Download PDF
Thromb Haemost 2010; 104(04): 657-663
DOI: 10.1160/TH10-05-0332
Clinical Focus
Schattauer GmbH

Atherothrombosis and atrial fibrillation: Important and often overlapping clinical syndromes

Jeremiah P. Depta
1   Division of Cardiology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA
,
Deepak L. Bhatt
2   VA Boston Healthcare System, Brigham and Women‘s Hospital, Harvard Medical School, Boston, Massachusetts, USA
› Author Affiliations
Further Information

Publication History

Received: 30 May 2010

Accepted after minor revision: 15 July 2010

Publication Date:
24 November 2017 (online)

    Permissions and Reprints

 

 

  • References

  • 1 Miyasaka Y, Barnes ME, Gersh BJ. et al. Secular trends in incidence of atrial fibrillation in Olmsted County, Minnesota, 1980 to 2000, and implications on the projections for future prevalence. Circulation 2006; 114: 119-125.
    CrossrefPubMedGoogle Scholar
  • 2 Lloyd-Jones D, Adams RJ, Brown TM. et al. Heart disease and stroke statistics--2010 update: a report from the American Heart Association. Circulation 2010; 121: e46-e215.
    CrossrefPubMedGoogle Scholar
  • 3 Goto S, Bhatt DL, Rother J. et al. Prevalence, clinical profile, and cardiovascular outcomes of atrial fibrillation patients with atherothrombosis. Am Heart J 2008; 156: 855-863e2.
    CrossrefPubMedGoogle Scholar
  • 4 Feinberg WM, Blackshear JL, Laupacis A. et al. Prevalence, age distribution, and gender of patients with atrial fibrillation. Analysis and implications. Arch Intern Med 1995; 155: 469-473.
    CrossrefPubMedGoogle Scholar
  • 5 Fuster V, Moreno PR, Fayad ZA. et al. Atherothrombosis and high-risk plaque: part I: evolving concepts. J Am Coll Cardiol 2005; 46: 937-954.
    CrossrefPubMedGoogle Scholar
  • 6 Watson T, Shantsila E, Lip GY. Mechanisms of thrombogenesis in atrial fibrillation: Virchow’s triad revisited. Lancet 2009; 373: 155-166.
    CrossrefPubMedGoogle Scholar
  • 7 Bhatt DL, Topol EJ. Need to test the arterial inflammation hypothesis. Circulation 2002; 106: 136-140.
    CrossrefPubMedGoogle Scholar
  • 8 Blake GJ, Ridker PM. C-reactive protein and other inflammatory risk markers in acute coronary syndromes. J Am Coll Cardiol 2003; 41: 37S-42S.
    CrossrefPubMedGoogle Scholar
  • 9 Boos CJ, Lip GY. The role of inflammation in atrial fibrillation. Int J Clin Pract 2005; 59: 870-872.
    CrossrefPubMedGoogle Scholar
  • 10 Boos CJ, Anderson RA, Lip GY. Is atrial fibrillation an inflammatory disorder?. Eur Heart J 2006; 27: 136-149.
    CrossrefPubMedGoogle Scholar
  • 11 Thambidorai SK, Parakh K, Martin DO. et al. Relation of C-reactive protein correlates with risk of thromboembolism in patients with atrial fibrillation. Am J Cardiol 2004; 94: 805-807.
    CrossrefPubMedGoogle Scholar
  • 12 Conway DS, Buggins P, Hughes E. et al. Prognostic significance of raised plasma levels of interleukin-6 and C-reactive protein in atrial fibrillation. Am Heart J 2004; 148: 462-466.
    CrossrefPubMedGoogle Scholar
  • 13 Conway DS, Buggins P, Hughes E. et al. Relationship of interleukin-6 and C-reactive protein to the prothrombotic state in chronic atrial fibrillation. J Am Coll Cardiol 2004; 43: 2075-2082.
    CrossrefPubMedGoogle Scholar
  • 14 Roldan V, Marin F, Blann AD. et al. Interleukin-6, endothelial activation and thrombogenesis in chronic atrial fibrillation. Eur Heart J 2003; 24: 1373-1380.
    CrossrefPubMedGoogle Scholar
  • 15 Depta JP, Bhatt DL. Aspirin and platelet adenosine diphosphate receptor antagonists in acute coronary syndromes and percutaneous coronary intervention: role in therapy and strategies to overcome resistance. Am J Cardiovasc Drugs 2008; 8: 91-112.
