The potential role of anticoagulant therapy for the secondary prevention of ischemic events post-acute coronary syndrome

References

• Hamm CW, Bassand JP, Agewall S, et al. ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: The Task Force for the Management of Acute Coronary Syndromes (ACS) in Patients Presenting without Persistent ST-segment Elevation of the European Society of Cardiology (ESC). Eur Heart J 2011;32:2999-3054
   PubMed Web of Science ®Google Scholar
• Anderson JL, Adams CD, Antman EM, et al. ACC/AHA 2007 guidelines for the management of patients with unstable angina/non-ST-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines for the Management of Patients With Unstable Angina/Non-ST-Elevation Myocardial Infarction) developed in collaboration with the American College of Emergency Physicians, the Society for Cardiovascular Angiography and Interventions, and the Society of Thoracic Surgeons endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation and the Society for Academic Emergency Medicine. J Am Coll Cardiol 2007;50:e1-157
   PubMed Web of Science ®Google Scholar
• Levine GN, Bates ER, Blankenship JC, et al. 2011 ACCF/AHA/SCAI guideline for percutaneous coronary intervention. A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Society for Cardiovascular Angiography and Interventions. J Am Coll Cardiol 2011;58:e44-122
   PubMed Web of Science ®Google Scholar
• Wright RS, Anderson JL, Adams CD, et al. 2011 ACCF/AHA focused update of the guidelines for the management of patients with unstable angina/non-ST-elevation myocardial infarction (updating the 2007 guideline): a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation 2011;123:2022-60
   PubMed Web of Science ®Google Scholar
• Vandvik PO, Lincoff AM, Gore JM, et al. Primary and secondary prevention of cardiovascular disease: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest 2012;141:e637-68S
   Web of Science ®Google Scholar
• Hochtl T, Farhan S, Wojta J, Huber K. New anticoagulant agents in acute coronary syndromes. Heart 2011;97:244-52
   PubMed Web of Science ®Google Scholar
• Jneid H, Anderson JL, Wright RS, et al. 2012 ACCF/AHA focused update of the guideline for the management of patients with unstable angina/non-ST-elevation myocardial infarction (updating the 2007 guideline and replacing the 2011 focused update): a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2012;60:645-81
   PubMed Web of Science ®Google Scholar
• O’Gara PT, Kushner FG, Ascheim DD, et al. 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation 2013;127:e362-425
   PubMed Web of Science ®Google Scholar
• Meadows TA, Bhatt DL. Clinical aspects of platelet inhibitors and thrombus formation. Circ Res 2007;100:1261-75
   PubMed Web of Science ®Google Scholar
• White HD. Oral antiplatelet therapy for atherothrombotic disease: current evidence and new directions. Am Heart J 2011;161:450-61
   PubMed Web of Science ®Google Scholar
• Yusuf S, Zhao F, Mehta SR, 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
   PubMed Web of Science ®Google Scholar
• Wiviott SD, Braunwald E, McCabe CH, et al. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2007;357:2001-15
   PubMed Web of Science ®Google Scholar
• Roe MT, Armstrong PW, Fox KA, et al. Prasugrel versus clopidogrel for acute coronary syndromes without revascularization. N Engl J Med 2012;367:1297-309
   PubMed Web of Science ®Google Scholar
• Wallentin L, Becker RC, Budaj A, et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2009;361:1045-57
   PubMed Web of Science ®Google Scholar
• Shattil SJ, Kashiwagi H, Pampori N. Integrin signaling: the platelet paradigm. Blood 1998;91:2645-57
   PubMed Web of Science ®Google Scholar
• Davi G, Patrono C. Platelet activation and atherothrombosis. N Engl J Med 2007;357:2482-94
   PubMed Web of Science ®Google Scholar
• Varga-Szabo D, Pleines I, Nieswandt B. Cell adhesion mechanisms in platelets. Arterioscler Thromb Vasc Biol 2008;28:403-12
