylaxisof cardiovascular and cerebrovascular events. These agents,both through prescription and over-the-counter (OTC) use,are the most widely used class of medications in the UnitedStates (8). Not surprisingly, NSAID use increases among theelderly. In a survey of people 65 yr of age and older, 70%used NSAIDs at least once weekly, and 34% used them atleast daily. The prevalence of at least weekly ASA usage was60% (9). More than 111 million NSAID prescriptions werewritten in 2004 (10).Recognizably, much of this usage comes from noncar-diac indications, such as arthritis and related musculoskeletalcomplaints, in particular.

10 In 1990, the estimated prevalenceof self-reported arthritis in the United States was mil-lion cases, or 15% of the population. By 2020, it is projectedthat million will be affected a 57% increase from 1990(11). As the incidence of arthritis complaints increases, theuse of prescription and OTC NSAIDs is also expected of GI Injury NSAIDsA complete discussion of the pathogenesis of ASA- andNSAID-associated injury is beyond the scope of this article;however, ASA, like all NSAIDs, injures the gut by caus-ing topical injury to the mucosa and systemic effects in-duced by prostaglandin depletion. Tissue prostaglandins areproduced via 2 pathways: a COX-1 and a COX-2 COX-1 pathway is the predominant constitutive path-way; prostaglandins derived from this enzyme mediate manyeffects, most notably facilitating gastroduodenal cytoprotec-tion, renal perfusion, and platelet activity.