    CrossrefPubMedGoogle Scholar
  • 16 Becker RC. Understanding the dynamics of thrombin in cardiovascular disease: pathobiology and biochemistry for the clinician. Am Heart J 2005; 149: S2-8.
    CrossrefPubMedGoogle Scholar
  • 17 Krishnamoorthy S, Lim SH, Lip GY. Assessment of endothelial (dys)function in atrial fibrillation. Ann Med 2009; 41: 576-590.
    CrossrefPubMedGoogle Scholar
  • 18 Li-Saw-Hee FL, Blann AD, Gurney D. et al. Plasma von Willebrand factor, fibrinogen and soluble P-selectin levels in paroxysmal, persistent and permanent atrial fibrillation. Effects of cardioversion and return of left atrial function. Eur Heart J 2001; 22: 1741-1747.
    CrossrefPubMedGoogle Scholar
  • 19 Marin F, Roldan V, Climent VE. et al. Plasma von Willebrand factor, soluble thrombomodulin, and fibrin D-dimer concentrations in acute onset non-rheumatic atrial fibrillation. Heart 2004; 90: 1162-1166.
    CrossrefPubMedGoogle Scholar
  • 20 Goto S, Sakai H, Goto M. et al. Enhanced shear-induced platelet aggregation in acute myocardial infarction. Circulation 1999; 99: 608-613.
    CrossrefPubMedGoogle Scholar
  • 21 Sakai H, Goto S, Kim JY. Plasma concentration of von Willebrand factor in acute myocardial infarction. Thromb Haemost 2000; 84: 204-209.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 22 Bhatt DL, Topol EJ. Scientific and therapeutic advances in antiplatelet therapy. Nat Rev Drug Discov 2003; 2: 15-28.
    CrossrefPubMedGoogle Scholar
  • 23 Kamath S, Chin BS, Blann AD. et al. A study of platelet activation in paroxysmal, persistent and permanent atrial fibrillation. Blood Coagul Fibrinol 2002; 13: 627-636.
    CrossrefPubMedGoogle Scholar
  • 24 Choudhury A, Chung I, Blann A. et al. Platelet adhesion in atrial fibrillation. Thromb Res 2007; 120: 623-629.
    CrossrefPubMedGoogle Scholar
  • 25 Sohara H, Amitani S, Kurose M. et al. Atrial fibrillation activates platelets and coagulation in a time-dependent manner: a study in patients with paroxysmal atrial fibrillation. J Am Coll Cardiol 1997; 29: 106-112.
    CrossrefPubMedGoogle Scholar
  • 26 Choudhury A, Chung I, Blann AD. et al. Elevated platelet microparticle levels in nonvalvular atrial fibrillation: relationship to p-selectin and antithrombotic therapy. Chest 2007; 131: 809-815.
    CrossrefPubMedGoogle Scholar
  • 27 Azzam H, Zagloul M. Elevated platelet microparticle levels in valvular atrial fibrillation. Hematol 2009; 14: 357-360.
    PubMedGoogle Scholar
  • 28 Duygu H, Barisik V, Kurt H. et al. Prognostic value of plasma soluble CD40 ligand in patients with chronic non-valvular atrial fibrillation. Europace 2008; 10: 210-214.
    CrossrefPubMedGoogle Scholar
  • 29 Becker RC. Biomarkers in atrial fibrillation: investigating biologic plausibility, cause, and effect. J Thromb Thrombolysis 2005; 19: 71-75.
    CrossrefPubMedGoogle Scholar
  • 30 Stritzke J, Markus MR, Duderstadt S. et al. The aging process of the heart: obesity is the main risk factor for left atrial enlargement during aging the MONICA/ KORA (monitoring of trends and determinations in cardiovascular disease/cooperative research in the region of Augsburg) study. J Am Coll Cardiol 2009; 54: 1982-1989.
    CrossrefPubMedGoogle Scholar
  • 31 Go AS, Hylek EM, Phillips KA. et al. Prevalence of diagnosed atrial fibrillation in adults: national implications for rhythm management and stroke prevention: the AnTicoagulation and Risk Factors in Atrial Fibrillation (ATRIA) Study. J Am Med Assoc 2001; 285: 2370-2375.
    CrossrefPubMedGoogle Scholar
