The Primary and Secondary Prevention of Coronary Artery Disease

American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition)


      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).

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        • Braunwald E
        • Antman EM
        • Beasley JW
        • et al.
        ACC/AHA Guidelines for the Management of Patients With Unstable Angina and Non-ST-Segment Elevation Myocardial Infarction: executive Summary and Recommendations; a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on the Management of Patients With Unstable Angina).
        Circulation. 2000; 102: 1193-1209
        • ISIS-2 (Second International Study of Infarct Survival) Collaborative Group
        Randomised trial of intravenous streptokinase, oral aspirin, both, or neither among 17,187 cases of suspected acute myocardial infarction: ISIS-2.
        Lancet. 1988; 2: 349-360
        • Sabatine MS
        • Cannon CP
        • Gibson CM
        • et al.
        Addition of clopidogrel to aspirin and fibrinolytic therapy for myocardial infarction with ST-segment elevation.
        N Engl J Med. 2005; 352: 1179-1189
        • Chen ZM
        • Jiang LX
        • Chen YP
        • et al.
        Addition of clopidogrel to aspirin in 45,852 patients with acute myocardial infarction: randomized placebo-controlled trial.
        Lancet. 2005; 366: 1607-1621
        • Antithrombotic Therapy Trialists Collaboration
        Collaborative meta-analysis of randomized trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients.
        BMJ. 2002; 324: 71-86
        • Campbell CL
        • Smyth S
        • Montalescot G
        • et al.
        Aspirin dose for the prevention of cardiovascular disease: a systematic review.
        JAMA. 2007; 297: 2018-2024
        • Bhatt DL
        • Fox KAA
        • Hacke W
        • et al.
        Clopidogrel and aspirin versus aspirin alone for the prevention of atherothrombotic events.
        N Engl J Med. 2006; 354: 1706-1717
        • Bhatt DL
        • Flather MD
        • Hacke W
        • et al.
        Patients with prior myocardial infarction, stroke, or symptomatic peripheral arterial disease in the CHARISMA trial.
        J Am Coll Cardiol. 2007; 49: 1982-1988
        • McQuaid KR
        • Laine L
        Systematic review and meta-analysis of adverse events of low-dose aspirin and clopidogrel in randomized controlled trials.
        Am J Med. 2006; 119: 624-638
        • CAPRIE Steering Committee
        A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE).
        Lancet. 1996; 348: 1329-1339
        • Yusuf S
        • Zhao F
        • Mehta S
        • et al.
        Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation.
        N Engl J Med. 2001; 345: 494-502
        • Yusuf S
        • Mehta S
        • Zhao F
        • et al.
        Early and late effects of clopidogrel in patients with acute coronary syndromes.
        Circulation. 2003; 107: 966-972
        • Diener H
        • Bogousslavsky J
        • Brass L
        Aspirin and clopidogrel compared with clopidogrel alone after recent ischemic storke or transient ischaemic attack in high-risk patients (MATCH) randomised, double-blind, placebo-controlled trial.
        Lancet. 2004; 364: 331-337
        • Gaspoz J-M
        • Coxson PG
        • Goldman PA
        • et al.
        Cost effectiveness of aspirin, clopidogrel, or both for secondary prevention of coronary heart disease.
        N Engl J Med. 2002; 346: 1800-1806
        • Schleinitz MD
        • Heidenreich PA
        A cost-effectiveness analysis of combination antiplatelet therapy for high-risk acute coronary syndromes: clopidogrel plus aspirin versus aspirin alone.
        Ann Intern Med. 2005; 142: 251-259
        • Weintraub WS
        • Mahoney EM
        • Lamy A
        • et al.
        Long-term cost-effectiveness of clopidogrel given for up to one year in patients with acute coronary syndromes without ST-segment elevation.
        J Am Coll Cardiol. 2005; 45: 838-845
        • Anand S
        • Yusuf S
        Oral anticoagulant therapy in patients with coronary artery disease: a meta-analysis.
        JAMA. 1999; 282: 2058-2067
        • Report of the Sixty Plus Reinfarction Study Research Group
        A double-blind trial to assess long-term oral anticoagulant therapy in elderly patients after myocardial infarction.
        Lancet. 1980; 2: 989-994
        • Smith P
        • Arnesen H
        • Holme I
        The effect of warfarin on mortality and reinfarction after myocardial infarction.
        N Engl J Med. 1990; 323: 147-152
        • Anticoagulants in the Secondary Prevention of Events in Coronary Thrombosis (ASPECT) Research Group
        Effect of long-term oral anticoagulant treatment on mortality and cardiovascular morbidity after myocardial infarction.
        Lancet. 1994; 343: 499-503
        • Neri Serneri GG
        • Gensini GF
        • Carnovali M
        • et al.
        Effectiveness of low-dose heparin in prevention of myocardial reinfarction.
        Lancet. 1987; 1: 937-942
        • Breddin K
        • Loew D
        • Lechner K
        • et al.
        The German-Austrian aspirin trial: a comparison of acetylsalicylic acid, placebo and phenprocoumon in secondary prevention of myocardial infarction; on behalf of the German-Austrian Study Group.
        Circulation. 1980; 62: V63-V72
        • A controlled comparison of aspirin and oral anticoagulants in prevention of death after myocardial infarction
        N Engl J Med. 1982; 307: 701-708
        • Julian DG
        • Chamberlain DA
        • Pocock SJ
        A comparison of aspirin and anticoagulation following thrombolysis for myocardial infarction (the AFTER study): a multicentre unblinded randomised clinical trial.
        BMJ. 1996; 313: 1429-1431
        • Coumadin Aspirin Reinfarction Study (CARS) Investigators
        Randomised double-blind trial of fixed low-dose warfarin with aspirin after myocardial infarction.
