Clinical research study| Volume 123, ISSUE 7, P638-645.e4, July 2010

Underuse of Oral Anticoagulants in Atrial Fibrillation: A Systematic Review



      Atrial fibrillation is associated with substantial mortality and morbidity from stroke and thromboembolism. Despite an efficacious oral anticoagulation therapy (warfarin), atrial fibrillation patients at high risk for stroke are often under-treated. This systematic review compares current treatment practices for stroke prevention in atrial fibrillation with published guidelines.


      Literature searches (1997-2008) identified 98 studies concerning current treatment practices for stroke prevention in atrial fibrillation. The percentage of patients eligible for oral anticoagulation due to elevated stroke risk was compared with the percentage treated. Under-treatment was defined as treatment of <70% of high-risk patients.


      Of 54 studies that reported stroke risk levels and the percentage of patients treated, most showed underuse of oral anticoagulants for high-risk patients. From 29 studies of patients with prior stroke/transient ischemic attack who should all receive oral anticoagulation according to published guidelines, 25 studies reported under-treatment, with 21 of 29 studies reporting oral anticoagulation treatment levels below 60% (range 19%-81.3%). Subjects with a CHADS2 (congestive heart failure, hypertension, age >75 years, diabetes mellitus, and prior stroke or transient ischemic attack) score ≥2 also were suboptimally treated, with 7 of 9 studies reporting treatment levels below 70% (range 39%-92.3%). Studies (21 of 54) using other stroke risk stratification schemes differ in the criteria they use to designate patients as “high risk,” such that direct comparison is not possible.


      This systematic review demonstrates the underuse of oral anticoagulation therapy for real-world atrial fibrillation patients with an elevated risk of stroke, highlighting the need for improved therapies for stroke prevention in atrial fibrillation.