   PubMed Web of Science ®Google Scholar
• Mackman N. Triggers, targets and treatments for thrombosis. Nature 2008;451:914-18
   PubMed Web of Science ®Google Scholar
• Turpie AGG, Esmon C. Venous and arterial thrombosis – pathogenesis and the rationale for anticoagulation. Thromb Haemost 2011;105:586-96
   PubMed Web of Science ®Google Scholar
• Kahn ML, Nakanishi-Matsui M, Shapiro MJ, et al. Protease-activated receptors 1 and 4 mediate activation of human platelets by thrombin. J Clin Invest 1999;103:879-87
   PubMed Web of Science ®Google Scholar
• Shattil SJ, Hoxie JA, Cunningham M, et al. Changes in the platelet membrane glycoprotein IIb.IIIa complex during platelet activation. J Biol Chem 1985;260:11107-14
   PubMed Web of Science ®Google Scholar
• Ruggeri ZM, Mendolicchio GL. Adhesion mechanisms in platelet function. Circ Res 2007;100:1673-85
   PubMed Web of Science ®Google Scholar
• Weisel JW, Nagaswami C, Vilaire G, et al. Examination of the platelet membrane glycoprotein IIb–IIIa complex and its interaction with fibrinogen and other ligands by electron microscopy. J Biol Chem 1992;267:16637-43
   PubMed Web of Science ®Google Scholar
• Sørensen R, Olesen JB, Charlot M, et al. Risk of bleeding related to antithrombotic treatment in cardiovascular disease. Curr Pharm Des 2012;18:5362-78
   PubMed Web of Science ®Google Scholar
• Komocsi A, Vorobcsuk A, Kehl D, et al. Use of new-generation oral anticoagulant agents in patients receiving antiplatelet therapy after an acute coronary syndrome: systematic review and meta-analysis of randomized controlled trials. Arch Intern Med 2012;172:1537-45
   PubMed Web of Science ®Google Scholar
• Oldgren J, Wallentin L, Alexander JH, et al. New oral anticoagulants in addition to single or dual antiplatelet therapy after an acute coronary syndrome: a systematic review and meta-analysis. Eur Heart J 2013;34:1670-80
   PubMed Web of Science ®Google Scholar
• GRACE risk score calculator 2.0, 2014. Available at: http://www.gracescore.org/WebSite/WebVersion.aspx [Last accessed 8 July 2014]
   Google Scholar
• CRUSADE bleeding score calculator, 2014. Available at: http://www.crusadebleedingscore.org/ [Last accessed 8 July 2014]
   Google Scholar
• Savi P, Herbert JM. Clopidogrel and ticlopidine: P2Y12 adenosine diphosphate-receptor antagonists for the prevention of atherothrombosis. Semin Thromb Hemost 2005;31:174-83
   PubMed Web of Science ®Google Scholar
• Steg PG, Mehta SR, Jukema JW, et al. RUBY-1: a randomized, double-blind, placebo-controlled trial of the safety and tolerability of the novel oral factor Xa inhibitor darexaban (YM150) following acute coronary syndrome. Eur Heart J 2011;32:2541-54
   PubMed Web of Science ®Google Scholar
• Stringer F, Scott G, Kupfer S, et al. The pharmacokinetics and pharmacodynamics of TAK-442, an oral, direct factor Xa inhibitor following multiple dosing in healthy male subjects. Br J Clin Pharmacol 2010;70:284-308. Abstract p305
   Web of Science ®Google Scholar
• Chen ZM, Jiang LX, Chen YP, et al. Addition of clopidogrel to aspirin in 45,852 patients with acute myocardial infarction: randomised placebo-controlled trial. Lancet 2005;366:1607-21
   PubMed Web of Science ®Google Scholar
• 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;352:1179-89
   PubMed Web of Science ®Google Scholar
• Verstuyft C, Simon T, Kim RB. Personalized medicine and antiplatelet therapy: ready for prime time? Eur Heart J 2009;30:1943-63
   PubMed Web of Science ®Google Scholar
• Aradi D, Komocsi A, Vorobcsuk A, et al. Prognostic significance of high on-clopidogrel platelet reactivity after percutaneous coronary intervention: systematic review and meta-analysis. Am Heart J 2010;160:543-51
   PubMed Web of Science ®Google Scholar
• Mehta SR, Tanguay JF, Eikelboom JW, et al. Double-dose versus standard-dose clopidogrel and high-dose versus low-dose aspirin in individuals undergoing percutaneous coronary intervention for acute coronary syndromes (CURRENT-OASIS 7): a randomised factorial trial. Lancet 2010;376:1233-43
