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Thromb Haemost 2011; 106(01): 34-44
DOI: 10.1160/TH10-10-0674
Review Article
Schattauer GmbH

Ischaemic stroke and bleeding rates in ‘real-world’ atrial fibrillation patients

Isla M. Ogilvie
1   BioMedCom Consultants inc., Montréal, Canada
,
Sharon A. Welner
1   BioMedCom Consultants inc., Montréal, Canada
,
Warren Cowell
2   Global Health Economics and Reimbursement, Bayer HealthCare, Uxbridge, UK
,
Gregory Y. H. Lip
3   University of Birmingham Centre for Cardiovascular Sciences, City Hospital, Birmingham, UK
› Author Affiliations Financial support: This study was funded by Bayer Healthcare, UK.
Further Information

Publication History

Received: 25 October 2010

Accepted after major revision: 22 April 2011

Publication Date:
24 November 2017 (online)

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Summary

Stroke prevention guidelines recommend oral anticoagulants (OAC) for atrial fibrillation (AF) patients at moderate/high risk of stroke, and antiplatelet or no therapy for those at low/moderate risk. Outcomes for AF patients receiving antiplatelet/no therapy in ‘real-life’ clinical practice were explored. This study compared clinical event rates (stroke/bleeding) for AF patients treated with OAC therapy, antiplatelets or no therapy in usual clinical practice to event rates in OAC-treated AF patients from optimally-monitored ‘real-life’ settings (anticoagulation clinics). We searched biomedical literature (1994–2010) using PubMed to identify ‘real-world’ studies of clinical event rates for AF patients receiving OAC therapy, antiplatelets, or no therapy; event rates were extracted for each treatment and setting. We identified 136 studies of thromboembolic events and 86 of bleeding events. Ischaemic stroke rates (30 studies) were higher for AF patients receiving no therapy (median: 4.45/100 person-years; range: 0.25–5.9) or antiplatelet-therapy (median: 4.45/100 person-years; range: 2.0–10) compared to OACtreated patients monitored in anticoagulation clinics (median: 1.72/100 person-years; range: 0.97–2.00), or from a non-specialized setting (median 1.66/100 person-years; range: 0–4.9). Major bleeding rates (32 studies) for patients receiving antiplatelet/no therapy were similar to OAC-treated patients from both clinical settings. As in randomised clinical trials, AF patients in ‘real-world’ clinical practice receiving antiplatelet/no therapy have higher rates of ischaemic stroke than OAC-treated patients. Antiplatelet/no therapy was associated with similar bleeding rates to OAC therapy. Increasing utilisation of anticoagulants in clinical practice could improve patient outcomes.