        Lancet. 1997; 350: 389-396
        • Thrombosis prevention trial: randomised trial of low-intensity oral anticoagulation with warfarin and low-dose aspirin in the primary prevention of ischaemic heart disease in men at increased risk.
        Lancet. 1998; 351: 233-241
        • Fiore LD
        • Ezekowitz MD
        • Brophy MT
        • et al.
        Department of Veterans Affairs Cooperative Studies Program Clinical Trial comparing combined warfarin and aspirin with aspirin alone in survivors of acute myocardial infarction: primary results of the CHAMP study.
        Circulation. 2002; 105: 557-563
        • Anand SS
        • Yusuf S
        • Pogue J
        • et al.
        Long-term oral anticoagulant therapy in patients with unstable angina or suspected non-Q-wave myocardial infarction: organization to assess strategies for ischemic syndromes (OASIS) pilot study results.
        Circulation. 1998; 98: 1064-1070
        • Brouwer MA
        • van den Bergh PJPC
        • Aengevaeren WRM
        • et al.
        Aspirin plus coumarin versus aspirin alone in the prevention of reocclusion after fibrinolysis for acute myocardial infarction: results of the Antithrombotics in the Prevention of Reocclusion in Coronary Thrombolysis (APRICOT)-2 Trial.
        Circulation. 2002; 106: 659-665
        • van Es RF
        • Jonker JJ
        • Verheugt FW
        • et al.
        Aspirin and coumadin after acute coronary syndromes (the ASPECT-2 study): a randomised controlled trial.
        Lancet. 2002; 360: 109-113
        • Hurlen M
        • Abdelnoor M
        • Smith P
        • et al.
        Warfarin, aspirin, or both after myocardial infarction.
        N Engl J Med. 2002; 347: 969-974
        • Becker RC
        Antithrombotic therapy after myocardial infarction.
        N Engl J Med. 2002; 347: 1019-1022
        • Rothberg MB
        • Celestin C
        • Fiore LD
        • et al.
        Warfarin plus aspirin after myocardial infarction or the acute coronary syndrome: meta-analysis with estimates of risk and benefit.
        Ann Intern Med. 2005; 143: 241-250
        • Fanikos J
        • Grasso-Correnti N
        • Shah R
        • et al.
        Major bleeding complications in a specialized anticoagulation service.
        Am J Cardiol. 2005; 96: 595-598
        • Andreotti F
        • Becker RC
        Atherothrombotic disorders: new insights from hematology.
        Circulation. 2005; 111: 1855-1863
        • Menzin J
        • Boulanger L
        • Hauch O
        • et al.
        Quality of anticoagulation control and costs of monitoring warfarin therapy among patients with atrial fibrillation in clinic settings: a multi-site managed-care study.
        Ann Pharmacother. 2005; 39: 446-451
        • Sullivan PW
        • Arant TW
        • Ellis SL
        • et al.
        The cost effectiveness of anticoagulation management services for patients with atrial fibrillation and at high risk of stroke in the US.
        Pharmacoeconomics. 2006; 24: 1021-1033
        • Cheung DS
        • Heizer D
        • Wilson J
        • et al.
        Cost-savings analysis of using a portable coagulometer for monitoring homebound elderly patients taking warfarin.
        Am J Geriatr Cardiol. 2003; 12: 283-287
        • You JH
        • Chan FW
        • Wong RS
        • et al.
        The potential clinical and economic outcomes of pharmacogenetics-oriented management of warfarin therapy: a decision analysis.
        Thromb Haemost. 2004; 92: 590-597
        • Mehta S
        • Yusuf S
        • Peters R
        • et al.
        Effects of pretreatment with clopidogrel and aspirin followed by long-term therapy in patients undergoing percutaneous coronary intervention: the PCI-CURE study.
        Lancet. 2001; 358: 527-533
        • Peters RJ
        • Mehta SR
        • Fox KA
        • et al.
        Effects of aspirin dose when used alone or in combination with clopidogrel in patients with acute coronary syndromes: observations from the Clopidogrel in Unstable angina to prevent Recurrent Events (CURE) study.
        Circulation. 2003; 108: 1682-1687
        • Steinhubl S
        • Berger P
        • Mann J
        • et al.
        Early and sustained dual oral antiplatelet therapy following percutaneous coronary intervention: a randomized controlled trial.
        JAMA. 2002; 288: 2411-2420
        • Kastrati A
        • Mehilli J
        • Pache J
        • et al.
        Analysis of 14 trials comparing sirolimus-eluting stents with bare-metal stents.
        N Engl J Med. 2007; 356: 1030-1039
        • Stone GW
        • Moses JW
        • Ellis SG
        • et al.
        Safety and efficacy of sirolimus- and paclitaxel-eluting coronary stents.
        N Engl J Med. 2007; 356: 998-1008
        • Maisel WH
        Unanswered questions: drug-eluting stents and the risk of late thrombosis.
        N Engl J Med. 2007; 356: 981-984
        • Mauri L
        • Hsieh WH
        • Massaro JM
        • et al.
        Stent thrombosis in randomized clinical trials of drug-eluting stents.
        N Engl J Med. 2007; 356: 1020-1029
        • Pfisterer M
        • Brunner-La Rocca HP
        • Buser PT
        • et al.
        Late clinical events after clopidogrel discontinuation may limit the benefit of drug-eluting stents: an observational study of drug-eluting versus bare-metal stents.
        J Am Coll Cardiol. 2006; 48: 2584-2591
        • Lagerqvist B
        • James SK
        • Stenestrand U
        • et al.
        Long-term outcomes with drug-eluting stents versus bare-metal stents in Sweden.