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        • Go A.S.
        • Hylek E.M.
        • Phillips K.A.
        • 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.
        JAMA. 2001; 285: 2370-2375
        • Murphy N.F.
        • Simpson C.R.
        • Jhund P.S.
        • et al.
        A national survey of the prevalence, incidence, primary care burden and treatment of atrial fibrillation in Scotland.
        Heart. 2007; 93: 606-612
        • Miyasaka Y.
        • Barnes M.E.
        • Gersh B.J.
        • 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
        • Watanabe H.
        • Tanabe N.
        • Watanabe T.
        • et al.
        Metabolic syndrome and risk of development of atrial fibrillation: the Niigata preventive medicine study.
        Circulation. 2008; 117: 1255-1260
        • Heeringa J.
        • van der Kuip D.A.
        • Hofman A.
        • et al.
        Prevalence, incidence and lifetime risk of atrial fibrillation: the Rotterdam study.
        Eur Heart J. 2006; 27: 949-953
        • 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 [French].
        Bull Acad Natl Med. 2007; 191: 791-803
        • 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
        • Fang M.C.
        • Go A.S.
        • 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
        • The Stroke Risk in Atrial Fibrillation Working Group
        Independent predictors of stroke in patients with atrial fibrillation: a systematic review.
        Neurology. 2007; 69: 546-554
        • Hughes M.
        • Lip G.Y.
        Stroke and thromboembolism in atrial fibrillation: a systematic review of stroke risk factors, risk stratification schema and cost effectiveness data.
        Thromb Haemost. 2008; 99: 295-304
        • Fuster V.
        • Ryden L.E.
        • Cannom D.S.
        • 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
        • Singer D.E.
        • Albers G.W.
        • Dalen J.E.
        • et al.
        Antithrombotic therapy in atrial fibrillation: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy.
        Chest. 2004; 126: 429S-456S
        • Goldstein L.B.
        • Adams R.
        • Alberts M.J.
        • et al.
        Primary prevention of ischemic 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
        • National Institute for Health and Clinical Excellence
        NICE Clinical Guideline 36—Atrial Fibrillation: The Management of Atrial Fibrillation.
        National Institute for Health and Clinical Excellence, London2006
        • Hankey G.J.
        Non-valvular atrial fibrillation and stroke prevention.
        Med J Aust. 2001; 174: 234-239
        • Stroke Risk in Atrial Fibrillation Working Group
        Comparison of 12 risk stratification schemes to predict stroke in patients with nonvalvular atrial fibrillation.
        Stroke. 2008; : 1-11
        • Gage B.F.
        • Waterman A.D.
        • Shannon W.
        • et al.
        Validation of clinical classification schemes for predicting stroke: results from the National Registry of Atrial Fibrillation.
        JAMA. 2001; 285: 2864-2870
        • Baruch L.
        • Gage B.F.
        • Horrow J.
        • et al.
        Can patients at elevated risk of stroke treated with anticoagulants be further risk stratified?.
        Stroke. 2007; 38: 2459-2463
        • Wolf P.A.
        • Abbott R.D.
        • Kannel W.B.
        Atrial fibrillation as an independent risk factor for stroke: the Framingham Study.
        Stroke. 1991; 22: 983-988
        • Hart R.G.
        • Pearce L.A.
        • McBride R.
        • et al.
        Factors associated with ischemic stroke during aspirin therapy in atrial fibrillation: analysis of 2012 participants in the SPAF I-III clinical trials.
        Stroke. 1999; 30: 1223-1229
        • Wang T.J.
        • Massaro J.M.
        • Levy D.
        • et al.
        A risk score for predicting stroke or death in individuals with new-onset atrial fibrillation in the community: the Framingham Heart Study.
        JAMA. 2003; 290: 1049-1056
        • Nieuwlaat R.
        • Capucci A.
        • Lip G.Y.
        • 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
        • Fuster V.
        • Ryden L.E.
        • Asinger R.W.
        • et al.
        ACC/AHA/ESC Guidelines for the Management of Patients With Atrial Fibrillation: Executive Summary 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 and Policy Conferences (Committee to Develop Guidelines for the Management of Patients With Atrial Fibrillation) developed in collaboration with the North American Society of Pacing and Electrophysiology.
        Circulation. 2001; 104: 2118-2150
        • Dewilde S.
        • Carey I.M.
        • Emmas C.
        • et al.
        Trends in the prevalence of diagnosed atrial fibrillation, its treatment with anticoagulation and predictors of such treatment in UK primary care.
        Heart. 2006; 92: 1064-1070
        • Frykman V.
        • Beerman B.
        • Ryden L.
        • et al.
        Management of atrial fibrillation: discrepancy between guideline recommendations and actual practice exposes patients to risk for complications.
        Eur Heart J. 2001; 22: 1954-1959
        • Kalra L.
        • Yu G.
        • Perez I.
        • et al.
        Prospective cohort study to determine if trial efficacy of anticoagulation for stroke prevention in atrial fibrillation translates into clinical effectiveness.
        BMJ. 2000; 320: 1236-1239
        • Bravata D.M.
        • Rosenbeck K.
        • Kancir S.
        • Brass L.M.
        The use of warfarin in veterans with atrial fibrillation.