Keywords

Atrial fibrillation - oral anticoagulation - antiplatelets - stroke - bleeding
 

  • References

  • 1 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
  • 2 Guize L, Thomas F, Bean K. et al. Atrial fibrillation: prevalence, risk factors and mortality in a large French population with 15 years of follow-up. Bull Acad Natl Med 2007; 191: 791-803.
    PubMedGoogle Scholar
  • 3 Friberg J, Scharling H, Gadsboll N. et al. Comparison of the impact of atrial fibrillation on the risk of stroke and cardiovascular death in women versus men (The Copenhagen City Heart Study). Am J Cardiol 2004; 94: 889-894.
    CrossrefPubMedGoogle Scholar
  • 4 Fang MC, Go AS, Chang Y. et al. Comparison of risk stratification schemes to predict thromboembolism in people with nonvalvular atrial fibrillation. J Am Coll Cardiol 2008; 51: 810-815.
    CrossrefPubMedGoogle Scholar
  • 5 Fuster V, Ryden LE, Cannom DS. et al. ACC/AHA/ESC 2006 Guidelines for the Management of Patients with Atrial Fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation): developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society. Circulation 2006; 114: e257-e354
    CrossrefPubMedGoogle Scholar
  • 6 Singer DE, Albers GW, Dalen JE. et al. Antithrombotic therapy in atrial fibrillation: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 2004; 126 (Suppl. 03) 429S-56S.
    CrossrefPubMedGoogle Scholar
  • 7 Goldstein LB, Adams R, Alberts MJ. et al. Primary prevention of ischaemic stroke: a guideline from the American Heart Association/American Stroke Association Stroke Council: cosponsored by the Atherosclerotic Peripheral Vascular Disease Interdisciplinary Working Group; Cardiovascular Nursing Council; Clinical Cardiology Council; Nutrition, Physical Activity, and Metabolism Council; and the Quality of Care and Outcomes Research Interdisciplinary Working Group. Circulation 2006; 113: e873-e923
    PubMedGoogle Scholar
  • 8 National Institute for Health and Clinical Excellence.. NICE clinical guideline 36- Atrial fibrillation: the management of atrial fibrillation.. London- UK: 2006
  • 9 Hankey GJ. Non-valvular atrial fibrillation and stroke prevention. National Blood Pressure Advisory Committee of the National Heart Foundation. Med J Aust 2001; 174: 234-239.
    PubMedGoogle Scholar
  • 10 Fang MC, Singer DE, Chang Y. et al. Gender differences in the risk of ischaemic stroke and peripheral embolism in atrial fibrillation: the AnTicoagulation and Risk factors In Atrial fibrillation (ATRIA) study. Circulation 2005; 112: 1687-1691.
    CrossrefPubMedGoogle Scholar
  • 11 Sam C, Massaro JM, D’Agostino RB. Sr. et al. Warfarin and aspirin use and the predictors of major bleeding complications in atrial fibrillation (the Framingham Heart Study). Am J Cardiol 2004; 94: 947-951.
    CrossrefPubMedGoogle Scholar
  • 12 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
  • 13 Connolly SJ, Eikelboom J, O’Donnell M. et al. Challenges of establishing new antithrombotic therapies in atrial fibrillation. Circulation 2007; 116: 449-455.
    CrossrefPubMedGoogle Scholar
  • 14 van Walraven C, Jennings A, Oake N. et al. Effect of study setting on anticoagulation control: a systematic review and metaregression. Chest 2006; 129: 1155-1166.
    CrossrefPubMedGoogle Scholar
  • 15 Baker WL, Cios DA, Sander SD. et al. Meta-analysis to assess the quality of warfarin control in atrial fibrillation patients in the United States. J Manag Care Pharm 2009; 15: 244-252.
    PubMedGoogle Scholar
  • 16 Dolan G, Smith LA, Collins S. et al. Effect of setting, monitoring intensity and patient experience on anticoagulation control: a systematic review and meta-analysis of the literature. Curr Med Res Opin 2008; 24: 1459-1472.
    CrossrefPubMedGoogle Scholar
  • 17 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