   PubMed Web of Science ®Google Scholar
• Jernberg T, Payne CD, Winters KJ, et al. Prasugrel achieves greater inhibition of platelet aggregation and a lower rate of non-responders compared with clopidogrel in aspirin-treated patients with stable coronary artery disease. Eur Heart J 2006;27:1166-73
   PubMed Web of Science ®Google Scholar
• Wiviott SD, Trenk D, Frelinger AL, et al. Prasugrel compared with high loading- and maintenance-dose clopidogrel in patients with planned percutaneous coronary intervention: the Prasugrel in Comparison to Clopidogrel for Inhibition of Platelet Activation and Aggregation–Thrombolysis In Myocardial Infarction 44 trial. Circulation 2007;116:2923-32
   PubMed Web of Science ®Google Scholar
• Jakubowski JA, Winters KJ, Naganuma H, et al. Prasugrel: a novel thienopyridine antiplatelet agent. A review of preclinical and clinical studies and the mechanistic basis for its distinct antiplatelet profile. Cardiovasc Drug Rev 2007;25:357-74
   PubMed Web of Science ®Google Scholar
• Wiviott SD, Antman EM, Braunwald E. Prasugrel. Circulation 2010;122:394-403
   PubMed Web of Science ®Google Scholar
• Mega JL, Simon T, Collet JP, et al. Reduced-function CYP2C19 genotype and risk of adverse clinical outcomes among patients treated with clopidogrel predominantly for PCI: a meta-analysis. JAMA 2010;304:1821-30
   PubMed Web of Science ®Google Scholar
• AstraZeneca. Brilinta (ticagrelor) Prescribing Information. 2013. Available at: http://www1.astrazeneca-us.com/pi/brilinta.pdf [Last accessed 31 July 2013]
   Google Scholar
• Steg PG, James S, Harrington RA, et al. Ticagrelor versus clopidogrel in patients with ST-elevation acute coronary syndromes intended for reperfusion with primary percutaneous coronary intervention: a Platelet Inhibition and Patient Outcomes (PLATO) trial subgroup analysis. Circulation 2010;122:2131-41
   PubMed Web of Science ®Google Scholar
• James SK, Roe MT, Cannon CP, et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes intended for non-invasive management: substudy from prospective randomised PLATelet inhibition and patient Outcomes (PLATO) trial. Br Med J 2011;342:d3527
   PubMed Web of Science ®Google Scholar
• Becker RC, Bassand JP, Budaj A, et al. Bleeding complications with the P2Y12 receptor antagonists clopidogrel and ticagrelor in the PLATelet inhibition and patient Outcomes (PLATO) trial. Eur Heart J 2011;32:2933-44
   PubMed Web of Science ®Google Scholar
• Chew DP, Huang Z, Pieper KS, et al. Patients with non-ST-elevation acute coronary syndromes undergoing coronary artery bypass grafting in the modern era of antithrombotic therapy. Am Heart J 2008;155:239-44
   PubMed Web of Science ®Google Scholar
• Yan AT, Yan RT, Tan M, et al. In-hospital revascularization and one-year outcome of acute coronary syndrome patients stratified by the GRACE risk score. Am J Cardiol 2005;96:913-16
   PubMed Web of Science ®Google Scholar
• Fox KA, Carruthers KF, Dunbar DR, et al. Underestimated and under-recognized: the late consequences of acute coronary syndrome (GRACE UK-Belgian Study). Eur Heart J 2010;31:2755-64
   PubMed Web of Science ®Google Scholar
• Roger VL, Go AS, Lloyd-Jones DM, et al. Heart disease and stroke statistics – 2012 update: a report from the American Heart Association. Circulation 2012;125:e2-220
   PubMed Web of Science ®Google Scholar
• Suh JW, Lee SP, Park KW, et al. Multicenter randomized trial evaluating the efficacy of cilostazol on ischemic vascular complications after drug-eluting stent implantation for coronary heart disease: results of the CILON-T (influence of CILostazol-based triple antiplatelet therapy ON ischemic complication after drug-eluting stenT implantation) trial. J Am Coll Cardiol 2011;57:280-9
   PubMed Web of Science ®Google Scholar