  • 32 Lavie CJ, Milani RV, Ventura HO. Obesity and cardiovascular disease: risk factor, paradox, and impact of weight loss. J Am Coll Cardiol 2009; 53: 1925-1932.
    CrossrefPubMedGoogle Scholar
  • 33 Wanahita N, Messerli FH, Bangalore S. et al. Atrial fibrillation and obesity--results of a meta-analysis. Am Heart J 2008; 155: 310-315.
    CrossrefPubMedGoogle Scholar
  • 34 Tedrow UB, Conen D, Ridker PM. et al. The long- and short-term impact of elevated body mass index on the risk of new atrial fibrillation: The WHS (Women’s Health Study). J Am Coll Cardiol 2010; 55: 2319-2327.
    CrossrefPubMedGoogle Scholar
  • 35 Bhatt DL, Steg PG, Ohman EM. et al. International prevalence, recognition, and treatment of cardiovascular risk factors in outpatients with atherothrombosis. J Am Med Assoc 2006; 295: 180-189.
    CrossrefPubMedGoogle Scholar
  • 36 Steg PG, Bhatt DL, Wilson PW. et al. One-year cardiovascular event rates in out-patients with atherothrombosis. J Am Med Assoc 2007; 297: 1197-1206.
    CrossrefPubMedGoogle Scholar
  • 37 Singer DE, Albers GW, Dalen JE. et al. Antithrombotic therapy in atrial fibrillation: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008; 133: 546S-592S.
    CrossrefPubMedGoogle Scholar
  • 38 Lip GY, Karpha M. Anticoagulant and antiplatelet therapy use in patients with atrial fibrillation undergoing percutaneous coronary intervention: the need for consensus and a management guideline. Chest 2006; 130: 1823-1827.
    CrossrefPubMedGoogle Scholar
  • 39 Nieuwlaat R, Capucci A, Lip GY. et al. Antithrombotic treatment in real-life atrial fibrillation patients: a report from the Euro Heart Survey on Atrial Fibrillation. Eur Heart J 2006; 27: 3018-3026.
    CrossrefPubMedGoogle Scholar
  • 40 Depta JP, Cannon CP, Fonarow GC. et al. Patient characteristics associated with the choice of triple antithrombotic therapy in acute coronary syndromes. Am J Cardiol 2009; 104: 1171-1178.
    CrossrefPubMedGoogle Scholar
  • 41 Tay KH, Lane DA, Lip GY. Bleeding risks with combination of oral anticoagulation plus antiplatelet therapy: is clopidogrel any safer than aspirin when combined with warfarin?. Thromb Haemost 2008; 100: 955-957.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 42 Kakar P, Lane D, Lip GY. Bleeding risk stratification models in deciding on anticoagulation in patients with atrial fibrillation: a useful complement to stroke risk stratification schema. Chest 2006; 130: 1296-1299.
    CrossrefPubMedGoogle Scholar
  • 43 Somme D, Corvol A, Lazarovici C. et al. Clinical Usefulness in Geriatrics patients of Combining the CHADS2 and HEMORR2HAGES Scores for Guiding Anti-thrombotic Prophylaxis in Atrial Fibrillation. A preliminary study. Aging Clin Exp Res. 2009 Epub ahead of print.
    PubMedGoogle Scholar
  • 44 Hylek EM, Evans-Molina C, Shea C. et al. Major hemorrhage and tolerability of warfarin in the first year of therapy among elderly patients with atrial fibrillation. Circulation 2007; 115: 2689-2696.
    CrossrefPubMedGoogle Scholar
  • 45 Levi M, Hovingh K. Bleeding complications in patients on anticoagulants who would have been disqualified for clinical trials. Thromb Haemost 2008; 100: 1047-1051.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 46 Gladstone DJ, Bui E, Fang J. et al. Potentially preventable strokes in high-risk patients with atrial fibrillation who are not adequately anticoagulated. Stroke 2009; 40: 235-240.
    CrossrefPubMedGoogle Scholar
  • 47 Singer DE, Chang Y, Fang MC. et al. The net clinical benefit of warfarin anticoagulation in atrial fibrillation. Ann Intern Med 2009; 151: 297-305.