        N Engl J Med. 2007; 356: 1009-1019
        • Win HK
        • Caldera AE
        • Maresh K
        • et al.
        Clinical outcomes and stent thrombosis following off-label use of drug-eluting stents.
        JAMA. 2007; 297: 2001-2009
        • Tolleson TR
        • Newby LK
        • Harrington RA
        • et al.
        Frequency of stent thrombosis after acute coronary syndromes (from the SYMPHONY and 2nd SYMPHONY trials).
        Am J Cardiol. 2003; 92: 330-333
        • Iakovou I
        • Schmidt T
        • Bonizzoni E
        • et al.
        Incidence, predictors, and outcome of thrombosis after successful implantation of drug-eluting stents.
        JAMA. 2005; 293: 2126-2130
        • Finn AV
        • Nakazawa G
        • Joner M
        • et al.
        Vascular responses to drug eluting stents: importance of delayed healing.
        Arterioscler Thromb Vasc Biol. 2007; 27: 1500-1510
        • Finn AV
        • Kolodgie FD
        • Harnek J
        • et al.
        Differential response of delayed healing and persistent inflammation at sites of overlapping sirolimus- or paclitaxel-eluting stents.
        Circulation. 2005; 112: 270-278
        • Spertus JA
        • Kettelkamp R
        • Vance C
        • et al.
        Prevalence, predictors, and outcomes of premature discontinuation of thienopyridine therapy after drug-eluting stent placement: results from the PREMIER registry.
        Circulation. 2006; 113: 2803-2809
        • Eisenstein EL
        • Anstrom KJ
        • Kong DF
        • et al.
        Clopidogrel use and long-term clinical outcomes after drug-eluting stent implantation.
        JAMA. 2007; 297: 159-168
        • Bavry AA
        • Bhatt DL
        Drug-eluting stents: dual antiplatelet therapy for every survivor?.
        Circulation. 2007; 116: 696-699
        • Grines CL
        • Bonow RO
        • Casey Jr, DE
        • et al.
        Prevention of premature discontinuation of dual antiplatelet therapy in patients with coronary artery stents: a science advisory from the American Heart Association, American College of Cardiology, Society for Cardiovascular Angiography and Interventions, American College of Surgeons, and American Dental Association, with representation from the American College of Physicians.
        Circulation. 2007; 115: 813-818
        • Wang T
        • Robinson LA
        • Ou FS
        • et al.
        Discharge antithrombotic strategies among patients with acute coronary syndrome previously on warfarin anticoagulation: physician practice in the CRUSADE registry.
        Am Heart J. 2008; 155: 361-368
        • Nguyen MC
        • Lim YL
        • Walton A
        • et al.
        Combining warfarin and antiplatelet therapy after coronary stenting in the Global Registry of Acute Coronary Events: is it safe and effective to use just one antiplatelet agent?.
        Eur Heart J. 2007; 28: 1717-1722
        • Orford J
        • Fasseas P
        • Melby S
        • et al.
        Safety and efficacy of aspirin, clopidogrel, and warfarin after coronary stent placement in patients with an indication for anticoagulation.
        Am Heart J. 2004; 147: 463-467
        • Buresly K
        • Eisenberg M
        • Zhang X
        • et al.
        Bleeding complications associated with combinations of aspirin, hienopyridine derivatives, and warfarin in elderly patients following acute myocardial infarction.
        Arch Intern Med. 2005; 165: 784-789
        • Karjalainen P
        • Porela P
        • Ylitalo A
        • et al.
        Safety and efficacy of combined antiplatelet-warfarin therapy after coronary stenting.
        Eur Heart J. 2007; 28: 726-732
        • Khurram Z
        • Chou E
        • Minutello R
        • et al.
        Combination therapy with aspirin, clopidogrel and warfarin following coronary stenting is associated with a significant risk of bleeding.
        J Invasive Cardiol. 2006; 18: 162-164
        • Beinart SC
        • Kolm P
        • Veledar E
        • et al.
        Long-term cost effectiveness of early and sustained dual oral antiplatelet therapy with clopidogrel given for up to one year after percutaneous coronary intervention results: from the Clopidogrel for the Reduction of Events During Observation (CREDO) trial.
        J Am Coll Cardiol. 2005; 46: 761-769
        • Mahoney EM
        • Mehta S
        • Yuan Y
        • et al.
        Long-term cost-effectiveness of early and sustained clopidogrel therapy for up to 1 year in patients undergoing percutaneous coronary intervention after presenting with acute coronary syndromes without ST-segment elevation.
        Am Heart J. 2006; 151: 219-227
        • Ringborg A
        • Lindgren P
        • Jönsson B
        The cost-effectiveness of dual oral antiplatelet therapy following percutaneous coronary intervention: a Swedish analysis of the CREDO trial.
        Eur J Health Econ. 2005; 6: 354-356358–362
        • Lindgren P
        • Stenestrand U
        • Malmberg K
        • et al.
        The long-term cost-effectiveness of clopidogrel plus aspirin in patients undergoing percutaneous coronary intervention in Sweden.
        Clin Ther. 2005; 27: 100-110
        • Kunishima T
        • Musha H
        • Eto F
        • et al.
        A randomized trial of aspirin versus cilostazol therapy after successful coronary stent implantation.
        Clin Ther. 1997; 19: 1058-1066
        • Park S
        • Lee C
        • Kim H
        • et al.
        Effects of cilostazol on angiographic restenosis after coronary stent placement.
        Am J Cardiol. 2000; 86: 499-503
        • Park SJ
        • Shim WH
        • Ho DS
        • et al.
        A paclitaxel-eluting stent for the prevention of coronary restenosis.