• Angiolillo DJ, Capranzano P, Goto S, et al. A randomized study assessing the impact of cilostazol on platelet function profiles in patients with diabetes mellitus and coronary artery disease on dual antiplatelet therapy: results of the OPTIMUS-2 study. Eur Heart J 2008;29:2202-11
   PubMed Web of Science ®Google Scholar
• Chung AW, Jurasz P, Hollenberg MD, et al. Mechanisms of action of proteinase-activated receptor agonists on human platelets. Br J Pharmacol 2002;135:1123-32
   PubMed Web of Science ®Google Scholar
• Morrow DA, Braunwald E, Bonaca MP, et al. Vorapaxar in the secondary prevention of atherothrombotic events. N Engl J Med 2012;366:1404-13
   PubMed Web of Science ®Google Scholar
• Tricoci P, Huang Z, Held C, et al. Thrombin-receptor antagonist vorapaxar in acute coronary syndromes. N Engl J Med 2012;366:20-33
   PubMed Web of Science ®Google Scholar
• Leonardi S, Tricoci P, White HD, et al. Effect of vorapaxar on myocardial infarction in the thrombin receptor antagonist for clinical event reduction in acute coronary syndrome (TRA·CER) trial. Eur Heart J 2013;34:1723-31
   PubMed Web of Science ®Google Scholar
• Scirica BM, Bonaca MP, Braunwald E, et al. Vorapaxar for secondary prevention of thrombotic events for patients with previous myocardial infarction: a prespecified subgroup analysis of the TRA2°P-TIMI 50 trial. Lancet 2012;380:1317-24
   PubMed Web of Science ®Google Scholar
• Bonaca MP, Scirica BM, Creager MA, et al. Vorapaxar in patients with peripheral artery disease: results from TRA2°P-TIMI 50. Circulation 2013;127:1522-6
   PubMed Web of Science ®Google Scholar
• McKee S. Merck & Co gets FDA panel backing for vorapaxar. 2014. Available at: http://www.pharmatimes.com/andy_keywords_test/14-01-16/Merck_Co_gets_FDA_panel_backing_for_vorapaxar.aspx [Last accessed 27 January 2014]
   Google Scholar
• FDA approves Zontivity to reduce the risk of heart attacks and stroke in high-risk patients. FDA news release. 2014. Available at: http://www.fda.gov/newsevents/newsroom/pressannouncements/ucm396585.htm [Last accessed 8 July 2014]
   Google Scholar
• Wiviott SD, Flather MD, O’Donoghue ML, et al. Randomized trial of atopaxar in the treatment of patients with coronary artery disease: the lessons from antagonizing the cellular effect of Thrombin–Coronary Artery Disease Trial. Circulation 2011;123:1854-63
   PubMed Web of Science ®Google Scholar
• Van de Werf F. Inhibitors of the platelet thrombin receptor: will they live up to their promises? Circulation 2011;123:1833-5
   PubMed Web of Science ®Google Scholar
• O’Donoghue ML, Bhatt DL, Wiviott SD, et al. Safety and tolerability of atopaxar in the treatment of patients with acute coronary syndromes: the lessons from antagonizing the cellular effects of thrombin-acute coronary syndromes trial. Circulation 2011;123:1843-53
   PubMed Web of Science ®Google Scholar
• Badimon JJ, Zaman A, Helft G, et al. Acute coronary syndromes: pathophysiology and preventive priorities. Thromb Haemost 1999;82:997-1004
   PubMed Web of Science ®Google Scholar
• Chou J, Mackman N, Merrill-Skoloff G, et al. Hematopoietic cell-derived microparticle tissue factor contributes to fibrin formation during thrombus propagation. Blood 2004;104:3190-7
   PubMed Web of Science ®Google Scholar
• Owens AP III, Mackman N. Tissue factor and thrombosis: The clot starts here. Thromb Haemost 2010;104:432-9
   PubMed Web of Science ®Google Scholar
• Wilcox JN, Smith KM, Schwartz SM, et al. Localization of tissue factor in the normal vessel wall and in the atherosclerotic plaque. Proc Natl Acad Sci USA 1989;86:2839-43
   PubMed Web of Science ®Google Scholar
• Borissoff JI, Spronk HM, Heeneman S, et al. Is thrombin a key player in the ‘coagulation-atherogenesis’ maze? Cardiovasc Res 2009;82:392-403
   PubMed Web of Science ®Google Scholar
• Fuster V, Moreno PR, Fayad ZA, et al. Atherothrombosis and high-risk plaque: part I: evolving concepts. J Am Coll Cardiol 2005;46:937-54
   PubMed Web of Science ®Google Scholar
• Silvain J, Collet JP, Nagaswami C, et al. Composition of coronary thrombus in acute myocardial infarction. J Am Coll Cardiol 2011;57:1359-67
