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‘Real-World’ Antithrombotic Treatment in Atrial Fibrillation: The EORP-AF Pilot Survey

Published:January 30, 2014DOI:https://doi.org/10.1016/j.amjmed.2013.12.022

      Abstract

      Background

      Current guidelines strongly recommend that oral anticoagulation should be offered to patients with atrial fibrillation and ≥1 stroke risk factors. The guidelines also recommend that oral anticoagulation still should be used in the presence of stroke risk factors irrespective of rate or rhythm control.

      Methods

      In an analysis from the dataset of the EURObservational Research Programme on Atrial Fibrillation Pilot Survey (n = 3119), we examined antithrombotic therapy prescribing, with particular focus on the risk factors determining oral anticoagulation or antiplatelet therapy use.

      Results

      When oral anticoagulation was used among admitted patients in whom no pharmacologic cardioversion, electrical cardioversion, or catheter ablation was performed or planned, vitamin K antagonist therapy was prescribed in the majority (72.2%), whereas novel oral anticoagulants were used in the minority (7.7%). There was no significant difference in bleeding risk factors among the patients treated with the different types of antithrombotic therapies, except for those with chronic kidney disease, in whom oral anticoagulation was less commonly used (P = .0318). Antiplatelet therapy was more commonly used in patients with a high Hypertension, Abnormal renal/liver function, Stroke, Bleeding history or predisposition, Labile international normalized ratio, Elderly (>65 years), Drugs/alcohol concomitantly score (≥2) (P < .0001). More oral anticoagulation use was associated with female gender (P = .0245). Less novel oral anticoagulant use was associated with valvular heart disease (P < .0001), chronic heart failure (P = .0010), coronary artery disease (P < .0001), and peripheral artery disease (P = .0092). Coronary artery disease was the strongest reason for combination therapy with oral anticoagulation plus antiplatelet drug (odds ratio, 8.54; P < .0001). When the Congestive heart failure, Hypertension, Age ≥75 [Doubled], Diabetes, Stroke [Doubled]-Vascular disease, Age 65-74, and Sex category [female] score was used, 95.6% of patients with a score ≥1 received antithrombotic therapy, with 80.5% of patients with a score ≥1 receiving oral anticoagulation. Of note, 83.7% of those with a score ≥2 received antithrombotic therapy. Of the latter, 70.9% of those with a score ≥2 received oral anticoagulation, vitamin K antagonists were used in 64.1%, and novel oral anticoagulants were used in 6.9%.

      Conclusions

      The EURObservational Research Programme on Atrial Fibrillation Pilot Survey provides contemporary data on oral anticoagulation prescribing by European cardiologists for atrial fibrillation. Although the uptake of oral anticoagulation (mostly vitamin K antagonist therapy) has improved since the Euro Heart Survey a decade ago, antiplatelet therapy is still commonly prescribed, with or without oral anticoagulation, whereas elderly patients are commonly undertreated with oral anticoagulation.

      Keywords

      • The EURObservational Research Programme on Atrial Fibrillation (EORP-AF) Pilot Survey provides contemporary data on oral anticoagulation prescribing by European cardiologists.
      • When oral anticoagulation was used, vitamin K antagonists were prescribed in the majority of patients (72.2%). Novel oral anticoagulants were used in the minority (7.7%) of patients. In addition, 80.5% of patients with a Congestive heart failure, Hypertension, Age ≥75 [Doubled], Diabetes, Stroke [Doubled]-Vascular disease, Age 65-74, and Sex category [female] (CHA2DS2-VASc) score ≥1 received oral anticoagulation.
      • Antiplatelet therapy is still overprescribed, with or without oral anticoagulation, whereas elderly patients are commonly undertreated with oral anticoagulation.
      Stroke prevention is central to the management of atrial fibrillation.
      • Banerjee A.
      • Marin F.
      • Lip G.Y.
      The improved but unfinished business of stroke risk stratification in atrial fibrillation.
      This common arrhythmia is associated with a high risk of stroke and thromboembolism, and when strokes occur in association with atrial fibrillation, there is greater mortality and morbidity with more disability, longer hospital stays, and a lower rate of discharge to the patient's home.
      • Banerjee A.
      • Marin F.
      • Lip G.Y.
      The improved but unfinished business of stroke risk stratification in atrial fibrillation.
      In the Euro Heart Survey report from 2006, Nieuwlaat et al
      • 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.
      concluded that antithrombotic therapy in atrial fibrillation was hardly tailored to the patient's stroke risk profile and suggested that factors other than well-known stroke risk factors were significantly involved in antithrombotic management decisions. There was a call that guideline writers and physician educators should focus on providing one uniform and easy to use stroke risk stratification scheme. Since the Euro Heart Survey, the European Society of Cardiology (ESC) has produced new guidelines
      • Camm A.J.
      • Lip G.Y.
      • De Caterina R.
      • et al.
      2012 focused update of the ESC Guidelines for the management of atrial fibrillation: an update of the 2010 ESC Guidelines for the management of atrial fibrillation–developed with the special contribution of the European Heart Rhythm Association.
      and introduced use of the Congestive heart failure, Hypertension, Age ≥75 [Doubled], Diabetes, Stroke [Doubled]-Vascular disease, Age 65-74, and Sex category [female]
      • Lip G.Y.
      • Nieuwlaat R.
      • Pisters R.
      • Lane D.A.
      • Crijns H.J.
      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.
      (CHA2DS2-VASc) and Hypertension, Abnormal renal/liver function, Stroke, Bleeding history or predisposition, Labile international normalized ratio, Elderly (>65 years), Drugs/alcohol concomitantly (HAS-BLED)
      • Pisters R.
      • Lane D.A.
      • Nieuwlaat R.
      • de Vos C.B.
      • Crijns H.J.
      • Lip G.Y.
      A novel user-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in patients with atrial fibrillation: the Euro Heart Survey.
      scores for stroke and bleeding risk stratification, respectively. The availability of novel oral anticoagulants also has changed the landscape for stroke prevention, given their efficacy, safety, and relative convenience.
      • Kornej J.
      • Potpara T.
      • Lip G.Y.
      Anticoagulation management in non-valvular atrial fibrillation: current and future directions.
      Of importance, the 2012 focused update of the ESC guidelines strongly recommended a clinical practice shift, so that the initial decision step is the identification of “truly low-risk” patients with atrial fibrillation who do not need any antithrombotic therapy.
      • Camm A.J.
      • Lip G.Y.
      • De Caterina R.
      • et al.
      2012 focused update of the ESC Guidelines for the management of atrial fibrillation: an update of the 2010 ESC Guidelines for the management of atrial fibrillation–developed with the special contribution of the European Heart Rhythm Association.
      Subsequent to this step, effective stroke prevention (essentially oral anticoagulation) can be offered to patients with ≥1 stroke risk factors. More recently, similar recommendations from the Asia Pacific Heart Rhythm Society were published.
      • Ogawa S.
      • Aonuma K.
      • Tse H.F.
      • et al.
      The APHRS's 2013 statement on antithrombotic therapy of patients with nonvalvular atrial fibrillation.
      Also, the ESC guidelines recommended that oral anticoagulation should still be used in the presence of stroke risk factors irrespective of rate or rhythm control and whether the latter was successful.
      • Camm A.J.
      • Lip G.Y.
      • De Caterina R.
      • et al.
      2012 focused update of the ESC Guidelines for the management of atrial fibrillation: an update of the 2010 ESC Guidelines for the management of atrial fibrillation–developed with the special contribution of the European Heart Rhythm Association.
      American and Canadian guidelines are broadly similar, recommending oral anticoagulation for patients with stroke risk factors, irrespective of whether a rhythm-control strategy was successful.
      • You J.J.
      • Singer D.E.
      • Howard P.A.
      • et al.
      Antithrombotic therapy for atrial fibrillation: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-based Clinical Practice Guidelines.
      • Skanes A.
      • Healey J.
      • Cairns J.
      • et al.
      Focused 2012 update of the Canadian Cardiovascular Society Atrial Fibrillation Guidelines: recommendations for stroke prevention and rate/rhythm control.
      • Fuster V.
      • Ryden L.E.
      • Cannom D.S.
      • et al.
      2011 ACCF/AHA/HRS focused updates incorporated into the ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation: a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines developed in partnership with the European Society of Cardiology and in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society.
      In this analysis from the baseline dataset of the EURObservational Research Programme on Atrial Fibrillation (EORP-AF) Pilot Survey, we examined antithrombotic therapy prescribing, with particular focus on the risk factors determining oral anticoagulation or antiplatelet therapy use. Furthermore, we assessed the uptake of oral anticoagulation use among patients undergoing rhythm control (cardioversion or ablation).