        N Engl J Med. 2003; 348: 1537-1545
        • Ochiai M
        • Isshiki T
        • Takeshita S
        • et al.
        Use of cilostazol, a novel antiplatelet agent, in a post-Palmaz-Schatz stenting regimen.
        Am J Cardiol. 1997; 79: 1471-1474
        • Tsuchikane E
        • Fukuhara A
        • Kobayashi T
        • et al.
        Impact of cilostazol on restenosis after percutaneous coronary balloon angioplasty.
        Circulation. 1999; 100: 21-26
        • Tsuchikane E
        • Katoh O
        • Sumitsuji S
        • et al.
        Impact of cilostazol on intimal proliferation after directional coronary atherectomy.
        Am Heart J. 1998; 135: 495-502
        • Yamasaki M
        • Hara K
        • Ikari Y
        • et al.
        Effects of cilostazol on late lumen loss after Palmaz-Schatz stent implantation.
        Cathet Cardiovasc Diagn. 1998; 44: 387-391
        • Sekiya M
        • Funada J
        • Watanabe K
        • et al.
        Effects of probucol and cilostazol alone and in combination on frequency of poststenting restenosis.
        Am J Cardiol. 1998; 82: 144-147
        • Douglas Jr, JS
        • Holmes Jr, DR
        • Kereiakes DJ
        • et al.
        Coronary stent restenosis in patients treated with cilostazol.
        Circulation. 2005; 112: 2826-2832
        • Lembo N
        • Black A
        • Roubin G
        • et al.
        Effect of pretreatment with aspirin versus aspirin plus dipyridamole on frequency and type of acute complications of percutaneous transluminal coronary angioplasty.
        Am J Cardiol. 1990; 65: 422-426
        • Knudtson ML
        • Flintoft VF
        • Roth DL
        • et al.
        Effect of short-term prostacyclin administration on restenosis after percutaneous transluminal coronary angioplasty.
        J Am Coll Cardiol. 1990; 15: 691-697
        • Serruys PW
        • Rutsch W
        • Heyndrickx GR
        • et al.
        Prevention of restenosis after percutaneous transluminal coronary angioplasty with thromboxane A2-receptor blockade: a randomized, double-blind, placebo-controlled trial; Coronary Artery Restenosis Prevention on Repeated Thromboxane-Antagonism Study (CARPORT).
        Circulation. 1991; 84: 1568-1580
        • Finci L
        • Höfling B
        • Ludwig B
        • et al.
        Sulotroban during and after coronary angioplasty: a double-blind, placebo controlled study.
        Z Kardiol. 1989; 78: 50-54
        • Savage MP
        • Goldberg S
        • Macdonald RG
        • et al.
        Multi-Hospital Eastern Atlantic Restenosis Trial: II. A placebo-controlled trial of thromboxane blockade in the prevention of restenosis following coronary angioplasty.
        Am Heart J. 1991; 122: 1239-1244
        • Serruys PW
        • Klein W
        • Tijssen JP
        • et al.
        Evaluation of ketanserin in the prevention of restenosis after percutaneous transluminal coronary angioplasty: a multicenter randomized double-blind placebo-controlled trial.
        Circulation. 1993; 88: 1588-1601
        • Fujita M
        • Mizuno K
        • Ho M
        • et al.
        Sarpogrelate treatment reduces restenosis after coronary stenting.
        Am Heart J. 2003; 145: E16
        • Gershlick AH
        • Spriggins D
        • Davies SW
        • et al.
        Failure of epoprostenol (prostacyclin, PGI2) to inhibit platelet aggregation and to prevent restenosis after coronary angioplasty: results of a randomised placebo controlled trial.
        Br Heart J. 1994; 71: 7-15
        • Darius H
        • Nixdorff U
        • Zander J
        • et al.
        Effects of ciprostene on restenosis rate during therapeutic transluminal coronary angioplasty.
        Agents Actions Suppl. 1992; 37: 305-311
        • Fischman DL
        • Leon MB
        • Baim DS
        • et al.
        A randomized comparison of coronary-stent placement and balloon angioplasty in the treatment of coronary artery disease: Stent Restenosis Study Investigators.
        N Engl J Med. 1994; 331: 496-501
        • Serruys P
        • de Jaegere P
        • Kiemeneij F
        • et al.
        A comparison of balloon expandable stent implantation with balloon angioplasty in patients with coronary artery disease.
        N Engl J Med. 1994; 8: 489-495
        • Leon MB
        • Baim DS
        • Popma JJ
        • et al.
        A clinical trial comparing three antithrombotic-drug regimens after coronary-artery stenting: Stent Anticoagulation Restenosis Study Investigators.
        N Engl J Med. 1998; 339: 1665-1671
        • Machraoui A
        • Germing A
        • von Dryander S
        • et al.
        Comparison of the efficacy and safety of aspirin alone with coumadin plus aspirin after provisional coronary stenting: final and follow-up results of a randomized study.
        Am Heart J. 1999; 138: 663-669
        • Thornton M
        • Gruentzig A
        • Hollman J
        • et al.
        Coumadin and aspirin in prevention of recurrence after transluminal coronary angioplasty: a randomized study.
        Circulation. 1984; 69: 721-727
        • Urban P
        • Buller N
        • Fox K
        • et al.
        Lack of effect of warfarin on the restenosis rate or on clinical outcome after balloon coronary angioplasty.
        Br Heart J. 1988; 60: 485-488
        • Garachemani A
        • Fleisch M
        • Windecker S
        • et al.
        Heparin and coumadin versus acetylsalicylic acid for prevention of restenosis after coronary angioplasty.
        Catheter Cardiovasc Interv. 2002; 55: 315-320
        • tenBerg J
        • Kelder J
        • Suttorp M
        • et al.