   PubMed Web of Science ®Google Scholar
• Mega JL, Morrow DA, de Lemos JA, et al. Thrombus precursor protein and clinical outcomes in patients with acute coronary syndromes. J Am Coll Cardiol 2008;51:2422-9
   PubMed Web of Science ®Google Scholar
• Skeppholm M, Kallner A, Malmqvist K, et al. Is fibrin formation and thrombin generation increased during and after an acute coronary syndrome? Thromb Res 2011;128:483-9
   PubMed Web of Science ®Google Scholar
• Undas A, Szuldrzynski K, Stepien E, et al. Reduced clot permeability and susceptibility to lysis in patients with acute coronary syndrome: effects of inflammation and oxidative stress. Atherosclerosis 2008;196:551-7
   PubMed Web of Science ®Google Scholar
• Douketis JD, Eikelboom JW, Quinlan DJ, et al. Short-duration prophylaxis against venous thromboembolism after total hip or knee replacement: a meta-analysis of prospective studies investigating symptomatic outcomes. Arch Intern Med 2002;162:1465-71
   PubMed Web of Science ®Google Scholar
• Oldgren J, Linder R, Grip L, et al. Coagulation activity and clinical outcome in unstable coronary artery disease. Arterioscler Thromb Vasc Biol 2001;21:1059-64
   PubMed Web of Science ®Google Scholar
• Li YH, Teng JK, Tsai WC, et al. Prognostic significance of elevated hemostatic markers in patients with acute myocardial infarction. J Am Coll Cardiol 1999;33:1543-8
   PubMed Web of Science ®Google Scholar
• Ardissino D, Merlini PA, Bauer KA, et al. Coagulation activation and long-term outcome in acute coronary syndromes. Blood 2003;102:2731-5
   PubMed Web of Science ®Google Scholar
• Merlini PA, Bauer KA, Oltrona L, et al. Persistent activation of coagulation mechanism in unstable angina and myocardial infarction. Circulation 1994;90:61-8
   PubMed Web of Science ®Google Scholar
• 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;360:109-13
   PubMed Web of Science ®Google Scholar
• Herlitz J, Holm J, Peterson M, et al. Effect of fixed low-dose warfarin added to aspirin in the long term after acute myocardial infarction; the LoWASA Study. Eur Heart J 2004;25:232-9
   PubMed Web of Science ®Google Scholar
• Andreotti F, Testa L, Biondi-Zoccai GG, et al. Aspirin plus warfarin compared to aspirin alone after acute coronary syndromes: an updated and comprehensive meta-analysis of 25,307 patients. Eur Heart J 2006;27:519-26
   PubMed Web of Science ®Google Scholar
• Wells PS, Anderson DR, Bormanis J, et al. Value of assessment of pretest probability of deep-vein thrombosis in clinical management. Lancet 1997;350:1795-8
   PubMed Web of Science ®Google Scholar
• 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;105:557-63
   PubMed Web of Science ®Google Scholar
• Brouwer MA, van den Bergh PJ, Aengevaeren WR, 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;106:659-65
   PubMed Web of Science ®Google Scholar
• OASIS Investigators. Effects of long-term, moderate-intensity oral anticoagulation in addition to aspirin in unstable angina. The Organization to Assess Strategies for Ischemic Syndromes (OASIS) Investigators. J Am Coll Cardiol 2001;37:475-84
   PubMedGoogle Scholar
• Karjalainen PP, Porela P, Ylitalo A, et al. Safety and efficacy of combined antiplatelet–warfarin therapy after coronary stenting. Eur Heart J 2007;28:726-32
   PubMed Web of Science ®Google Scholar
• Holmes DR Jr, Kereiakes DJ, Kleiman NS, et al. Combining antiplatelet and anticoagulant therapies. J Am Coll Cardiol 2009;54:95-109
   PubMed Web of Science ®Google Scholar
• Ruiz-Nodar JM, Marín F, Hurtado JA, et al. Anticoagulant and antiplatelet therapy use in 426 patients with atrial fibrillation undergoing percutaneous coronary intervention and stent implantation: implications for bleeding risk and prognosis. J Am Coll Cardiol 2008;51:818-25
   PubMed Web of Science ®Google Scholar