      Materials and Methods

      The full baseline features and results from the EORP-AF Pilot Survey have been published.
      • Lip G.Y.
      • Laroche C.
      • Dan G.A.
      • et al.
      A prospective survey in European Society of Cardiology member countries of atrial fibrillation management: baseline results of EURObservational Research Programme Atrial Fibrillation (EORP-AF) Pilot General Registry.
      In this ancillary analysis, we focused on the clinical features associated with antithrombotic therapy use. In brief, the registry population comprised consecutive inpatients and outpatients with atrial fibrillation presenting to cardiologists in participating ESC countries. Consecutive patients were screened for eligibility at the time of their presentation to a cardiologist (hospital or medical center). All patients provided written informed consent. Patients with the primary or secondary recorded diagnosis of atrial fibrillation were included.
      Patients were officially enrolled in the EORP-AF only if an electrocardiographic diagnosis (12-lead electrocardiogram, 24-hour Holter, or other electrocardiographic documentation) confirming atrial fibrillation was made. The qualifying episode of atrial fibrillation should have occurred within the last year, and patients did not need to be in atrial fibrillation at the time of enrollment. For the pilot phase, 9 countries formally participated. A minimum of 20 consecutive patients per center were to be enrolled, with a target of 3000 patients. Enrollment in the registry started in February 2012, and the end of enrollment was March 2013.

      Statistical Analyses

      Univariate analysis was applied to both continuous and categoric variables. Continuous variables were reported as mean ± standard deviation or as median and interquartile range. Among-group comparisons were made using a nonparametric test (Kruskal–Wallis test). Categoric variables were reported as percentages. Among-group comparisons were made using a chi-square test or a Fisher exact test if any expected cell count was less than 5.

      Results

      We enrolled 3119 patients from February 2012 to March 2013. Table 1 shows the characteristics versus antithrombotic drug use of patients admitted to the hospital in whom no pharmacologic or electrical cardioversion and catheter ablation were performed or planned. In the whole cohort, when oral anticoagulation was used, vitamin K antagonist therapy was prescribed in the majority (651/902 = 72.2%), whereas novel oral anticoagulants were used in the minority (69/902 = 7.7%). No antithrombotic therapy was used in 2.7% of patients (24/902).
      Table 1Characteristics Versus Antithrombotic Drug Use in Hospitalized Patients with Atrial Fibrillation Where No Pharmacologic Cardioversion, Electrical Cardioversion, or Catheter Ablation Was Performed or Planned
      Whole CohortNone and UnknownOAC AloneAntiplatelet AloneOAC + AntiplateletOther
      Others include OAC + other antithrombotic therapy, antiplatelet + other antithrombotic therapy, OAC + antiplatelet + other antithrombotic therapy and other antithrombotic therapy (fondaparinux, low-molecular weight heparin, unfractionated heparin, other).
      P Value
      No.9022448212719376
      Reason for visit:
       AF (%)31.6058.3334.8530.7122.8026.32
       Acute myocardial infarction (%)8.204.170.8316.5420.7310.53
       Valvular heart disease (%)7.104.176.436.306.7414.47
       Hypertension (%)1.330.001.660.791.041.32<.0001
       Heart failure (%)31.6020.8339.4229.1318.6522.37
       Other coronary artery disease (%)8.870.002.909.4521.2417.11
       Other cardiac (%)8.5412.5011.413.946.222.63
       Other noncardiac reason (%)2.770.002.493.152.595.26
      Demographics:
       Age (y) (mean ± SD)71.16 ± 11.361.46 ± 14.670.16 ± 11.475.27 ± 11.371.62 ± 10.472.53 ± 9.0<.0001
       Age (y) (median, IQR)73.0 (64.0-79.0)64.5 (49.0-72.5)72.0 (64.0-78.0)77.0 (67.0-84.0)72.0 (64.0-79.0)73.0 (66.0-80.0)
       Female gender (%)41.0220.8345.8544.0933.6830.26.0018
      Stroke risk factors:
       Valvular heart disease (%)72.1057.8970.2675.4174.8774.67.3636
       Ischemic thromboembolic complications (%)16.634.1717.1211.0220.4217.33.1051
       Previous TIA (%)4.810.004.404.726.774.05.5425
       Previous stroke (%)7.910.008.546.357.2510.67.4564
       Chronic heart failure (%)63.3763.1668.5254.7656.7762.67.0014
       Hypertension (%)74.0554.1773.2872.2276.6881.58.0830
       Coronary artery disease (%)47.5931.2526.4761.6181.8762.50<.0001
       Peripheral vascular disease (%)15.014.7612.3615.2019.2722.97.0305
       Diabetes mellitus (%)26.6720.8327.2319.6929.2630.26.3075
      Bleeding risk factors:
       Hemorrhagic events (%)9.158.338.777.208.3317.11.1578
       Malignancy (%)4.608.334.174.074.218.11.5269
       Chronic kidney disease (%)21.6233.3319.0930.7119.6923.68.0318
      Type of AF:
       First detected (%)36.4929.1737.7746.8332.9821.92
       Paroxysmal (%)19.0433.3316.0920.6322.3421.92
       Persistent (%)12.5416.6712.027.1413.3021.92.0018
       Long-standing persistent (%)2.390.001.504.762.135.48
       Permanent (%)29.5320.8332.6220.6329.2628.77
      Heart rhythm strategy:
       Rate control only (%)63.5345.8363.6954.3365.8077.63
       Rate and rhythm control (%)24.6133.3323.2430.7127.9811.84.0052
       Rhythm control only (%)5.5412.506.228.662.591.32
       Observation (%)6.328.336.856.303.639.21
      HAS-BLED score:<.0001
       013.6437.517.017.876.7411.84
       134.1520.8342.7421.2626.9423.68
       ≥252.2241.6740.2570.8766.3264.47
      AF = atrial fibrillation; HAS-BLED = Hypertension, Abnormal renal/liver function, Stroke, Bleeding history or predisposition, Labile international normalized ratio, Elderly (>65 years), Drugs/alcohol concomitantly; IQR = interquartile range; LMW = low-molecular-weight; OAC = oral anticoagulation; SD = standard deviation; TIA = transient ischemic attack; UF = unfractionated.
      Others include OAC + other antithrombotic therapy, antiplatelet + other antithrombotic therapy, OAC + antiplatelet + other antithrombotic therapy and other antithrombotic therapy (fondaparinux, low-molecular weight heparin, unfractionated heparin, other).
      Oral anticoagulation was commonly prescribed for permanent atrial fibrillation, usually when heart failure (39.4%) or other cardiac diseases were present. Antiplatelet therapy was commonly prescribed, regardless of whether there was coexistent myocardial infarction or coronary artery disease.
      The mean age of patients prescribed oral anticoagulation was lower than those prescribed antiplatelet therapy alone (P < .0001). There were similar proportions of female patients who were prescribed both oral anticoagulation and antiplatelet therapy (Table 1). Stroke risk factors were not different between various antithrombotic therapy regimens, apart from heart failure (68.5% receiving oral anticoagulation, P = .0014), coronary artery disease (more antiplatelet therapy, P < .0001), and peripheral artery disease (more antiplatelet therapy, P = .0031).
      There was no significant difference in bleeding risk factors between the different types of antithrombotic therapies used, except for chronic kidney disease, for which oral anticoagulation was less commonly used (P = .0318). Antiplatelet therapy was more commonly used in patients with a high HAS-BLED score (≥2) (P < .0001).
      Patients with paroxysmal atrial fibrillation were less likely to receive oral anticoagulation than those with permanent atrial fibrillation, although of the latter, more than 60% received oral anticoagulation alone or in combination with antiplatelet therapy (P = .0018). With regard to management strategy, of those undergoing rate control, most received oral anticoagulation alone or in combination with antiplatelet therapy (P = .0052). Of those receiving oral anticoagulation alone, vitamin K antagonists were used in 90.4% of patients (651/720) and novel oral anticoagulants were used in 9.6% of patients (69/720). Among those receiving combination oral anticoagulation plus antiplatelet therapy, the oral anticoagulant used was a vitamin K antagonist in 92.7% of patients (179/193) and novel oral anticoagulants were used in 7.8% of patients (15/193).