  • 18 Morgan CL, McEwan P, Tukiendorf A. et al. Warfarin treatment in patients with atrial fibrillation: Observing outcomes associated with varying levels of INR control. Thromb Res 2008; 124: 37-41.
    PubMedGoogle Scholar
  • 19 Wallentin L, Ezekowitz MD, Eikelboom J. et al. Efficacy and safety of dabigatran compared to warfarin at different levels of INR control for stroke prevention in 18,113 patients with atrial fibrillation in the RE-LY trial. 2009 http://www.clinicaltrialresults.org/_ . (Accessed 27 Nov 2009).
    PubMedGoogle Scholar
  • 20 White HD, Gruber M, Feyzi J. et al. Comparison of outcomes among patients randomized to warfarin therapy according to anticoagulant control: results from SPORTIF III and V. Arch Intern Med 2007; 167: 239-245.
    CrossrefPubMedGoogle Scholar
  • 21 Burton C, Isles C, Norrie J. et al. The safety and adequacy of antithrombotic therapy for atrial fibrillation: a regional cohort study. Br J Gen Pract 2006; 56: 697-702.
    PubMedGoogle Scholar
  • 22 Bordin P, Mazzone C, Pandullo C. et al. Morbidity and mortality in 229 elderly patients with nonrheumatic atrial fibrillation. A five-year follow-up. Ital Heart J 2003; 4: 537-543.
    PubMedGoogle Scholar
  • 23 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
  • 24 Abdelhafiz AH, Wheeldon NM. Results of an open-label, prospective study of anticoagulant therapy for atrial fibrillation in an outpatient anticoagulation clinic. Clin Ther 2004; 26: 1470-1478.
    CrossrefPubMedGoogle Scholar
  • 25 Pengo V, Legnani C, Noventa F. et al. Oral anticoagulant therapy in patients with nonrheumatic atrial fibrillation and risk of bleeding. A Multicenter Inception Cohort Study. Thromb Haemost 2001; 85: 418-422.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 26 Hughes M, Lip GY. Risk factors for anticoagulation-related bleeding complications in patients with atrial fibrillation: a systematic review. QJM 2007; 100: 599-607.
    CrossrefPubMedGoogle Scholar
  • 27 Masaki N, Suzuki M, Matsumura A. et al. Quality of warfarin control affects the incidence of stroke in elderly patients with atrial fibrillation. Intern Med 2010; 49: 1711-1716.
    CrossrefPubMedGoogle Scholar
  • 28 Rose AJ, Ozonoff A, Henault LE. et al. Warfarin for atrial fibrillation in community-based practise. J Thromb Haemost 2008; 6: 1647-1654.
    CrossrefPubMedGoogle Scholar
  • 29 Poli D, Antonucci E, Marcucci R. et al. The quality of anticoagulation on functional outcome and mortality for TIA/stroke in atrial fibrillation patients. Int J Cardiol 2009; 132: 109-113.
    CrossrefPubMedGoogle Scholar
  • 30 Poli D, Antonucci E, Marcucci R. et al. Risk of bleeding in very old atrial fibrillation patients on warfarin: Relationship with ageing and CHADS(2) score. Thromb Res 2007; 121: 347-352.
    CrossrefPubMedGoogle Scholar
  • 31 Poli D, Antonucci E, Grifoni E. et al. Bleeding risk during oral anticoagulation in atrial fibrillation patients older than 80 years. J Am Coll Cardiol 2009; 54: 999-1002.
    CrossrefPubMedGoogle Scholar
  • 32 Parkash R, Wee V, Gardner MJ. et al. The impact of warfarin use on clinical outcomes in atrial fibrillation: a population-based study. Can J Cardiol 2007; 23: 457-461.
    CrossrefPubMedGoogle Scholar
  • 33 Torn M, Bollen WL, van der Meer FJ, van der Wall EE, Rosendaal FR. Risks of oral anticoagulant therapy with increasing age. Arch Intern Med 2005; 165: 1527-1532.
    CrossrefPubMedGoogle Scholar
  • 34 Nieuwlaat R, Olsson SB, Lip GY. et al. Guideline-adherent antithrombotic treatment is associated with improved outcomes compared with undertreatment in high-risk patients with atrial fibrillation. The Euro Heart Survey on Atrial Fibrillation. Am Heart J 2007; 153: 1006-1012.
    CrossrefPubMedGoogle Scholar
  • 35 Lewis WR, Fonarow GC, LaBresh KA. et al. Differential use of warfarin for secondary stroke prevention in patients with various types of atrial fibrillation. Am J Cardiol 2009; 103: 227-231.