        A randomized trial assessing the effect of coumarins started before coronary angioplasty on restenosis: results of the 6-month angiographic substudy of the Balloon Angioplasty and Anticoagulation Study (BAAS).
        Am Heart J. 2003; 145: 58-65
        • Kastrati A
        • Schuhlen H
        • Hausleiter J
        • et al.
        Restenosis after coronary stent placement and randomization to a 4-week combined antiplatelet or anticoagulant therapy: six-month angiographic follow-up of the Intracoronary Stenting and Antithrombotic Regimen (ISAR) Trial.
        Circulation. 1997; 96: 462-467
        • Fuster V
        • Gersh B
        • Giuliani E
        The natural history of idiopathic dilated cardiomyopathy.
        Am J Cardiol. 1981; 47: 525-530
        • Loh E
        • Sutton M
        • Wun C
        • et al.
        Ventricular dysfunction and the risk of stroke after myocardial infarction.
        N Engl J Med. 1997; 336: 251-257
        • Dunkman W
        • Johnson G
        Incidence of thromboembolic events in congestive heart failure: the V-HeFT VA Cooperative Studies Group.
        Circulation. 1993; 87: 94-101
        • Chung I
        • Lip GYH
        Platelets and heart failure.
        Eur Heart J. 2006; 27: 2623-2631
        • Jafri S
        • Ozawa T
        • Mammen E
        • et al.
        Platelet function, thrombin and fibrinolytic activity in patients with heart failure.
        Eur Heart J. 1993; 14: 205-212
        • Sbarouni E
        • Bradshaw A
        • Andreotti F
        Relationship between hemostatic abnormalities and neuroendocrine activity in heart failure.
        Am Heart J. 1994; 127: 607-612
        • Yamamoto K
        • Ikeda U
        • Furuhashi K
        The coagulation system is activated in idiopathic cardiomyopathy.
        Am Coll Cardiol. 1995; 25: 1634-1640
        • O'Connor CM
        • Gurbel PA
        • Serebruany VL
        Usefulness of soluble and surface-bound P-selection in detecting heightened platelet activity in patients with congestive heart failure.
        Am J Cardiol. 1999; 83: 1345-1349
        • Davis C
        • Gurbel P
        • Gattis W
        Hemostatic abnormalities in patients with congestive heart failure: diagnostic significance and clinical challenge.
        Int J Cardiol. 2000; 75: 15-21
        • Gurbel P
        • Gattis W
        • Fuzaylov S
        Evaluation of platelets in heart failure: is platelet activity related to etiology, functional class, or clinical outcomes?.
        Am Heart J. 2002; 143: 1068-1075
        • Serebruany V
        • McKenzie M
        • Meister A
        Whole blood impedance aggregometry for the assessment of platelet function in patients with congestive heart failure (EPCOT Trial).
        Eur J Heart Fail. 2002; 4: 461-467
        • Spodick D
        • Littmann D
        Idiopathic myocardial hypertrophy.
        Am J Cardiol. 1958; 1: 610-623
        • Roberts W
        • Siegel R
        • McManus B
        Idiopathic dilated cardiomyopathy: analysis of 152 necropsy patients.
        Am J Cardiol. 1987; 60: 1340-1355
        Effects of enalapril on mortality in severe congestive heart failure: results of the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS).
        N Engl J Med. 1987; 316: 1429-1435
        • Cohn J
        • Archibald D
        • Ziesche S
        • et al.
        Effect of vasodilator therapy on mortality in chronic congestive heart failure. Results of a Veterans Administration Cooperative Study.
        N Engl J Med. 1986; 314: 1547-1552
        • Cohn J
        • Johnson G
        A comparison of enalapril with hydralazine-isosorbide dinitrate in the treatment of chronic congestive heart failure.
        N Engl J Med. 1991; 325: 303-310
        • Falk R
        • Pollak A
        Tandon & Milton Packer for the PROMISE Investigator.
        J Am Coll Cardiol. 1993; 21: 218A
        • Natterson P
        • Stevenson W
        • Saxon LA
        • et al.
        Risk of arterial embolization in 224 patients awaiting cardiac transplantation.
        Am Heart J. 1995; 129: 564-570
        • Sharma N
        • McCullough P
        • Philbin E
        Left ventricular thrombus and subsequent thromboembolism in patients with severe systolic dysfunction.
        Chest. 2000; 117: 314-320
        • Uretsky B
        • Thygesen K
        • Armsgtrong PW
        • et al.
        Acute coronary findings at autopsy in heart failure patients with sudden death: results from the assessment of treatment with lisinopril and survival (ATLAS) trial.
        Circulation. 2000; 102: 611-616
        • Lip GYH
        • Gibbs CR
        Anticoagulation for heart failure in sinus rhythm: a Cochrane systematic review.
        QJM. 2002; 95: 461-468
        • Anderson G
        • Hull E
        The effect of dicumarol upon the mortality and incidence of thromboembolic complications in congestive heart failure.
        Am Heart J. 1950; 39: 697-702
        • Harvey W
        • Finch C
        Dicumarol prophylaxis of thromboembolic disease in congestive heart failure.
        N Engl J Med. 1950; 242: 208-211
        • Griffith GC
        • Stragnell R
        • Levinson DC
        A study of the beneficial effects of anticoagulant therapy in congestive heart failure.
        Ann Intern Med. 1952; 37: 867-887
        • Lip GYH
        • Gibbs CR
        Anticoagulation for heart failure in sinus rhythm: a Cochrane systematic review.
        Q J Med. 2002; 95: 451-459
        • Cleland JG
        • Findlay I
        • Jafri S
        • et al.