      Factors Associated with Oral Anticoagulation Prescription

      Factors associated with oral anticoagulation prescription are shown in Tables 2 to 5. More oral anticoagulation use was associated with female gender (P = .0245). Less oral anticoagulation use was associated with valvular heart disease, heart failure, coronary or peripheral artery disease (P < .0001), diabetes mellitus (P = .0012), and subtype of atrial fibrillation (P = .0474) (Table 2).
      Table 2Factors Associated with Prescription of Oral Anticoagulation Alone (Vitamin K Antagonists Plus Novel Oral Anticoagulant)
      Odds Ratio95% Confidence LimitsP Value
      Age (%), (reference, <65 y)0.92110.79421.0683.2773
      Female gender (%)1.18131.02161.3661.0245
      Valvular heart disease (%)0.65920.56450.7697<.0001
      Previous TIA/stroke (%)1.25580.97881.6111.0728
      Chronic heart failure (%)0.63430.54770.7345<.0001
      Hypertension (%)0.98150.83931.1479.8153
      Coronary artery disease (%)0.17810.15000.2114<.0001
      Peripheral vascular disease (%)0.55050.43670.6939<.0001
      Diabetes mellitus (%)0.74880.62860.8919.0012
      Type of AF (%), (reference, first detected)0.85490.73210.9983.0474
      Heart rhythm strategy (%), (reference, rhythm control only)1.17790.95161.4581.1323
      AF = atrial fibrillation; TIA = transient ischemic attack.
      More novel oral anticoagulant use was associated with previous transient ischemic attack/stroke (P = .0235) and heart rhythm strategy (P = .0153). Less novel oral anticoagulant use was associated with valvular heart disease (P < .0001), chronic heart failure (P = .0010), coronary artery disease (P < .0001), and peripheral artery disease (P = .0092) (Table 3).
      Table 3Factors Associated with Prescription of Novel Oral Anticoagulants Only (Dabigatran or Rivaroxaban)
      Odds Ratio95% Confidence LimitsP Value
      Age (%), (reference, <65 y)0.79370.61361.0266.0779
      Female gender (%)1.03060.79721.3324.8178
      Valvular heart disease (%)0.58200.44800.7561<.0001
      Previous TIA/stroke (%)1.54391.05752.2540.0235
      Chronic heart failure (%)0.64010.48970.8366.0010
      Hypertension (%)0.91360.69431.2021.5186
      Coronary artery disease (%)0.47860.34480.6645<.0001
      Peripheral vascular disease (%)0.48700.28020.8465.0092
      Diabetes mellitus (%)0.85500.61721.1844.3457
      Type of AF (%), (reference, first detected)1.17200.89481.5352.2487
      Heart rhythm strategy (%), (reference, rhythm control only)1.50861.08002.1074.0153
      AF = atrial fibrillation; TIA = transient ischemic attack.

      Factors Associated with Antiplatelet Drug Prescription

      Factors associated with antiplatelet drug prescription are shown in Table 4. More antiplatelet drug use was associated with female gender (P = .0428), coronary artery disease (P < .0001), and type of atrial fibrillation (P = .0004), with less use in previous stroke/transient ischemic attack (P = .0123) and diabetes (P = .0426) (Table 4).
      Table 4Factors Associated with Prescription of Antiplatelet Drugs Alone
      Odds Ratio95% Confidence LimitsP Value
      Age (%), (reference <65 y)1.06430.85451.3256.5781
      Female gender (%)1.24331.00681.5353.0428
      Valvular heart disease (%)1.05110.83741.3192.6674
      Previous TIA/stroke (%)0.57980.37660.8927.0123
      Chronic heart failure (%)0.86580.69741.0749.1916
      Hypertension (%)0.97520.77491.2271.8301
      Coronary artery disease (%)1.70521.35782.1414<.0001
      Peripheral vascular disease (%)0.89380.63041.2672.5283
      Diabetes mellitus (%)0.75050.56830.9913.0426
      Type of AF (%) (reference = first detected)1.47841.18781.8401.0004
      Heart rhythm strategy (%), (reference = rhythm control only)1.28200.95761.7162.0944
      AF = atrial fibrillation; TIA = transient ischemic attack.

      Factors Associated with Oral Anticoagulation Plus Antiplatelet Drug Prescription

      Factors associated with combination oral anticoagulation plus antiplatelet drug prescriptions are shown in Table 5. More combination therapy with oral anticoagulation plus antiplatelet drug use was associated with age, valvular heart disease, chronic heart failure, hypertension, coronary and peripheral artery disease, and diabetes (all P < .0001). Coronary artery disease was the strongest reason for combination therapy (odds ratio, 8.54; P < .0001) (Table 5). There was less combination therapy with oral anticoagulation plus antiplatelet drug use in female patients (P = .0002), previous stroke/transient ischemic attack (P = .0159), and heart rhythm strategy (P = .0004).
      Table 5Factors Associated with Prescription of Oral Anticoagulation in Combination with Antiplatelet Drugs
      Odds Ratio95% Confidence LimitsP Value
      Age (%), (reference age <65 y)1.58731.30311.9334<.0001
      Female gender (%)0.70000.57980.8450.0002
      Valvular heart disease (%)1.96151.59572.4111<.0001
      Previous TIA/stroke (%)0.57980.37660.8927.0159
      Chronic heart failure (%)2.34151.94112.8246<.0001
      Hypertension (%)1.80981.45532.2508<.0001
      Coronary artery disease (%)8.54866.882310.6182<.0001
      Peripheral vascular disease (%)2.50631.95513.2129<.0001
      Diabetes mellitus (%)1.82281.48552.2368<.0001
      Type of AF (%) (reference = first detected)0.85470.69931.0447.1251
      Heart rhythm strategy (%) (reference = rhythm control only)0.57890.42530.7879.0004
      AF = atrial fibrillation; TIA = transient ischemic attack.