• Kubitza D, Becka M, Wensing G, et al. Safety, pharmacodynamics, and pharmacokinetics of BAY 59-7939 – an oral, direct Factor Xa inhibitor – after multiple dosing in healthy male subjects. Eur J Clin Pharmacol 2005;61:873-80
   PubMed Web of Science ®Google Scholar
• Kubitza D, Becka M, Roth A, et al. Dose-escalation study of the pharmacokinetics and pharmacodynamics of rivaroxaban in healthy elderly subjects. Curr Med Res Opin 2008;24:2757-65
   PubMed Web of Science ®Google Scholar
• Raghavan N, Frost CE, Yu Z, et al. Apixaban metabolism and pharmacokinetics after oral administration to humans. Drug Metab Dispos 2009;37:74-81
   PubMed Web of Science ®Google Scholar
• Pinto DJ, Orwat MJ, Koch S, et al. Discovery of 1-(4-Methoxyphenyl)-7-oxo-6-(4-(2-oxopiperidin-1-yl)phenyl)-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide (apixaban, BMS-562247), a highly potent, selective, efficacious, and orally bioavailable inhibitor of blood coagulation Factor Xa. J Med Chem 2007;50:5339-56
   PubMed Web of Science ®Google Scholar
• Weitz JI, Cao C, Eriksson BI, et al. A dose-finding study with TAK-442, an oral factor Xa inhibitor, in patients undergoing elective total knee replacement surgery. Thromb Haemost 2010;104:1150-7
   PubMed Web of Science ®Google Scholar
• Stangier J, Clemens A. Pharmacology, pharmacokinetics, and pharmacodynamics of dabigatran etexilate, an oral direct thrombin inhibitor. Clin Appl Thromb Hemost 2009;15(Suppl 1):9-16S
   PubMed Web of Science ®Google Scholar
• Blech S, Ebner T, Ludwig-Schwellinger E, et al. The metabolism and disposition of the oral direct thrombin inhibitor, dabigatran, in humans. Drug Metab Dispos 2008;36:386-99
   PubMed Web of Science ®Google Scholar
• Weitz JI. New anticoagulants for treatment of venous thromboembolism. Circulation 2004;110:I19-26
   PubMed Web of Science ®Google Scholar
• Wallentin L, Wilcox RG, Weaver WD, et al. Oral ximelagatran for secondary prophylaxis after myocardial infarction: the ESTEEM randomised controlled trial. Lancet 2003;362:789-97
   PubMed Web of Science ®Google Scholar
• AstraZeneca decides to withdraw Exanta. AstraZeneca, 2006. Available at: http://www.astrazeneca.com/Media/Press-releases/Article/20060214-AstraZeneca-Decides-to-Withdraw-Exanta [Last accessed 6 March 2014]
   Google Scholar
• Eriksson BI, Quinlan DJ, Weitz JI. Comparative pharmacodynamics and pharmacokinetics of oral direct thrombin and Factor Xa inhibitors in development. Clin Pharmacokinet 2009;48:1-22
   PubMed Web of Science ®Google Scholar
• Oldgren J, Budaj A, Granger CB, et al. Dabigatran vs. placebo in patients with acute coronary syndromes on dual antiplatelet therapy: a randomized, double-blind, phase II trial. Eur Heart J 2011;32:2781-9
   PubMed Web of Science ®Google Scholar
• Mega JL, Braunwald E, Wiviott SD, et al. Rivaroxaban in patients with a recent acute coronary syndrome. N Engl J Med 2012;366:9-19
   PubMed Web of Science ®Google Scholar
• Alexander JH, Lopes RD, James S, et al. Apixaban with antiplatelet therapy after acute coronary syndrome. N Engl J Med 2011;365:699-708
   PubMed Web of Science ®Google Scholar
• Goldstein S, Bates ER, Bhatt DL, et al. Phase 2 study of TAK-442, an oral factor Xa inhibitor, in patients following acute coronary syndrome. Thromb Haemost 2014;111:1141-52
   PubMed Web of Science ®Google Scholar
• Alexander JH, Becker RC, Bhatt DL, et al. Apixaban, an oral, direct, selective factor Xa inhibitor, in combination with antiplatelet therapy after acute coronary syndrome: results of the Apixaban for Prevention of Acute Ischemic and Safety Events (APPRAISE) trial. Circulation 2009;119:2877-85
   PubMed Web of Science ®Google Scholar
• Astellas Pharma Inc. discontinues development of darexaban (YM150), an oral direct Factor Xa inhibitor. Astellas Pharma Inc, 2011. Available at: http://www.astellas.com/en/corporate/news/detail/astellas-pharma-inc-discontinu.html [Last accessed 27 November 2013]
   Google Scholar
• Perzborn E, Roehrig S, Straub A, et al. The discovery and development of rivaroxaban, an oral, direct Factor Xa inhibitor. Nat Rev Drug Discov 2011;10:61-75