    CrossrefPubMedGoogle Scholar
  • 48 Gage BF, Waterman AD, Shannon W. et al. Validation of clinical classification schemes for predicting stroke: results from the National Registry of Atrial Fibrillation. J Am Med Assoc 2001; 285: 2864-2870.
    CrossrefPubMedGoogle Scholar
  • 49 Gage BF, van Walraven C, Pearce L. et al. Selecting patients with atrial fibrillation for anticoagulation: stroke risk stratification in patients taking aspirin. Circulation 2004; 110: 2287-2292.
    CrossrefPubMedGoogle Scholar
  • 50 Connolly S, Pogue J, Hart R. et al. Clopidogrel plus aspirin versus oral anticoagulation for atrial fibrillation in the Atrial fibrillation Clopidogrel Trial with Irbesartan for prevention of Vascular Events (ACTIVE W): a randomised controlled trial. Lancet 2006; 367: 1903-1912.
    CrossrefPubMedGoogle Scholar
  • 51 Connolly SJ, Pogue J, Eikelboom J. et al. Benefit of oral anticoagulant over antiplatelet therapy in atrial fibrillation depends on the quality of international normalized ratio control achieved by centers and countries as measured by time in therapeutic range. Circulation 2008; 118: 2029-2037.
    CrossrefPubMedGoogle Scholar
  • 52 Lip GY, Nieuwlaat R, Pisters R. et al. Refining clinical risk stratification for predicting stroke and thromboembolism in atrial fibrillation using a novel risk factor-based approach: the euro heart survey on atrial fibrillation. Chest 2010; 137: 263-272.
    CrossrefPubMedGoogle Scholar
  • 53 Lip GY. Paroxysmal atrial fibrillation, stroke risk and thromboprophylaxis. Thromb Haemost 2008; 100: 11-13.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 54 Karthikeyan G, Eikelboom JW. The CHADS2 score for stroke risk stratification in atrial fibrillation--friend or foe?. Thromb Haemost 2010; 104: 45-48.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 55 Lip GY. Anticoagulation therapy and the risk of stroke in patients with atrial fibrillation at ‘moderate risk’ [CHADS2 score=1]: simplifying stroke risk assessment and thromboprophylaxis in real-life clinical practice. Thromb Haemost 2010; 103: 683-685.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 56 Healey JS, Hart RG, Pogue J. et al. Risks and benefits of oral anticoagulation compared with clopidogrel plus aspirin in patients with atrial fibrillation according to stroke risk: the atrial fibrillation clopidogrel trial with irbesartan for prevention of vascular events (ACTIVE-W). Stroke 2008; 39: 1482-1486.
    CrossrefPubMedGoogle Scholar
  • 57 Gorin L, Fauchier L, Nonin E. et al. Antithrombotic treatment and the risk of death and stroke in patients with atrial fibrillation and a CHADS2 score=1. Thromb Haemost 2010; 103: 833-840.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 58 Hylek EM, D’Antonio J, Evans-Molina C. et al. Translating the results of randomized trials into clinical practice: the challenge of warfarin candidacy among hospitalized elderly patients with atrial fibrillation. Stroke 2006; 37: 1075-1080.
    CrossrefPubMedGoogle Scholar
  • 59 Pradhan AA, Levine MA. Warfarin use in atrial fibrillation: A random sample survey of family physician beliefs and preferences. Can J Clin Pharmacol 2002; 9: 199-202.
    PubMedGoogle Scholar
  • 60 Gage BF, Boechler M, Doggette AL. et al. Adverse outcomes and predictors of underuse of antithrombotic therapy in medicare beneficiaries with chronic atrial fibrillation. Stroke 2000; 31: 822-827.
    CrossrefPubMedGoogle Scholar
  • 61 Mant J, Hobbs FD, Fletcher K. et al. Warfarin versus aspirin for stroke prevention in an elderly community population with atrial fibrillation (the Birmingham Atrial Fibrillation Treatment of the Aged Study, BAFTA): a randomised controlled trial. Lancet 2007; 370: 493-503.