    CrossrefPubMedGoogle Scholar
  • 36 Hylek EM, Go AS, Chang Y. et al. Effect of intensity of oral anticoagulation on stroke severity and mortality in atrial fibrillation. N Engl J Med 2003; 349: 1019-1026.
    CrossrefPubMedGoogle Scholar
  • 37 Aguilar M, Hart R, Pearce L. Oral anticoagulants versus antiplatelet therapy for preventing stroke in patients with non-valvular atrial fibrillation and no history of stroke or transient ischaemic attacks. Cochrane Database Syst Rev 2007; 3: CD006186
    PubMedGoogle Scholar
  • 38 Rash A, Downes T, Portner R. et al. A randomised controlled trial of warfarin versus aspirin for stroke prevention in octogenarians with atrial fibrillation (WASPO). Age Ageing 2007; 36: 151-156.
    CrossrefPubMedGoogle Scholar
  • 39 Ryan F, Byrne S, O’Shea S. Randomized controlled trial of supervised patient selftesting of warfarin therapy using an internet-based expert system. J Thromb Haemost 2009; 7: 1284-1290.
    CrossrefPubMedGoogle Scholar
  • 40 Dahri K, Loewen P. The risk of bleeding with warfarin: a systematic review and performance analysis of clinical prediction rules. Thromb Haemost 2007; 98: 980-987.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 41 Palareti G, Cosmi B. Bleeding with anticoagulation therapy - who is at risk, and how best to identify such patients. Thromb Haemost 2009; 102: 268-278.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 42 Gage BF, Yan Y, Milligan PE, Waterman AD, Culverhouse R, Rich MW. et al. Clinical classification schemes for predicting hemorrhage: results from the National Registry of Atrial Fibrillation (NRAF). Am Heart J 2006; 151: 713-719.
    CrossrefPubMedGoogle Scholar
  • 43 Tay KH, Lip GY, Lane DA. Atrial fibrillation and stroke risk prevention in real-life clinical practice. Thromb Haemost 2009; 101: 415-416.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 44 Poli D, Antonucci E, Grifoni E. et al. Stroke risk in atrial fibrillation patients on warfarin. Predictive ability of risk stratification schemes for primary and secondary prevention. Thromb Haemost 2009; 101: 367-372.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 45 Frykman V, Beerman B, Ryden L, Rosenqvist M. Management of atrial fibrillation: discrepancy between guideline recommendations and actual practice exposes patients to risk for complications. Eur Heart J 2001; 22: 1954-1959.
    CrossrefPubMedGoogle Scholar
  • 46 Kalra L, Yu G, Perez I, Lakhani A. et al. Prospective cohort study to determine if trial efficacy of anticoagulation for stroke prevention in atrial fibrillation translates into clinical effectiveness. Br Med J 2000; 320: 1236-1239.
    CrossrefPubMedGoogle Scholar
  • 47 Bravata DM, Rosenbeck K, Kancir S. et al. The use of warfarin in veterans with atrial fibrillation. BMC Cardiovasc Disord 2004; 4: 18
    CrossrefPubMedGoogle Scholar
  • 48 Go AS, Hylek EM, Borowsky LH. et al. Warfarin use among ambulatory patients with nonvalvular atrial fibrillation: the anticoagulation and risk factors in atrial fibrillation (ATRIA) study. Ann Intern Med 1999; 131: 927-934.
    PubMedGoogle Scholar
  • 49 Anderson N, Fuller R, Dudley N. ‘Rules of thumb’ or reflective practice? Understanding senior physicians’ decision-making about anti-thrombotic usage in atrial fibrillation. QJM 2007; 100: 263-269.
    CrossrefPubMedGoogle Scholar
  • 50 Gattellari M, Worthington J, Zwar N. et al. Barriers to the use of anticoagulation for nonvalvular atrial fibrillation: a representative survey of Australian family physicians. Stroke 2008; 39: 227-230.
    CrossrefPubMedGoogle Scholar
  • 51 Ageno W, Ambrosini F, Nardo B. et al. Atrial fibrillation and antithrombotic treatment in Italian hospitalized patients: a prospective, observational study. J Thromb Thrombolysis 2001; 12: 225-230.