        The Warfarin/Aspirin Study in Heart failure (WASH): a randomized trial comparing antithrombotic strategies for patients with heart failure.
        Am Heart J. 2004; 148: 157-164
        • Jones CG
        • Cleland JG
        Meeting report–the LIDO, HOPE, MOXCON and WASH studies: Heart Outcomes Prevention Evaluation; the Warfarin/Aspirin Study of Heart Failure.
        Eur J Heart Failure. 1999; 1: 425-431
        • Al-Khadra A
        • Salem D
        • Rand WM
        • et al.
        Antiplatelet agents and survival: a cohort analysis from the Studies of Left Ventricular Dysfunction (SOLVD) trial.
        J Am Coll Cardiol. 1998; 31: 419-425
        • Cokkinos D
        • Toutouzas P
        Antithrombotic therapy in heart failure: a randomized comparison of warfarin vs. aspirin (HELAS).
        Eur J Heart Failure. 1999; 1: 419-423
        • SOLVD I
        Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure.
        N Engl J Med. 1991; 325: 293-302
        • Massie BM
        • Krol WF
        • Ammon SE
        • et al.
        The Warfarin and Antiplatelet Therapy in Heart Failure trial (WATCH): rationale, design, and baseline patient characteristics.
        J Card Fail. 2004; 10: 101-102
        • Pullicino P
        • Thompson JL
        • Barton B
        • et al.
        Warfarin versus aspirin in patients with reduced cardiac ejection fraction (WARCEF): rationale, objectives, and design.
        J Card Fail. 2006; 12: 39-46
        • Teo KK
        • Yusuf S
        • Pfeffer M
        • et al.
        Effects of long-term treatment with angiotensin-converting-enzyme inhibitors in the presence or absence of aspirin: a systematic review.
        Lancet. 2002; 360: 1037-1043
        • McAlister FA
        • Ghali WA
        • Gong Y
        • et al.
        Aspirin use and outcomes in a community-based cohort of 7352 patients discharged after first hospitalization for heart failure.
        Circulation. 2006; 113: 2572-2578
        • Lorenz RL
        • Schacky CV
        • Weber M
        • et al.
        Improved aortocoronary bypass patency by low-dose aspirin (100 mg daily): effects on platelet aggregation and thromboxane formation.
        Lancet. 1984; 1: 1261-1264
        • Hockings BE
        • Ireland MA
        • Gotch-Martin KF
        • et al.
        Placebo-controlled trial of enteric coated aspirin in coronary bypass graft patients: effect on graft patency.
        Med J Aust. 1993; 159: 376-378
        • Sanz G
        • Pajaron A
        • Alegria E
        • et al.
        Prevention of early aortocoronary bypass occlusion by low-dose aspirin and dipyridamole: grupo Espanol para el Seguimiento del Injerto Coronario (GESIC).
        Circulation. 1990; 82: 765-773
        • Goldman S
        • Copeland J
        • Moritz T
        • et al.
        Saphenous vein graft patency 1 year after coronary artery bypass surgery and effects of antiplatelet therapy: results of a Veterans Administration Cooperative Study.
        Circulation. 1989; 80: 1190-1197
        • Goldman S
        • Copeland J
        • Moritz T
        • et al.
        Improvement in early saphenous vein graft patency after coronary artery bypass surgery with antiplatelet therapy: results of a Veterans Administration Cooperative Study.
        Circulation. 1988; 77: 1324-1332
        • Goldman S
        • Copeland J
        • Moritz T
        Long-term graft patency (3 years) after coronary artery surgery: effects of aspirin; results of a VA cooperative study.
        Circulation. 1994; 89: 1138-1143
        • Gavaghan TP
        • Gebski V
        • Baron DW
        Immediate postoperative aspirin improves vein graft patency early and late after coronary artery bypass graft surgery: a placebo-controlled, randomized study.
        Circulation. 1991; 83: 1526-1533
        • McEnany MT
        • Salzman EW
        • Mundth ED
        • et al.
        The effect of antithrombotic therapy on patency rates of saphenous vein coronary artery bypass grafts.
        J Thorac Cardiovasc Surg. 1982; 83: 81-89
        • Sharma GV
        • Khuri SF
        • Josa M
        • et al.
        The effect of antiplatelet therapy on saphenous vein coronary artery bypass graft patency.
        Circulation. 1983; 68: 218-221
        • Brown BG
        • Cukingnan RA
        • DeRouen T
        • et al.
        Improved graft patency in patients treated with platelet-inhibiting therapy after coronary bypass surgery.
        Circulation. 1985; 72: 138-146
        • Mayer Jr, JE
        • Lindsay WG
        • Castaneda W
        • et al.
        Influence of aspirin and dipyridamole on patency of coronary artery bypass grafts.
        Ann Thorac Surg. 1981; 31: 204-210
        • Rajah SM
        • Salter MC
        • Donaldson DR
        • et al.
        Acetylsalicylic acid and dipyridamole improve the early patency of aorta-coronary bypass grafts: a double-blind, placebo-controlled, randomized trial.
        J Thorac Cardiovasc Surg. 1985; 90: 373-377
        • Chesebro JH
        • Fuster V
        • Elveback LR
        • et al.
        Effect of dipyridamole and aspirin on late vein-graft patency after coronary bypass operations.
        N Engl J Med. 1984; 310: 209-214
        • Pantely GA
        • Goodnight Jr, SH
        • Rahimtoola SH
        • et al.
        Failure of antiplatelet and anticoagulant therapy to improve patency of grafts after coronary-artery bypass: a controlled, randomized study.
        N Engl J Med. 1979; 301: 962-966
        • Brooks N
        • Wright J
        • Sturridge M
        • et al.