        BMC Cardiovasc Disord. 2004; 4: 18
        • Go A.S.
        • Hylek E.M.
        • Borowsky L.H.
        • 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
        • Gandolfo C.
        • Balestrino M.
        • Burrone A.
        • et al.
        Stroke due to atrial fibrillation and the attitude to prescribing anticoagulant prevention in Italy: a prospective study of a consecutive stroke population admitted to a comprehensive stroke unit.
        J Neurol. 2008; 255: 796-802
        • Humphries K.H.
        • Jackevicius C.
        • Gong Y.
        • et al.
        Population rates of hospitalization for atrial fibrillation/flutter in Canada.
        Can J Cardiol. 2004; 20: 869-876
        • Rowan S.B.
        • Bailey D.N.
        • Bublitz C.E.
        • et al.
        Trends in anticoagulation for atrial fibrillation in the U.S.: an analysis of the national ambulatory medical care survey database.
        J Am Coll Cardiol. 2007; 49: 1561-1565
        • Evans A.
        • Kalra L.
        Are the results of randomized controlled trials on anticoagulation in patients with atrial fibrillation generalizable to clinical practice?.
        Arch Intern Med. 2001; 161: 1443-1447
        • Leckey R.
        • Aguilar E.G.
        • Phillips S.J.
        Atrial fibrillation and the use of warfarin in patients admitted to an acute stroke unit.
        Can J Cardiol. 2000; 16: 481-485
        • 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
        • Meiltz A.
        • Zimmermann M.
        • Urban P.
        • Bloch A.
        • Association of Cardiologists of the Canton of Geneva
        Atrial fibrillation management by practice cardiologists: a prospective survey on the adherence to guidelines in the real world.
        Europace. 2008; 10: 674-680
        • Suzuki S.
        • Yamashita T.
        • Ohtsuka T.
        • et al.
        Prevalence and prognosis of patients with atrial fibrillation in Japan: a prospective cohort of Shinken Database 2004.
        Circ J. 2008; 72: 914-920
        • Srivastava A.
        • Hudson M.
        • Hamoud I.
        • et al.
        Examining warfarin underutilization rates in patients with atrial fibrillation: detailed chart review essential to capture contraindications to warfarin therapy.
        Thromb J. 2008; 6: 6
        • Partington S.L.
        • Abid S.
        • Teo K.
        • et al.
        Pre-admission warfarin use in patients with acute ischemic stroke and atrial fibrillation: the appropriate use and barriers to oral anticoagulant therapy.
        Thromb Res. 2007; 120: 663-669
        • Boulanger L.
        • Kim J.
        • Friedman M.
        • et al.
        Patterns of use of antithrombotic therapy and quality of anticoagulation among patients with non-valvular atrial fibrillation in clinical practice.
        Int J Clin Pract. 2006; 60: 258-264
        • Birman-Deych E.
        • Radford M.J.
        • Nilasena D.S.
        • et al.
        Use and effectiveness of warfarin in Medicare beneficiaries with atrial fibrillation.
        Stroke. 2006; 37: 1070-1074
        • Inoue H.
        • Nozawa T.
        • Hirai T.
        • et al.
        Accumulation of risk factors increases risk of thromboembolic events in patients with nonvalvular atrial fibrillation.
        Circ J. 2006; 70: 651-656
        • Brophy M.T.
        • Snyder K.E.
        • Gaehde S.
        • et al.
        Anticoagulant use for atrial fibrillation in the elderly.
        J Am Geriatr Soc. 2004; 52: 1151-1156
        • Filippi A.
        • Bettoncelli G.
        • Zaninelli A.
        Detected atrial fibrillation in north Italy: rates, calculated stroke risk and proportion of patients receiving thrombo-prophylaxis.
        Fam Pract. 2000; 17: 337-339
        • Bo S.
        • Valpreda S.
        • Scaglione L.
        • et al.
        Implementing hospital guidelines improves warfarin use in non-valvular atrial fibrillation: a before-after study.
        BMC Public Health. 2007; 7: 203
        • Wolf P.A.
        • Abbott R.D.
        • Kannel W.B.
        Atrial fibrillation: a major contributor to stroke in the elderly.
        Arch Intern Med. 1987; 147: 1561-1564
        • Glazer N.L.
        • Dublin S.
        • Smith N.L.
        • et al.
        Newly detected atrial fibrillation and compliance with antithrombotic guidelines.
        Arch Intern Med. 2007; 167: 246-252
        • Reynolds M.R.
        • Shah J.
        • Essebag V.
        • et al.
        Patterns and predictors of warfarin use in patients with new-onset atrial fibrillation from the FRACTAL Registry.
        Am J Cardiol. 2006; 97: 538-543
        • 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
        • Anderson N.
        • Fuller R.
        • Dudley N.
        ‘Rules of thumb’ or reflective practice?.
        QJM. 2007; 100: 263-269
        • Hylek E.M.
        • Go A.S.
        • 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
        • Hylek E.M.
        • Singer D.E.
        Risk factors for intracranial hemorrhage in outpatients taking warfarin.
        Ann Intern Med. 1994; 120: 897-902
        • Darkow T.
        • Vanderplas A.M.
        • Lew K.H.
        • 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
        • Hughes M.
        • Lip G.Y.
        Risk factors for anticoagulation-related bleeding complications in patients with atrial fibrillation: a systematic review.
        QJM. 2007; 100: 599-607
        • Go A.S.
        Efficacy of anticoagulation for stroke prevention and risk stratification in atrial fibrillation: translating trials into clinical practice.