      Risk Factors for Stroke

      In the whole cohort, the most common risk factors for stroke were heart failure (47.5%) and hypertension (29.3%). Among the anticoagulated cohort, the most common stroke risk factor was hypertension (70.5%) (Table 6).
      Table 6Prevalence of Risk Factors for Stroke in Patients According to European Society of Cardiology Guidelines
      Whole CohortOAC Alone
      N%N%
      Heart failure (%)141147.4873942.74
      Hypertension (%)90929.29126270.54
      Age (%):
       <65 y103033.0261334.04
       65-74 y103833.2863135.04
       ≥75 y105133.7055730.93
      Diabetes mellitus (%)63820.5733318.56
      Previous TIA (%)1264.09814.53
      Previous stroke (%)1956.301206.68
      Ischemic thromboembolic complications (%)40513.0925013.94
      Peripheral vascular disease (%)32811.031438.47
      Myocardial infarction (%)43916.331137.30
      Female (%)126040.4075842.09
      OAC = oral anticoagulation; TIA = transient ischemic attack.

      Antithrombotic Therapy Use Based on CHADS2 and CHA2DS2-VASc Scores

      On the basis of the Congestive heart failure, Hypertension, Age ≥75, Diabetes, Stroke [Doubled] (CHADS2) score, 89.3% of those with a score ≥1 received antithrombotic therapy; of these, 75.7% (2243/2964) of those with a score ≥1 received oral anticoagulation: Vitamin K antagonists were used in 68.1% of patients (2019/2964), and novel oral anticoagulants were used in 7.7% of patients (228/2964).
      When the CHA2DS2-VASc score was used, 95.6% with a score ≥1 received antithrombotic therapy, with 80.5% (2386/2964) with a score ≥1 receiving oral anticoagulation. Of note, 83.7% of those with a score ≥2 received anti-thrombotic therapy; of the latter, 70.9% (2101/2964) of those with a score ≥2 received oral anticoagulation. Of the latter anticoagulated patients with a CHA2DS2-VASc score ≥2, vitamin K antagonists were used in 64.1% (1900/2964) and novel oral anticoagulants were used in 6.9% (204/2964).

      Antithrombotic Therapy Use Based on Rhythm Control

      Pharmacologic and electrical cardioversion were planned or performed in 763 and 703 subjects, respectively, whereas catheter ablation was performed or planned in 231 subjects. The clinical characteristics of these patients are summarized in Supplementary Table 1.
      For patients in whom pharmacologic cardioversion was performed or planned (n = 763), oral anticoagulation was used in the majority (at least 66.6% at discharge in those in whom pharmacologic cardioversion was performed, or at least 92.3% when planned). No antiplatelet therapy was used when oral anticoagulation was planned (Table 7, Figure 1). In patients undergoing pharmacologic cardioversion who received oral anticoagulation, vitamin K antagonist therapy was prescribed in the majority (92.1%, 477/518 at discharge), whereas novel oral anticoagulants were used in the minority (8.1%, 42/518 at discharge). (One patient received both vitamin K antagonist and novel oral anticoagulants, so n = 477 + 42 does not = 518.) No antithrombotic therapy was used (or status unknown) in 9.1% of patients.
      Table 7Antithrombotic Prescription at Inclusion and at Discharge When the Following Pharmacologic Cardioversion Was Performed at the Time of Survey or Planned at Discharge
      Pharmacologic Cardioversion
      Performed (n = 750)Planned (n = 13)
      InclusionDischargeInclusionDischarge
      N%N%N%N%
      None and unknown28638.1689.1215.400.0
      OAC alone18825.128037.3861.5369.2
      Antiplatelet alone19025.314719.6215.400.0
      OAC + antiplatelet668.822029.317.7023.1
      Others
      Others include OAC + other antithrombotic therapy, antiplatelet + other antithrombotic therapy, OAC + antiplatelet + other antithrombotic therapy and other antithrombotic therapy (fondaparinux, low-molecular weight heparin, unfractionated heparin, other).
      202.7354.70007.7
      Total750100.0750100.013100.03100.0
      Vitamin K Antagonists or Novel Oral Anticoagulation Use
      PerformedPlanned
      Inclusion (N)Discharge (N)Inclusion (N)Discharge (N)
      VKANOACTotalVKANOACTotalVKANOACTotalVKANOACTotal
      OAC alone1701818824832280628639
      OAC + antiplatelet615662129220101303
      OAC + others
      Others include OAC + other antithrombotic therapy and OAC + antiplatelet + other antithrombotic therapy.
      41517118000101
      Total235242594774251872910313
      NOAC = novel oral anticoagulation; OAC = oral anticoagulation; VKA = vitamin K antagonist.
      Others include OAC + other antithrombotic therapy, antiplatelet + other antithrombotic therapy, OAC + antiplatelet + other antithrombotic therapy and other antithrombotic therapy (fondaparinux, low-molecular weight heparin, unfractionated heparin, other).
      Others include OAC + other antithrombotic therapy and OAC + antiplatelet + other antithrombotic therapy.
      Figure thumbnail gr1
      Figure 1Antithrombotic drug prescription at inclusion and discharge when the following interventions were performed at the time of the survey or planned at discharge: pharmacologic cardioversion (A), electrical cardioversion (B), or catheter ablation (C). AP = antiplatelet; OAC = oral anticoagulation.
      For patients in whom electrical cardioversion was performed or planned (n = 703), oral anticoagulation was used in the majority (at least 85.5% at discharge in those in whom electrical cardioversion performed, or at least 90.2% when planned). No antiplatelet therapy was used when oral anticoagulation was planned (Table 8, Figure 1). In patients undergoing electrical cardioversion who received oral anticoagulation, vitamin K antagonist therapy was prescribed in the majority (86.3%, 466/540 at discharge), whereas novel oral anticoagulants were used in the minority (13.7%, 74/540 at discharge). No antithrombotic therapy was used (or status unknown) in 4.9% of patients.
      Table 8Antithrombotic Prescription at Inclusion and at Discharge When the Following Electrical Cardioversion Was Performed at the Time of Survey or Planned at Discharge
      Electrical Cardioversion
      Performed (n = 612)Planned (n = 91)
      InclusionDischargeInclusionDischarge
      N%N%N%N%
      None and unknown6410.5233.82325.311.1
      OAC alone40666.343070.34145.17481.3
      Antiplatelet alone457.4376.11920.900.0
      OAC + antiplatelet8513.99315.266.688.8
      Others
      Others include OAC + other antithrombotic therapy, antiplatelet + other antithrombotic therapy, OAC + antiplatelet + other antithrombotic therapy and other antithrombotic therapy (fondaparinux, low-molecular-weight heparin, unfractionated heparin, other).
      122.0294.722.288.8
      Total612100.0612100.091100.091100.0
      VKA or NOAC Use
      PerformedPlanned
      Inclusion (N)Discharge (N)Inclusion (N)Discharge (N)
      VKANOACTotalVKANOACTotalVKANOACTotalVKANOACTotal
      OAC alone350564063646643038341641074
      OAC + antiplatelet7878585893606808
      OAC + others
      Others include OAC + other antithrombotic therapy and OAC + antiplatelet + other antithrombotic therapy.
      10117017000505
      Total429634924667454044347771087
      NOAC = novel oral anticoagulation; OAC = oral anticoagulation; VKA = vitamin K antagonist.
      Others include OAC + other antithrombotic therapy, antiplatelet + other antithrombotic therapy, OAC + antiplatelet + other antithrombotic therapy and other antithrombotic therapy (fondaparinux, low-molecular-weight heparin, unfractionated heparin, other).
      Others include OAC + other antithrombotic therapy and OAC + antiplatelet + other antithrombotic therapy.
      Among patients in whom catheter ablation was performed or planned, oral anticoagulation was used in the majority (at least 88.1% at discharge among those in whom ablation performed, or at least 73.3% when planned) (Table 9). In the patients who underwent ablation and received oral anticoagulation, vitamin K antagonist therapy was prescribed in the majority (88.1%, 148/168 at discharge), whereas novel oral anticoagulants were used in the minority (11.9%, 20/168 at discharge). No antithrombotic therapy was used in 7.1% (2.7% performed and 4.4% planned).
      Table 9Antithrombotic Prescription at Inclusion and at Discharge When the Following Catheter Ablation Was Performed at the Time of Survey or Planned at Discharge
      Catheter Ablation
      Performed (n = 186)Planned (n = 45)
      InclusionDischargeInclusionDischarge
      N%N%N%N%
      None and unknown31.652.7511.124.4
      OAC alone15985.515583.33066.72862.2
      Antiplatelet alone105.494.824.424.4
      OAC + antiplatelet84.394.8511.1511.1
      Others
      Others include OAC + other antithrombotic therapy, antiplatelet + other antithrombotic therapy, OAC + antiplatelet + other antithrombotic therapy and other antithrombotic therapy (fondaparinux, low-molecular weight heparin, unfractionated heparin, other).
      63.284.336.7817.8
      Total186100.0186100.045100.045100.0
      VKA or NOAC Use
      PerformedPlanned
      Inclusion (N)Discharge (N)Inclusion (N)Discharge (N)
      VKANOACTotalVKANOACTotalVKANOACTotalVKANOACTotal
      OAC alone14118159138171552733024428
      OAC + antiplatelet628639415505
      OAC + others
      Others include OAC + other antithrombotic therapy and OAC + antiplatelet + other antithrombotic therapy.
      303404000505
      Total15020170148201683143534438
      NOAC = novel oral anticoagulation; OAC = oral anticoagulation; VKA = vitamin K antagonist.
      Others include OAC + other antithrombotic therapy, antiplatelet + other antithrombotic therapy, OAC + antiplatelet + other antithrombotic therapy and other antithrombotic therapy (fondaparinux, low-molecular weight heparin, unfractionated heparin, other).
      Others include OAC + other antithrombotic therapy and OAC + antiplatelet + other antithrombotic therapy.