    CrossrefPubMedGoogle Scholar
  • 62 Pengo V, Cucchini U, Denas G. et al. Lower versus standard intensity oral anticoagulant therapy (OAT) in elderly warfarin-experienced patients with non-valvular atrial fibrillation. Thromb Haemost 2010; 103: 442-449.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 63 Adjusted-dose warfarin versus low-intensity, fixed-dose warfarin plus aspirin for high-risk patients with atrial fibrillation: Stroke Prevention in Atrial Fibrillation III randomised clinical trial. Lancet 1996; 348: 633-638.
    CrossrefPubMedGoogle Scholar
  • 64 Garwood CL, Corbett TL. Use of anticoagulation in elderly patients with atrial fibrillation who are at risk for falls. Ann Pharmacother 2008; 42: 523-532.
    CrossrefPubMedGoogle Scholar
  • 65 Man-Son-Hing M, Nichol G, Lau A. et al. Choosing antithrombotic therapy for elderly patients with atrial fibrillation who are at risk for falls. Arch Intern Med 1999; 159: 677-685.
    CrossrefPubMedGoogle Scholar
  • 66 Connolly SJ, Pogue J, Hart RG, Hohnloser SH, Pfeffer M. et al. Effect of clopidogrel added to aspirin in patients with atrial fibrillation. N Engl J Med 2009; 360: 2066-2078.
    CrossrefPubMedGoogle Scholar
  • 67 Rubboli A, Halperin JL. Pro: ‘Antithrombotic therapy with warfarin, aspirin and clopidogrel is the recommended regime in anticoagulated patients who present with an acute coronary syndrome and/or undergo percutaneous coronary interventions‘. Thromb Haemost 2008; 100: 752-753.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 68 Roldán V, Marín F. Contra: ‘Antithrombotic therapy with warfarin, aspirin and clopidogrel is the recommended regimen in anticoagulated patients who present with an acute coronary syndrome and/or undergo percutaneous coronary interventions‘. Not for everybody. Thromb Haemost 2008; 100: 754-755.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 69 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. J Am Coll Cardiol 2007; 50: e1-e157.
    CrossrefPubMedGoogle Scholar
  • 70 Lip GY, Huber K, Andreotti F. et al. Management of antithrombotic therapy in atrial fibrillation patients presenting with acute coronary syndrome and/or undergoing percutaneous coronary intervention/ stenting. Thromb Haemost 2010; 103: 13-28.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 71 Holmes DR, Reddy VY, Turi ZG. et al. Percutaneous closure of the left atrial appendage versus warfarin therapy for prevention of stroke in patients with atrial fibrillation: a randomised non-inferiority trial. Lancet 2009; 374: 534-542.
    CrossrefPubMedGoogle Scholar
  • 72 Wrigley BJ, Lip GY. Can the WATCHMAN device truly PROTECT from stroke in atrial fibrillation?. Lancet Neurol 2009; 8: 877-878.
    CrossrefPubMedGoogle Scholar
  • 73 Eikelboom JW, Weitz JI. Another oral thrombin inhibitor for stroke prevention-in atrial fibrillation?. Thromb Haemost 2010; 103: 481-483.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 74 Eikelboom JW, Weitz JI. New anticoagulants. Circulation 2010; 121: 1523-1532.
    CrossrefPubMedGoogle Scholar
  • 75 Connolly SJ, Ezekowitz MD, Yusuf S. et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 2009; 36: 1139-1151.
    PubMedGoogle Scholar
  • 76 Randomized dabigatran etexilate dose finding study with acute coronary syndromes post index event with additional risk factors for cardiovascular complication also receiving aspirin and clopidogrel: RE-DEEM. Presented at the 82nd Annual Scientific Sessions of the American heart Association; 2009 Nov 14–18; Orlando, FL.