        Am J Manag Care. 2004; 10: S58-S65
        • McNamara R.L.
        • Tamariz L.J.
        • Segal J.B.
        • et al.
        Management of atrial fibrillation: review of the evidence for the role of pharmacologic therapy, electrical cardioversion, and echocardiography.
        Ann Intern Med. 2003; 139: 1018-1033
        • van Walraven C.
        • Hart R.G.
        • Connolly S.
        • et al.
        Effect of age on stroke prevention therapy in patients with atrial fibrillation.
        Stroke. 2009; 40: 1410-1416
        • Hansen M.L.
        • Gadsboll N.
        • Gislason G.H.
        • et al.
        Atrial fibrillation pharmacotherapy after hospital discharge between 1995 and 2004: a shift towards beta-blockers.
        Europace. 2008; 10: 395-402
        • Leoo T.
        • Lindgren A.
        • Petersson J.
        • et al.
        Risk factors and treatment at recurrent stroke onset: results from the Recurrent Stroke Quality and Epidemiology (RESQUE) Study.
        Cerebrovasc Dis. 2008; 25: 254-260
        • Fornari L.S.
        • Calderaro D.
        • Nassar I.B.
        • et al.
        Misuse of antithrombotic therapy in atrial fibrillation patients: frequent, pervasive and persistent.
        J Thromb Thrombolysis. 2007; 23: 65-71
        • Andersen K.K.
        • Olsen T.S.
        Reduced poststroke mortality in patients with stroke and atrial fibrillation treated with anticoagulants: results from a Danish quality-control registry of 22,179 patients with ischemic stroke.
        Stroke. 2007; 38: 259-263
        • Burgess C.
        • Ingham T.
        • Woodbridge M.
        • et al.
        The use of antithrombotics in patients presenting with stroke and atrial fibrillation.
        Ther Clin Risk Manag. 2007; 3: 491-498
        • Deplanque D.
        • Leys D.
        • Parnetti L.
        • et al.
        Secondary prevention of stroke in patients with atrial fibrillation: factors influencing the prescription of oral anticoagulation at discharge.
        Cerebrovasc Dis. 2006; 21: 372-379
        • 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
        • Touze E.
        • Cambou J.P.
        • Ferrieres J.
        • et al.
        Antithrombotic management after an ischemic stroke in French primary care practice: results from three pooled cross-sectional studies.
        Cerebrovasc Dis. 2005; 20: 78-84
        • de Lusignan S.
        • van Vlymen J.
        • Hague N.
        • et al.
        Preventing stroke in people with atrial fibrillation: a cross-sectional study.
        J Public Health (Oxf). 2005; 27: 85-92
        • Bordin P.
        • Mazzone C.
        • Pandullo C.
        • et al.
        Morbidity and mortality in 229 elderly patients with nonrheumatic atrial fibrillation.
        Ital Heart J. 2003; 4: 537-543
        • Go A.S.
        • Hylek E.M.
        • Chang Y.
        • et al.
        Anticoagulation therapy for stroke prevention in atrial fibrillation: how well do randomized trials translate into clinical practice?.
        JAMA. 2003; 290: 2685-2692
        • Evans A.
        • Perez I.
        • Yu G.
        • et al.
        Should stroke subtype influence anticoagulation decisions to prevent recurrence in stroke patients with atrial fibrillation?.
        Stroke. 2001; 32: 2828-2832
        • Howard P.A.
        • Ellerbeck E.F.
        • Engelman K.K.
        • et al.
        Warfarin for stroke prevention in octogenarians with atrial fibrillation.
        Am J Geriatr Cardiol. 2001; 10: 139-144
        • Cohen N.
        • Almoznino-Sarafian D.
        • Alon I.
        • et al.
        Warfarin for stroke prevention still underused in atrial fibrillation: patterns of omission.
        Stroke. 2000; 31: 1217-1222
        • Tomita F.
        • Kohya T.
        • Sakurai M.
        • et al.
        Prevalence and clinical characteristics of patients with atrial fibrillation: analysis of 20,000 cases in Japan.
        Jpn Circ J. 2000; 64: 653-658
        • Gage B.F.
        • Boechler M.
        • Doggette A.L.
        • et al.
        Adverse outcomes and predictors of underuse of antithrombotic therapy in medicare beneficiaries with chronic atrial fibrillation.
        Stroke. 2000; 31: 822-827
        • Caro J.J.
        • Flegel K.M.
        • Orejuela M.E.
        • et al.
        Anticoagulant prophylaxis against stroke in atrial fibrillation: effectiveness in actual practice.
        CMAJ. 1999; 161: 493-497
        • Deplanque D.
        • Corea F.
        • Arquizan C.
        • et al.
        Stroke and atrial fibrillation: is stroke prevention treatment appropriate beforehand?.
        Heart. 1999; 82: 563-569
        • White R.H.
        • McBurnie M.A.
        • Manolio T.
        • et al.
        Oral anticoagulation in patients with atrial fibrillation: adherence with guidelines in an elderly cohort.
        Am J Med. 1999; 106: 165-171
        • Brass L.M.
        • Krumholz H.M.
        • Scinto J.D.
        • et al.
        Warfarin use following ischemic stroke among Medicare patients with atrial fibrillation.
        Arch Intern Med. 1998; 158: 2093-2100
        • Brass L.M.
        • Krumholz H.M.
        • Scinto J.M.
        • et al.
        Warfarin use among patients with atrial fibrillation.
        Stroke. 1997; 28: 2382-2389
        • Gurwitz J.H.
        • Monette J.
        • Rochon P.A.
        • et al.
        Atrial fibrillation and stroke prevention with warfarin in the long-term care setting.
        Arch Intern Med. 1997; 157: 978-984

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