      Discussion

      In this report from the EORP-AF Pilot Survey, we found that oral anticoagulation often was used for atrial fibrillation, especially when heart failure or other cardiac diseases were present. However, antiplatelet therapy still was prescribed routinely with or without oral anticoagulation when there was coexistent myocardial infarction or coronary artery disease. Oral anticoagulation was prescribed less often in elderly patients, and antiplatelet therapy alone was prescribed more commonly. When the CHA2DS2-VASc score was used, 95.58% of patients with a score ≥1 received oral anticoagulation.
      Often, oral anticoagulation was used for atrial fibrillation, usually when clinical heart failure or other cardiac disease was present. A clinical diagnosis of heart failure was not an independent predictor for stroke in the systematic review from the Stroke in Atrial Fibrillation Working Group
      Stroke-in-AF-Working-Group
      Independent predictors of stroke in patients with atrial fibrillation: a systematic review.
      or the Swedish atrial fibrillation cohort study.
      • Friberg L.
      • Rosenqvist M.
      • Lip G.Y.
      Evaluation of risk stratification schemes for ischaemic stroke and bleeding in 182 678 patients with atrial fibrillation: the Swedish Atrial Fibrillation cohort study.
      However, the presence of moderate-severe systolic impairment on 2-dimensional echocardiography is an independent predictor of stroke.
      Echocardiographic predictors of stroke in patients with atrial fibrillation: a prospective study of 1066 patients from 3 clinical trials.
      The “C” in CHA2DS2-VASc has been defined as referring to the presence of moderate-severe systolic impairment or recent decompensation irrespective of ejection fraction, given that such patients are still at high risk of thromboembolism.
      • Banerjee A.
      • Taillandier S.
      • Olesen J.B.
      • et al.
      Ejection fraction and outcomes in patients with atrial fibrillation and heart failure: the Loire Valley Atrial Fibrillation Project.
      Often, antiplatelet therapy was prescribed with or without oral anticoagulation when there was coexistent myocardial infarction or coronary artery disease. Antiplatelet monotherapy also was prescribed regularly in such patients. The presence of vascular disease independently increases the risk of stroke in atrial fibrillation.
      • Friberg L.
      • Rosenqvist M.
      • Lip G.Y.
      Evaluation of risk stratification schemes for ischaemic stroke and bleeding in 182 678 patients with atrial fibrillation: the Swedish Atrial Fibrillation cohort study.
      • Anandasundaram B.
      • Lane D.A.
      • Apostolakis S.
      • Lip G.Y.
      The impact of atherosclerotic vascular disease in predicting a stroke, thromboembolism and mortality in atrial fibrillation patients: a systematic review.
      Thus, in patients with atrial fibrillation with stable vascular disease, oral anticoagulation is the preferred treatment option, because combination therapy does not reduce thromboembolism but substantially increases the risk of major bleeding, especially intracranial hemorrhage.
      • Lip G.Y.
      Don't add aspirin for associated stable vascular disease in a patient with atrial fibrillation receiving anticoagulation.
      The situation is complex in patients with atrial fibrillation presenting with an acute coronary syndrome or undergoing angioplasty or stenting, with guidelines recommending a period of triple therapy, followed by oral anticoagulation plus single antiplatelet, and then oral anticoagulation alone.
      • Marin F.
      • Huber K.
      • Lip G.Y.
      Antithrombotic therapy in atrial fibrillation and stent implantation: treatment or threats by the use of triple or dual antithrombotic therapy.
      • Bernard A.
      • Fauchier L.
      • Pellegrin C.
      • et al.
      Anticoagulation in patients with atrial fibrillation undergoing coronary stent implantation.
      Recent data from a small randomized trial and a nationwide cohort study suggest that oral anticoagulation plus clopidogrel would be sufficient for post–acute coronary syndrome treated with coronary stenting.
      • Dewilde W.J.
      • Oirbans T.
      • Verheugt F.W.
      • et al.
      Use of clopidogrel with or without aspirin in patients taking oral anticoagulant therapy and undergoing percutaneous coronary intervention: an open-label, randomised, controlled trial.
      Bleeding risk factors were similar between the different types of antithrombotic therapies used, except when oral anticoagulation was less commonly used in chronic kidney disease.
      • Marinigh R.
      • Lane D.A.
      • Lip G.Y.
      Severe renal impairment and stroke prevention in atrial fibrillation: implications for thromboprophylaxis and bleeding risk.
      Patients with chronic kidney disease and atrial fibrillation are at higher risk of thromboembolism, myocardial infarction, and death, as well as major bleeding.
      • Roldán V.
      • Marin F.
      • Manzano-Fernandez S.
      • et al.
      Does chronic kidney disease improve the predictive value of the CHADS2 and CHA2DS2-VASc stroke stratification risk scores for atrial fibrillation?.
      • Olesen J.B.
      • Lip G.Y.
      • Kamper A.L.
      • et al.
      Stroke and bleeding in atrial fibrillation with chronic kidney disease.
      As in the original Euro Heart Survey, oral anticoagulation was used less often in paroxysmal atrial fibrillation, although such patients remain at high risk of thromboembolism.
      • Hart R.G.
      • Pearce L.A.
      • Rothbart R.M.
      • McAnulty J.H.
      • Asinger R.W.
      • Halperin J.L.
      Stroke with intermittent atrial fibrillation: incidence and predictors during aspirin therapy. Stroke prevention in atrial fibrillation investigators.
      • Nieuwlaat R.
      • Dinh T.
      • Olsson S.B.
      • et al.
      Should we abandon the common practice of withholding oral anticoagulation in paroxysmal atrial fibrillation?.
      Indeed, guidelines emphasize that in the presence of stroke risk factors, oral anticoagulation should be prescribed irrespective of the clinical type of atrial fibrillation (paroxysmal, persistent, permanent).
      • Camm A.J.
      • Lip G.Y.
      • De Caterina R.
      • et al.
      2012 focused update of the ESC Guidelines for the management of atrial fibrillation: an update of the 2010 ESC Guidelines for the management of atrial fibrillation–developed with the special contribution of the European Heart Rhythm Association.
      There was a tendency for oral anticoagulation to be prescribed less in younger patients and for antiplatelet therapy alone to be prescribed more in the elderly. In the trials with elderly patients, oral anticoagulation was associated with a significant reduction in thromboembolism, and the risks of major bleeding or adverse effects were similar or higher with aspirin compared with warfarin in the elderly.
      • Mant J.
      • Hobbs F.D.
      • 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.
      • Rash A.
      • Downes T.
      • Portner R.
      • Yeo W.W.
      • Morgan N.