    CrossrefPubMedGoogle Scholar
  • 52 Caro JJ, Flegel KM, Orejuela ME. et al. Anticoagulant prophylaxis against stroke in atrial fibrillation: effectiveness in actual practice. CMAJ 1999; 161: 493-497.
    PubMedGoogle Scholar
  • 53 Currie CJ, Jones M, Goodfellow J. et al. Evaluation of survival and ischaemic and thromboembolic event rates in patients with non-valvar atrial fibrillation in the general population when treated and untreated with warfarin. Heart 2006; 92: 196-200.
    CrossrefPubMedGoogle Scholar
  • 54 Darkow T, Vanderplas AM, Lew KH. et al. Treatment patterns and real-world effectiveness of warfarin in nonvalvular atrial fibrillation within a managed care system. Curr Med Res Opin 2005; 21: 1583-1594.
    CrossrefPubMedGoogle Scholar
  • 55 Evans A, Perez I, Yu G, Kalra L. Secondary stroke prevention in atrial fibrillation: lessons from clinical practice. Stroke 2000; 31: 2106-2111.
    CrossrefPubMedGoogle Scholar
  • 56 Friberg L, Hammar N, Rosenqvist M. Stroke in paroxysmal atrial fibrillation: report from the Stockholm Cohort of Atrial Fibrillation. Eur Heart J 2009; 31: 967-975.
    PubMedGoogle Scholar
  • 57 Go AS, Hylek EM, Chang Y. et al. Anticoagulation therapy for stroke prevention in atrial fibrillation: how well do randomized trials translate into clinical practice?. J Am Med Assoc 2003; 290: 2685-2692.
    CrossrefPubMedGoogle Scholar
  • 58 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
  • 59 Gottlieb LK, Salem-Schatz S. Anticoagulation in atrial fibrillation. Does efficacy in clinical trials translate into effectiveness in practice? Arch Intern Med 1994; 154: 1945-1953.
    PubMedGoogle Scholar
  • 60 Jackson SL, Peterson GM, Vial JH. et al. Outcomes in the management of atrial fibrillation: clinical trial results can apply in practice. Intern Med J 2001; 31: 329-336.
    CrossrefPubMedGoogle Scholar
  • 61 Komatsu T, Tachibana H, Sato Y. et al. Relationship between CHADS2 score and ischaemic stroke during rhythm control therapy for paroxysmal atrial fibrillation. Int Heart J 2010; 51: 24-29.
    CrossrefPubMedGoogle Scholar
  • 62 Lee BH, Park JS, Park JH. et al. The effect and safety of the antithrombotic therapies in patients with atrial fibrillation and CHADS score 1. J Cardiovasc Electrophysiol 2010; 21: 501-507.
    CrossrefPubMedGoogle Scholar
  • 63 Nichol MB, Knight TK, Dow T. et al. Quality of anticoagulation monitoring in nonvalvular atrial fibrillation patients: comparison of anticoagulation clinic versus usual care. Ann Pharmacother 2008; 42: 62-70.
    CrossrefPubMedGoogle Scholar
  • 64 Ono A, Fujita T. Low-intensity anticoagulation for stroke prevention in elderly patients with atrial fibrillation: efficacy and safety in actual clinical practice. J Clin Neurosci 2005; 12: 891-894.
    CrossrefPubMedGoogle Scholar
  • 65 Ruiz OM, Romo E, Mesa D. et al. Predicting embolic events in patients with nonvalvular atrial fibrillation: evaluation of the CHADS2 score in a Mediterranean population. Rev Esp Cardiol 2008; 61: 29-35.
    CrossrefPubMedGoogle Scholar
  • 66 Schauer DP, Moomaw CJ, Wess M. et al. Psychosocial risk factors for adverse outcomes in patients with nonvalvular atrial fibrillation receiving warfarin. J Gen Intern Med 2005; 20: 1114-1119.
    CrossrefPubMedGoogle Scholar
  • 67 Shen AY, Yao JF, Brar SS. et al. Racial/Ethnic differences in ischaemic stroke rates and the efficacy of warfarin among patients with atrial fibrillation. Stroke 2008; 39: 2736-2743.
    CrossrefPubMedGoogle Scholar
  • 68 Tentschert S, Parigger S, Dorda V. et al. Recurrent vascular events in patients with ischaemic stroke/TIA and atrial fibrillation in relation to secondary prevention at hospital discharge. Wien Klin Wochenschr 2004; 116: 834-838.
    CrossrefPubMedGoogle Scholar