        Randomised placebo controlled trial of aspirin and dipyridamole in the prevention of coronary vein graft occlusion.
        Br Heart J. 1985; 53: 201-207
        • Pirk J
        • Vojacek J
        • Kovac J
        • et al.
        Improved patency of the aortocoronary bypass by antithrombotic drugs.
        Ann Thorac Surg. 1986; 42: 312-314
        • Ekeström SA
        • Gunnes S
        • Brodin UB
        Effect of dipyridamole (Persantin) on blood flow and patency of aortocoronary vein bypass grafts.
        Scand J Thorac Cardiovasc Surg. 1990; 24: 191-196
        • Limet R
        • David JL
        • Magotteaux P
        • et al.
        Prevention of aorta-coronary bypass graft occlusion: beneficial effect of ticlopidine on early and late patency rates of venous coronary bypass grafts: a double-blind study.
        J Thorac Cardiovasc Surg. 1987; 94: 773-783
        • Chevigné M
        • David JL
        • Rigo P
        • et al.
        Effect of ticlopidine on saphenous vein bypass patency rates: a double-blind study.
        Ann Thorac Surg. 1984; 37: 371-378
        • Baur HR
        • VanTassel RA
        • Pierach CA
        • et al.
        Effects of sulfinpyrazone on early graft closure after myocardial revascularization.
        Am J Cardiol. 1982; 49: 420-424
        • Gohlke H
        • Gohlke-Barwolf C
        • Sturzenhofecker P
        • et al.
        Improved graft patency with anticoagulant therapy after aortocoronary bypass surgery: a prospective, randomized study.
        Circulation. 1981; 64: II22-II27
        • Martens TP
        • Argenziano M
        • Oz MC
        New technology for surgical coronary revascularization.
        Circulation. 2006; 114: 606-614
        • Gummert JF
        • Opfermann U
        • Jacobs S
        • et al.
        Anastomotic devices for coronary artery bypass grafting: technological options and potential pitfalls.
        Comput Biol Med. 2007; 37: 1384-1393
        • Parolari A
        • Alamanni F
        • Polvani G
        • et al.
        Meta-analysis of randomized trials comparing off-pump with on-pump coronary artery bypass graft patency.
        Ann Thorac Surg. 2005; 80: 2121-2125
        • Kiaii B
        • McClure RS
        • Stitt L
        • et al.
        Prospective angiographic comparison of direct, endoscopic, and telesurgical approaches to harvesting the internal thoracic artery.
        Ann Thorac Surg. 2006; 82: 624-628
        • Holzhey DM
        • Jacobs S
        • Mochalski M
        • et al.
        Seven-year follow-up after minimally invasive direct coronary artery bypass: experience with more than 1300 patients.
        Ann Thorac Surg. 2007; 83: 108-114
        • Mangano DT
        • Tudor IC
        • Dietzel C
        • et al.
        The risk associated with aprotinin in cardiac surgery.
        N Engl J Med. 2006; 354: 353-365
        • Mangano DT
        • Miao Y
        • Vuylsteke A
        • et al.
        Mortality associated with aprotinin during 5 years following coronary artery bypass graft surgery.
        JAMA. 2007; 297: 471-479
        • Antiplatelet Trialists' Collaboration
        Collaborative overview of randomised trials of antiplatelet therapy: II. Maintenance of vascular graft or arterial patency by antiplatelet therapy.
        BMJ. 1994; 308: 159-168
        • Goldman G
        • Welbourn R
        • Klausner JM
        • et al.
        Thromboxane mediates diapedesis after ischemia by activation of neutrophil adhesion receptors interacting with basally expressed intercellular adhesion molecule-1.
        Circ Res. 1991; 68: 1013-1019
        • van derMeer J
        • Hillege HL
        • Kootstra GJ
        • et al.
        Prevention of one-year vein-graft occlusion after aortocoronary-bypass surgery: a comparison of low-dose aspirin, low-dose aspirin plus dipyridamole, and oral anticoagulants; the CABADAS Research Group of the Interuniversity Cardiology Institute of The Netherlands.
        Lancet. 1993; 342: 257-264
        • Agnew TM
        • French JK
        • Neutze JM
        • et al.
        The role of dipyridamole in addition to low dose aspirin in the prevention of occlusion of coronary artery bypass grafts.
        Aust NZ J Med. 1992; 22: 665-670
        • Stein PD
        • Alpert JS
        • Dalen JE
        • et al.
        Antithrombotic therapy in patients with mechanical and biological prosthetic heart valves.
        Chest. 1998; : 602S-610S
        • Stein PD
        • Dalen JE
        • Goldman S
        • et al.
        Antithrombotic therapy in patients with saphenous vein and internal mammary artery bypass grafts.
        Chest. 1998; : 658S-665S
        • Rovelli F
        • Campolo L
        • Cataldo G
        • et al.
        Indobufen versus aspirin plus dipyridamole after coronary artery bypass surgery: effects on graft patency 1 year after surgery [abstract].
        Circulation. 1990; 82: 507
        • Rajah SM
        • Nair U
        • Rees M
        • et al.
        Effects of antiplatelet therapy with indobufen or aspirin-dipyridamole on graft patency one year after coronary artery bypass grafting.
        J Thorac Cardiovasc Surg. 1994; 107: 1146-1153
        • Rohn V
        • Pirk J
        • Mach T
        The effect of indobufen on aortocoronary bypass patency after 1 week and after 1 year.
        Cor Vasa. 1993; 35: 162-164
        • Bhatt DL
        • Chew DP
        • Hirsch AT
        • et al.
        Superiority of clopidogrel versus aspirin in patients with prior cardiac surgery.