      • Channer K.S.
      A randomised controlled trial of warfarin versus aspirin for stroke prevention in octogenarians with atrial fibrillation (WASPO).
      Antiplatelet therapy was used more often in patients with a high HAS-BLED score, perhaps because of the perception that aspirin was a safer alternative than oral anticoagulants. The evidence is clear that the risk of major bleeding (or intracranial bleeding) with aspirin is not significantly different than with oral anticoagulation, especially in the elderly.
      • Lip G.Y.
      The role of aspirin for stroke prevention in atrial fibrillation.
      Thus, recent treatment guidelines from Europe and North America have downgraded the role of aspirin for stroke prevention in atrial fibrillation, given its limited (or lack of) efficacy and poor safety.
      • Camm A.J.
      • Lip G.Y.
      • De Caterina R.
      • et al.
      2012 focused update of the ESC Guidelines for the management of atrial fibrillation: an update of the 2010 ESC Guidelines for the management of atrial fibrillation–developed with the special contribution of the European Heart Rhythm Association.
      • You J.J.
      • Singer D.E.
      • Howard P.A.
      • et al.
      Antithrombotic therapy for atrial fibrillation: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-based Clinical Practice Guidelines.
      In the whole cohort, the most common risk factors for stroke were heart failure and hypertension. This is in keeping with various epidemiologic datasets or surveys in which heart failure and hypertension were the most common etiologic factors for atrial fibrillation and contributed to its thromboembolic complications.
      • Wilke T.
      • Groth A.
      • Mueller S.
      • et al.
      Oral anticoagulation use by patients with atrial fibrillation in Germany. Adherence to guidelines, causes of anticoagulation under-use and its clinical outcomes, based on claims-data of 183,448 patients.
      • Kirchhof P.
      • Ammentorp B.
      • Darius H.
      • et al.
      Management of atrial fibrillation in seven European countries after the publication of the 2010 ESC Guidelines on atrial fibrillation: primary results of the PREvention oF thromboemolic events–European Registry in Atrial Fibrillation (PREFER in AF).
      On the basis of the CHADS2 score, 89.34% of patients with a score ≥1 received oral anticoagulation. When the CHA2DS2-VASc score was used, 95.58% with a score ≥1 received oral anticoagulation, and 83.67% of those with a score ≥2 received oral anticoagulation. This is an improvement over reported data in the Euro Heart Survey,
      • 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.
      with an increase of oral anticoagulation use among cardiologists. Indeed, this may reflect the introduction of new guidelines. In the 2012 focused update of the ESC guideline, the initial decision step is to identify “low-risk” patients who did not require any antithrombotic therapy (ie, aged <65 years and lone atrial fibrillation; otherwise a CHA2DS2-VASc score = 0 [male] or CHA2DS2-VASc score = 1 [female]).
      • Camm A.J.
      • Lip G.Y.
      • De Caterina R.
      • et al.
      2012 focused update of the ESC Guidelines for the management of atrial fibrillation: an update of the 2010 ESC Guidelines for the management of atrial fibrillation–developed with the special contribution of the European Heart Rhythm Association.
      • Lip G.Y.
      Recommendations for thromboprophylaxis in the 2012 focused update of the ESC Guidelines on Atrial Fibrillation: a commentary.
      Subsequent to this step, patients with ≥1 stroke risk factors can be offered effective stroke prevention, which is oral anticoagulation, whether given as well-controlled vitamin K antagonist therapy (with a long time in the therapeutic range, >70%
      • De Caterina R.
      • Husted S.
      • Wallentin L.
      • et al.
      Vitamin K antagonists in heart disease: current status and perspectives (Section III). Position paper of the ESC Working Group on Thrombosis - Task Force on Anticoagulants in Heart Disease.
      ) or one of the novel oral anticoagulants.
      Despite a preference for the use of novel oral anticoagulants in the ESC guidelines, they were prescribed in the minority, but this survey shows their use particularly in patients with previous transient ischemic attack/stroke or rhythm control. Novel oral anticoagulants were used less in association with valvular heart disease, heart failure, and vascular disease; the latter may be due to concerns, particularly with dabigatran, in patients with associated coronary artery disease.
      • Uchino K.
      • Hernandez A.V.
      Dabigatran association with higher risk of acute coronary events: meta-analysis of noninferiority randomized controlled trials.
      Novel oral anticoagulants should not be used in patients with hemodynamically significant valvular heart disease or prosthetic mechanical valves.
      • Eikelboom J.W.
      • Connolly S.J.
      • Brueckmann M.
      • et al.
      Dabigatran versus warfarin in patients with mechanical heart valves.
      Wider use of novel oral anticoagulants would have implications for improved stroke-prevention outcomes in Europe, given their relative efficacy, safety, and convenience compared with vitamin K antagonists, which ultimately lead to a greater net clinical benefit overall.
      • Banerjee A.
      • Lane D.A.
      • Torp-Pedersen C.
      • Lip G.Y.
      Net clinical benefit of new oral anticoagulants (dabigatran, rivaroxaban, apixaban) versus no treatment in a ‘real world’ atrial fibrillation population: a modelling analysis based on a nationwide cohort study.
      • Pisters R.
      • Nieuwlaat R.
      • Lane D.A.
      • Crijns H.J.
      • Lip G.Y.
      Potential net clinical benefit of population-wide implementation of apixaban and dabigatran among European patients with atrial fibrillation. A modelling analysis from the Euro Heart Survey.
      In addition, not all the novel oral anticoagulants were available in some participating countries at the time of data collection.
      Oral anticoagulation also is needed in the setting of rhythm-control therapy. Pharmacologic and electrical cardioversion were planned or performed in 763 and 703 subjects, respectively, whereas catheter ablation and oral anticoagulation were used in the majority. The proportion in whom oral anticoagulation was not used could be explained by the proportion of patients with new-onset atrial fibrillation in whom oral anticoagulation is not initiated in some countries when early conversion to sinus rhythm is achieved. Nonetheless, the ESC guidelines do recommend that oral anticoagulation should be used in the presence of stroke risk factors, irrespective of whether a successful rhythm-control strategy (ie, cardioversion or ablation) is achieved.
      • Camm A.J.
      • Lip G.Y.
      • De Caterina R.
      • et al.
      2012 focused update of the ESC Guidelines for the management of atrial fibrillation: an update of the 2010 ESC Guidelines for the management of atrial fibrillation–developed with the special contribution of the European Heart Rhythm Association.