    PubMedGoogle Scholar
  • 77 Lip GY, Rasmussen LH, Olsson SB. et al. Oral direct thrombin inhibitor AZD0837 for the prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation: a randomized dose-guiding, safety, and tolerability study of four doses of AZD0837 vs. vitamin K antagonists. Eur Heart J 2009; 30: 2897-2907.
    CrossrefPubMedGoogle Scholar
  • 78 Olsson SB, Rasmussen LH, Tveit A. et al. Safety and tolerability of an immediate-release formulation of theoral direct thrombin inhibitor AZD0837 in the prevention of stroke and systemic embolism in patients with atrial fibrillation. Thromb Haemost 2010; 103: 604-612.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 79 Clinicaltrials.gov.. A Phase 3, Active (Warfarin) Controlled, Randomized, Double-Blind, Parallel Arm Study to Evaluate Efficacy and Safety of Apixaban in Preventing Stroke and Systemic Embolism in Subjects With Nonvalvular Atrial Fibrillation (ARISTOTLE). Available at: http://clinicaltrials.gov/ct2/show/NCT00412984?term=apixaban&rank=7. Accessed May 20, 2010.
    PubMedGoogle Scholar
  • 80 Clinicaltrials.gov.. Apixaban Versus Acetylsalicylic Acid (ASA) to Prevent Stroke in Atrial Fibrillation Patients Who Have Failed or Are Unsuitable for Vitamin K Antagonist Treatment: A Randomized Double Blind Trial (AVERROES). Available at: http://clinicaltrials.gov/ct2/show/NCT00496769. Accessed May 20, 2010.
    PubMedGoogle Scholar
  • 81 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: 2877-2885.
    CrossrefPubMedGoogle Scholar
  • 82 Clinicaltrials.gov.. Apixaban for Prevention of Acute Ischemic Events – 2 A Phase 3, Randomized, Double-Blind, Evaluation of the Safety and Efficacy of Apixaban In Subjects With a Recent Acute Coronary Syndrome (APPRAISE-2). Available at: http://clinicaltrials.gov/ct2/show/NCT00831441?term=apixaban&rank=16. Accessed May 20, 2010.
    PubMedGoogle Scholar
  • 83 Clinicaltrials.gov.. A Phase 3, Randomized, Double-Blind, Double-Dummy, Parallel Group, Multi-Center, Multi-National Study for Evaluation of Efficacy and Safety of DU-176b Versus Warfarin In Subjects With Atrial Fibrillation – Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation (ENGAGE – AF TIMI – 48). Available at: http://clinicaltrials.gov/ct2/show/NCT00781391. Accessed May 20, 2010.
    PubMedGoogle Scholar
  • 84 ROCKET AF Study Investigators.. Rivaroxaban-once daily, oral, direct factor Xa inhibition compared with vitamin K antagonism for prevention of stroke and Embolism Trial in Atrial Fibrillation: rationale and design of the ROCKET AF study. Am Heart J 2010; 159: 340-347.e1.
    CrossrefPubMedGoogle Scholar
  • 85 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.
    CrossrefPubMedGoogle Scholar
  • 86 Clinicaltrials.gov.. A Randomized, Double-Blind, Placebo-Controlled, Event-Driven Multicenter Study to Evaluate the Efficacy and Safety of Rivaroxaban in Subjects With a Recent Acute Coronary Syndrome. Available at: http://clinical-trials.gov/ct2/show/NCT00809965?term=Rivaroxaban&rank=9. Accessed May 29, 2010.
    PubMedGoogle Scholar
  • 87 Clinicaltrials.gov.. A Phase 2, Double-blind, Randomized, Placebo-controlled Study of the Safety and Efficacy of TAK-442 in Subjects With Acute Coronary Syndromes. Available at: http://clinicaltrials.gov/ct2/show/NCT00677053?term=TAK-442&rank=1. Accessed May 29, 2010.
    PubMedGoogle Scholar
  • 88 Rajagopal V, Bhatt DL. Factor Xa inhibitors is acute coronary syndromes: moving from mythology to reality. J Thromb Haemost 2005; 3: 436-438.
    CrossrefPubMedGoogle Scholar