        Circulation. 2001; 103: 363-368
        • Bennett C
        • Connors J
        • Carwile J
        • et al.
        Thrombotic thrombocytopenic purpura associated with clopidogrel.
        N Engl J Med. 2000; 342: 1773-1777
        • Moussa I
        • Oetgen M
        • Roubin G
        • et al.
        Effectiveness of clopidogrel and aspirin versus ticlopidine and aspirin in preventing stent thrombosis after coronary stent implantation.
        Circulation. 1999; 99: 2364-2366
        • Pfisterer M
        • Burkart F
        • Jockers G
        • et al.
        Trial of low-dose aspirin plus dipyridamole versus anticoagulants for prevention of aortocoronary vein graft occlusion.
        Lancet. 1989; 2: 1-7
        • Yli-Mayry S
        • Huikuri HV
        • Korhonen UR
        • et al.
        Efficacy and safety of anticoagulant therapy started pre-operatively in preventing coronary vein graft occlusion.
        Eur Heart J. 1992; 13: 1259-1264
        • Weber MA
        • Hasford J
        • Taillens C
        • et al.
        Low-dose aspirin versus anticoagulants for prevention of coronary graft occlusion.
        Am J Cardiol. 1990; 66: 1464-1468
        • Harjola PT
        • Frick MH
        • Meurala H
        • et al.
        The effect of dipyridamole and warfarin on the patency rate of coronary artery bypass grafts.
        Thorac Cardiovasc Surg. 1983; 31: 374-376
        • Goldman S
        • Copeland J
        • Moritz T
        • et al.
        Internal mammary artery and saphenous vein graft patency: effects of aspirin.
        Circulation. 1990; 82: 237-242
        • van derMeer J
        • Hillege HL
        • van Gilst WH
        • et al.
        A comparison of internal mammary artery and saphenous vein grafts after coronary artery bypass surgery: no difference in 1-year occlusion rates and clinical outcome; CABADAS Research Group of the Interuniversity Cardiology Institute of The Netherlands.
        Circulation. 1994; 90: 2367-2374
        • Ridker PM
        • Cook NR
        • Lee IM
        • et al.
        A randomized trial of low-dose aspirin in the primary prevention of cardiovascular disease in women.
        N Engl J Med. 2005; 352: 1293-1304
        • Sanmuganathan PS
        • Ghahramani P
        • Jackson PR
        • et al.
        Aspirin for primary prevention of coronary heart disease: safety and absolute benefit related to coronary risk derived from meta-analysis of randomised trials.
        Heart. 2001; 85: 265-271
        • Steering Committee of the Physicians' Health Study Research Group
        Final report on the aspirin component of the ongoing Physicians' Health Study.
        N Engl J Med. 1989; 321: 129-135
        • Peto R
        • Gray R
        • Collins R
        • et al.
        Randomised trial of prophylactic daily aspirin in British male doctors.
        BMJ (Clin Res Ed). 1988; 296: 313-316
        • Meade TW
        • Mellows S
        • Brozovic M
        • et al.
        Haemostatic function and ischaemic heart disease: principal results of the Northwick Park Heart Study.
        Lancet. 1986; 2: 533-537
        • Rudnicka AR
        • Ashby D
        • Brennan P
        • et al.
        Thrombosis prevention trial: compliance with warfarin treatment and investigation of a retained effect.
        Arch Intern Med. 2003; 163: 1454-1460
        • Hansson L
        • Zanchetti A
        • Carruthers SG
        • et al.
        Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomised trial: HOT Study Group.
        Lancet. 1998; 351: 1755-1762
        • deGaetano G
        Low-dose aspirin and vitamin E in people at cardiovascular risk: a randomised trial in general practice: collaborative Group of the Primary Prevention Project.
        Lancet. 2001; 357: 89-95
        • Hennekens CH
        • Peto R
        • Hutchison GB
        • et al.
        An overview of the British and American aspirin studies.
        N Engl J Med. 1988; 318: 923-924
        • Manson J
        • Stampfer M
        A prospective study of aspirin use and primary prevention of cardiovascular disease in women.
        JAMA. 1991; 266: 521-527
        • Berger JS
        • Roncaglioni MC
        • Avanzini F
        • et al.
        Aspirin for the primary prevention of cardiovascular events in women and men: a sex-specific meta-analysis of randomized controlled trials.
        JAMA. 2006; 295: 306-313
        • Wilson PW
        • D'Agostino RB
        • Levy D
        • et al.
        Prediction of coronary heart disease using risk factor categories.
        Circulation. 1998; 97: 1837-1847
        • Schwartz L
        • Bourassa M
        • Lesperance J
        • et al.
        Aspirin and dipyridamole in the prevention of restenosis after percutaneous transluminal coronary angioplasty.
        N Engl J Med. 1988; 318: 1714-1719
        • White C
        • Chaitman B
        • Lassar T
        • et al.
        Antiplatelet agents are effective in reducing the immediate complications of PTCA: results of the ticlopidine multicenter trial [abstract].
        Circulation. 1987; 76: 400
        • Barnathan E
        • Schwartz J
        • Taylor L
        • et al.
        Aspirin and dipyridamole in the prevention of acute coronary thrombosis complicating coronary angioplasty.
        Circulation. 1987; 76: 125-134
        • Mufson L
        • Black A
        • Roubin G
        • et al.
        A randomized trial of aspirin in PTCA: effect of high versus low dose aspirin on major complications and restenosis [abstract].
        J Am Coll Cardiol. 1988; 11: 236
        • MacIntyre IM
        • Jhund PS
        • McMurray JJ
        Aspirin inhibits the acute arterial and venous vasodilator response to captopril in patients with chronic heart failure.
        Cardiovasc Drugs Ther. 2005; 19: 261-265