      Study Limitations

      We did not have data on the quality of anticoagulation control or on the time in therapeutic range, which is highly relevant given that the latter is a major determinant of thromboembolism, bleeding, and death in patients treated with vitamin K antagonists.
      • Gallego P.
      • Roldan V.
      • Marin F.
      • et al.
      Cessation of oral anticoagulation in relation to mortality and the risk of thrombotic events in patients with atrial fibrillation.
      Also, we did not have detailed data on biochemical parameters or outcomes, which will be addressed by the ongoing follow-up phase of the EORP-AF Pilot, to be reported in late 2014.

      Conclusions

      The EORP-AF Pilot Survey provides contemporary data on oral anticoagulation prescribing by European cardiologists for atrial fibrillation. Although the uptake of oral anticoagulation (mostly vitamin K antagonist therapy) has improved since the Euro Heart Survey a decade ago, antiplatelet therapy still is prescribed routinely with or without oral anticoagulation, whereas elderly patients often are undertreated with oral anticoagulation.

      Acknowledgments

      Executive steering committee, Steering Committee (National Coordinators), and Study Investigators were listed in the primary article describing the baseline data, by Lip et al.
      • Lip G.Y.
      • Laroche C.
      • Dan G.A.
      • et al.
      A prospective survey in European Society of Cardiology member countries of atrial fibrillation management: baseline results of EURObservational Research Programme Atrial Fibrillation (EORP-AF) Pilot General Registry.
      Data monitor and technical support team: Data collection was conducted by the EURObservational Research Program department from the European Cardiac Society by Viviane Missiamenou. Statistical analyses were performed by Cécile Laroche with the support of Renato Urso. Overall activities were coordinated by Aldo P. Maggioni (Scientific Coordinator, EORP) and Thierry Ferreira (Head of Department, EORP).

      Appendix

      Supplementary Table 1Characteristics of Patients in Whom an Intervention to Restore Sinus Rhythm Was Performed or Planned
      Pharmacologic CardioversionElectrical CardioversionCatheter Ablation
      N = 763N = 703N = 231
      PerformedPlannedPerformedPlannedPerformedPlanned
      N = 750N = 13N = 612N = 91N = 186N = 45
      Demographics:
       Age (y) (mean ± SD)67.9 ± 11.768.2 ± 9.266.0 ± 11.364.2 ± 9.859.4 ± 10.862.9 ± 9.0
       Age (y) (median, IQR)69.0 (61.0-76.0)65.0 (63.0-74.0)67.0 (59.0-74.0)64.0 (59.0-71.0)61.0 (53.0-67.0)62.0 (57.0-70.0)
       Female gender (%)46.2730.7734.3128.5735.4840.00
      Duration of current AF episode (%):
       <24 h40.4015.3822.715.4930.1126.67
       24 h to 7 d18.677.6914.5419.788.6015.56
       >7 d27.8753.8548.3763.7425.8133.33
       Unknown13.0723.0814.3810.9935.4824.44
      CHA2DS2-VASc (%):
       0 (all) and 1 (female)8.9315.3811.609.8927.4217.78
       1 (male)8.5315.3818.4626.3724.196.67
       2 and more (all)82.5369.2369.9363.7448.3975.56
      AF = atrial fibrillation; CHA2DS2-VASc = Congestive heart failure, Hypertension, Age ≥75 [Doubled], Diabetes, Stroke [Doubled]-Vascular disease, Age 65-74, and Sex category [female]; IQR = interquartile range; SD = standard deviation.