   PubMed Web of Science ®Google Scholar
• Mega JL, Braunwald E, Mohanavelu S, et al. Rivaroxaban versus placebo in patients with acute coronary syndromes (ATLAS ACS-TIMI 46): a randomised, double-blind, phase II trial. Lancet 2009;374:29-38
   PubMed Web of Science ®Google Scholar
• Mega JL, Braunwald E, Wiviott SD, et al. Comparison of the efficacy and safety of two rivaroxaban doses in acute coronary syndrome (from ATLAS ACS 2-TIMI 51). Am J Cardiol 2013;112:472-8
   PubMed Web of Science ®Google Scholar
• Gibson CM, Chakrabarti AK, Mega JL, et al. Reduction of stent thrombosis in patients with acute coronary syndrome treated with rivaroxaban in ATLAS ACS 2-TIMI 51. J Am Coll Cardiol 2013;62:286-90
   PubMed Web of Science ®Google Scholar
• Miller R. Missing data lead FDA panel to vote against rivaroxaban for ACS. 2012. Available at: http://www.theheart.org/article/1405663.do [Last accessed 1 August 2013]
   Google Scholar
• Wood S. Again, FDA advisors deliver solid ‘no’ to rivaroxaban in ACS. 2014. Available at: http://www.medscape.com/viewarticle/819318 [Last accessed 27 January 2014]
   Google Scholar
• Bayer Pharma AG. Xarelto (rivaroxaban) Summary of Product Characteristics. 2013. Available at: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000944/WC500057108.pdf [Last accessed 19 June 2014]
   Google Scholar
• Boehringer Ingelheim International GmbH. Pradaxa (dabigatran etexilate) Summary of Product Characteristics. 2013. Available at: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000829/WC500041059.pdf [Last accessed 2 May 2014]
   Google Scholar
• Bristol-Myers Squibb, Pfizer EEIG. Eliquis (apixaban) Summary of Product Characteristics. 2013. Available at: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002148/WC500107728.pdf [Last accessed 19 June 2014]
   Google Scholar
• Montalescot G, Wiviott SD, Braunwald E, et al. Prasugrel compared with clopidogrel in patients undergoing percutaneous coronary intervention for ST-elevation myocardial infarction (TRITON-TIMI 38): double-blind, randomised controlled trial. Lancet 2009;373:723-31
   PubMed Web of Science ®Google Scholar
• Eriksson BI, Borris LC, Friedman RJ, et al. Rivaroxaban versus enoxaparin for thromboprophylaxis after hip arthroplasty. N Engl J Med 2008;358:2765-75
   PubMed Web of Science ®Google Scholar
• Kakkar AK, Brenner B, Dahl OE, et al. Extended duration rivaroxaban versus short-term enoxaparin for the prevention of venous thromboembolism after total hip arthroplasty: a double-blind, randomised controlled trial. Lancet 2008;372:31-9
   PubMed Web of Science ®Google Scholar
• Lassen MR, Ageno W, Borris LC, et al. Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty. N Engl J Med 2008;358:2776-86
   PubMed Web of Science ®Google Scholar
• Turpie AGG, Lassen MR, Davidson BL, et al. Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty (RECORD4): a randomised trial. Lancet 2009;373:1673-80
   PubMed Web of Science ®Google Scholar
• The EINSTEIN Investigators. Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med 2010;363:2499-510
   PubMed Web of Science ®Google Scholar
• The EINSTEIN–PE Investigators. Oral rivaroxaban for the treatment of symptomatic pulmonary embolism. N Engl J Med 2012;366:1287-97
   PubMed Web of Science ®Google Scholar
• Patel MR, Mahaffey KW, Garg J, et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med 2011;365:883-91
   PubMed Web of Science ®Google Scholar
• Roe MT, Ohman EM. A new era in secondary prevention after acute coronary syndrome. N Engl J Med 2012;366:85-7
   PubMed Web of Science ®Google Scholar
• Slides for the January 16, 2014 meeting of the CRDAC. FDA Cardiovascular and Renal Drugs Advisory Committee (CRDAC) meeting, 2014. Available at: http://www.fda.gov/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/CardiovascularandRenalDrugsAdvisoryCommittee/ucm386280.htm [Last accessed 8 July 2014]
   Google Scholar