  • 69 Walker AM, Bennett D. Epidemiology and outcomes in patients with atrial fibrillation in the United States. Heart Rhythm 2008; 5: 1365-1372.
    CrossrefPubMedGoogle Scholar
  • 70 Wess ML, Schauer DP, Johnston JA. et al. Application of a decision support tool for anticoagulation in patients with non-valvular atrial fibrillation. J Gen Intern Med 2008; 23: 411-417.
    CrossrefPubMedGoogle Scholar
  • 71 Yousef ZR, Tandy SC, Tudor V. et al. Warfarin for non-rheumatic atrial fibrillation: five year experience in a district general hospital. Heart 2004; 90: 1259-1262.
    CrossrefPubMedGoogle Scholar
  • 72 Aspinall SL, DeSanzo BE, Trilli LE. et al. Bleeding Risk Index in an anticoagulation clinic. Assessment by indication and implications for care. J Gen Intern Med 2005; 20: 1008-1013.
    CrossrefPubMedGoogle Scholar
  • 73 Currie CJ, McEwan P, Emmas C. et al. Anticoagulation in patients with non-valvular atrial fibrillation: an evaluation of stability and early factors that predict longer-term stability on warfarin in a large UK population. Curr Med Res Opin 2005; 21: 1905-1913.
    CrossrefPubMedGoogle Scholar
  • 74 Fang MC, Go AS, Hylek EM. et al. Age and the risk of warfarin-associated hemorrhage: the anticoagulation and risk factors in atrial fibrillation study. J Am Geriatr Soc 2006; 54: 1231-1236.
    CrossrefPubMedGoogle Scholar
  • 75 Kim JH, Song YB, Shin DH. et al. How well does the target INR level maintain in warfarin-treated patients with non-valvular atrial fibrillation?. Yonsei Med J 2009; 50: 83-88.
    CrossrefPubMedGoogle Scholar
  • 76 Neree C. Quality of oral anticoagulation in patients with atrial fibrillation: a cross-sectional study in general practice. Eur J Gen Pract 2006; 12: 163-168.
    CrossrefPubMedGoogle Scholar
  • 77 Pisters R, Lane DA, Nieuwlaat R. et al. A novel user-friendly score (HAS-BLED) to assess one-year risk of major bleeding in atrial fibrillation patients: The Euro Heart Survey. Chest 2010; 138: 1093-1100.
    CrossrefPubMedGoogle Scholar
  • 78 Poli D, Antonucci E, Lombardi A. et al. Low incidence of hemorrhagic complications of oral anticoagulant therapy in patients with atrial fibrillation in the daily practice of an anticoagulation clinic. Ital Heart J 2003; 4: 44-47.
    PubMedGoogle Scholar
  • 79 Poli D, Antonucci E, Lombardi A. et al. Management of oral anticoagulant therapy in the real practice of an anticoagulation clinic: focus on atrial fibrillation. Blood Coagul Fibrinolysis 2005; 16: 491-494.
    PubMedGoogle Scholar
  • 80 Poli D, Antonucci E, Cecchi E. et al. Culprit factors for the failure of well-conducted warfarin therapy to prevent ischaemic events in patients with atrial fibrillation: the role of homocysteine. Stroke 2005; 36: 2159-2163.
    CrossrefPubMedGoogle Scholar
  • 81 Rose AJ, Ozonoff A, Henault LE. et al. Anticoagulation for valvular heart disease in community-based practice. Thromb Haemost 2010; 103: 329-337.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 82 Ruiz Ortiz M, Romo E, Mesa D. et al. Oral anticoagulation in nonvalvular atrial fibrillation in clinical practice: impact of CHADS(2) score on outcome. Cardiology 2010; 115: 200-204.
    CrossrefPubMedGoogle Scholar
  • 83 Shireman TI, Howard PA, Kresowik TF. et al. Combined anticoagulant-antiplatelet use and major bleeding events in elderly atrial fibrillation patients. Stroke 2004; 35: 2362-2367.
    CrossrefPubMedGoogle Scholar
  • 84 Suzuki S, Yamashita T, Kato T. et al. Incidence of major bleeding complication of warfarin therapy in Japanese patients with atrial fibrillation. Circ J 2007; 71: 761-765.
    CrossrefPubMedGoogle Scholar
  • 85 Trullas-Vila JC, Bisbe-Company J, Freitas-Ramirez A. et al. Ten-year experience with acenocoumarol treatment in an ambulatory cohort of Spanish patients. J Thromb Thrombolysis 2009; 28: 436-443.
    CrossrefPubMedGoogle Scholar