      References

        • Banerjee A.
        • Marin F.
        • Lip G.Y.
        The improved but unfinished business of stroke risk stratification in atrial fibrillation.
        Rev Esp Cardiol. 2011; 64: 639-641
        • 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
        • Camm A.J.
        • Lip G.Y.
        • De Caterina R.
        • et al.
        2012 focused update of the ESC Guidelines for the management of atrial fibrillation: an update of the 2010 ESC Guidelines for the management of atrial fibrillation–developed with the special contribution of the European Heart Rhythm Association.
        Europace. 2012; 14: 1385-1413
        • Lip G.Y.
        • Nieuwlaat R.
        • Pisters R.
        • Lane D.A.
        • Crijns H.J.
        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
        • Pisters R.
        • Lane D.A.
        • Nieuwlaat R.
        • de Vos C.B.
        • Crijns H.J.
        • Lip G.Y.
        A novel user-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in patients with atrial fibrillation: the Euro Heart Survey.
        Chest. 2010; 138: 1093-1100
        • Kornej J.
        • Potpara T.
        • Lip G.Y.
        Anticoagulation management in non-valvular atrial fibrillation: current and future directions.
        Pol Arch Med Wewn. 2013; 123: 623-634
        • Ogawa S.
        • Aonuma K.
        • Tse H.F.
        • et al.
        The APHRS's 2013 statement on antithrombotic therapy of patients with nonvalvular atrial fibrillation.
        J Arrhythmia. 2013; 29: 190-200
        • You J.J.
        • Singer D.E.
        • Howard P.A.
        • et al.
        Antithrombotic therapy for atrial fibrillation: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-based Clinical Practice Guidelines.
        Chest. 2012; 141: e531S-e575S
        • Skanes A.
        • Healey J.
        • Cairns J.
        • et al.
        Focused 2012 update of the Canadian Cardiovascular Society Atrial Fibrillation Guidelines: recommendations for stroke prevention and rate/rhythm control.
        Can J Cardiol. 2012; 28: 125-136
        • Fuster V.
        • Ryden L.E.
        • Cannom D.S.
        • et al.
        2011 ACCF/AHA/HRS focused updates incorporated into the ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation: a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines developed in partnership with the European Society of Cardiology and in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society.
        J Am Coll Cardiol. 2011; 57: e101-e198
        • Lip G.Y.
        • Laroche C.
        • Dan G.A.
        • et al.
        A prospective survey in European Society of Cardiology member countries of atrial fibrillation management: baseline results of EURObservational Research Programme Atrial Fibrillation (EORP-AF) Pilot General Registry.
        Europace. 2013 Dec 17; ([Epub ahead of print])
        • Stroke-in-AF-Working-Group
        Independent predictors of stroke in patients with atrial fibrillation: a systematic review.
        Neurology. 2007; 69: 546-554
        • Friberg L.
        • Rosenqvist M.
        • Lip G.Y.
        Evaluation of risk stratification schemes for ischaemic stroke and bleeding in 182 678 patients with atrial fibrillation: the Swedish Atrial Fibrillation cohort study.
        Eur Heart J. 2012; 33: 1500-1510
      1. Echocardiographic predictors of stroke in patients with atrial fibrillation: a prospective study of 1066 patients from 3 clinical trials.
        Arch Intern Med. 1998; 158: 1316-1320
        • Banerjee A.
        • Taillandier S.
        • Olesen J.B.
        • et al.
        Ejection fraction and outcomes in patients with atrial fibrillation and heart failure: the Loire Valley Atrial Fibrillation Project.
        Eur J Heart Fail. 2012; 14: 295-301
        • Anandasundaram B.
        • Lane D.A.
        • Apostolakis S.
        • Lip G.Y.
        The impact of atherosclerotic vascular disease in predicting a stroke, thromboembolism and mortality in atrial fibrillation patients: a systematic review.
        J Thromb Haemost. 2013; 11: 975-987
        • Lip G.Y.
        Don't add aspirin for associated stable vascular disease in a patient with atrial fibrillation receiving anticoagulation.
        BMJ. 2008; 336: 614-615
        • Marin F.
        • Huber K.
        • Lip G.Y.
        Antithrombotic therapy in atrial fibrillation and stent implantation: treatment or threats by the use of triple or dual antithrombotic therapy.
        Thromb Haemost. 2013; 110: 623-625
        • Bernard A.
        • Fauchier L.
        • Pellegrin C.
        • et al.
        Anticoagulation in patients with atrial fibrillation undergoing coronary stent implantation.
        Thromb Haemost. 2013; 110: 560-568
        • Dewilde W.J.
        • Oirbans T.
        • Verheugt F.W.
        • et al.
        Use of clopidogrel with or without aspirin in patients taking oral anticoagulant therapy and undergoing percutaneous coronary intervention: an open-label, randomised, controlled trial.
        Lancet. 2013; 381: 1107-1115
        • Marinigh R.
        • Lane D.A.
        • Lip G.Y.
        Severe renal impairment and stroke prevention in atrial fibrillation: implications for thromboprophylaxis and bleeding risk.
        J Am Coll Cardiol. 2011; 57: 1339-1348
        • Roldán V.
        • Marin F.
        • Manzano-Fernandez S.
        • et al.
        Does chronic kidney disease improve the predictive value of the CHADS2 and CHA2DS2-VASc stroke stratification risk scores for atrial fibrillation?.
        Thromb Haemost. 2013; 109: 956-960
        • Olesen J.B.
        • Lip G.Y.
        • Kamper A.L.
        • et al.
        Stroke and bleeding in atrial fibrillation with chronic kidney disease.
        N Engl J Med. 2012; 367: 625-635
        • Hart R.G.
        • Pearce L.A.
        • Rothbart R.M.
        • McAnulty J.H.
        • Asinger R.W.
        • Halperin J.L.
        Stroke with intermittent atrial fibrillation: incidence and predictors during aspirin therapy. Stroke prevention in atrial fibrillation investigators.
        J Am Coll Cardiol. 2000; 35: 183-187
        • Nieuwlaat R.
        • Dinh T.
        • Olsson S.B.
        • et al.
        Should we abandon the common practice of withholding oral anticoagulation in paroxysmal atrial fibrillation?.
        Eur Heart J. 2008; 29: 915-922
        • Mant J.
        • Hobbs F.D.
        • 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
        • Rash A.
        • Downes T.
        • Portner R.
        • Yeo W.W.
        • Morgan N.
        • Channer K.S.
        A randomised controlled trial of warfarin versus aspirin for stroke prevention in octogenarians with atrial fibrillation (WASPO).
        Age Ageing. 2007; 36: 151-156
        • Lip G.Y.
        The role of aspirin for stroke prevention in atrial fibrillation.
        Nat Rev Cardiol. 2011; 8: 602-606
        • Wilke T.
        • Groth A.
        • Mueller S.
        • et al.
        Oral anticoagulation use by patients with atrial fibrillation in Germany. Adherence to guidelines, causes of anticoagulation under-use and its clinical outcomes, based on claims-data of 183,448 patients.
        Thromb Haemost. 2012; 107: 1053-1065
        • Kirchhof P.
        • Ammentorp B.
        • Darius H.
        • et al.
        Management of atrial fibrillation in seven European countries after the publication of the 2010 ESC Guidelines on atrial fibrillation: primary results of the PREvention oF thromboemolic events–European Registry in Atrial Fibrillation (PREFER in AF).
        Europace. 2014; 16: 6-14
        • Lip G.Y.
        Recommendations for thromboprophylaxis in the 2012 focused update of the ESC Guidelines on Atrial Fibrillation: a commentary.
        J Thromb Haemost. 2013; 11: 615-626
        • De Caterina R.
        • Husted S.
        • Wallentin L.
        • et al.
        Vitamin K antagonists in heart disease: current status and perspectives (Section III). Position paper of the ESC Working Group on Thrombosis - Task Force on Anticoagulants in Heart Disease.
        Thromb Haemost. 2013; 110: 1087-1107
        • Uchino K.
        • Hernandez A.V.
        Dabigatran association with higher risk of acute coronary events: meta-analysis of noninferiority randomized controlled trials.
        Arch Intern Med. 2012; 172: 397-402
        • Eikelboom J.W.
        • Connolly S.J.
        • Brueckmann M.
        • et al.
        Dabigatran versus warfarin in patients with mechanical heart valves.
        N Engl J Med. 2013; 369: 1206-1214
        • Banerjee A.
        • Lane D.A.
        • Torp-Pedersen C.
        • Lip G.Y.
        Net clinical benefit of new oral anticoagulants (dabigatran, rivaroxaban, apixaban) versus no treatment in a ‘real world’ atrial fibrillation population: a modelling analysis based on a nationwide cohort study.
        Thromb Haemost. 2012; 107: 584-589
        • Pisters R.
        • Nieuwlaat R.
        • Lane D.A.
        • Crijns H.J.
        • Lip G.Y.
        Potential net clinical benefit of population-wide implementation of apixaban and dabigatran among European patients with atrial fibrillation. A modelling analysis from the Euro Heart Survey.
        Thromb Haemost. 2013; 109: 328-336
        • Gallego P.
        • Roldan V.
        • Marin F.
        • et al.
        Cessation of oral anticoagulation in relation to mortality and the risk of thrombotic events in patients with atrial fibrillation.
        Thromb Haemost. 2013; 110: 1189-1198