For example, transcatheter mitral valve interventions (eg, to include both MitraClip and Mitral valve replacement) are emerging as a possible but more data are awaited, especially in relation to OAC use. Also, EHRA type 1 is broadly similar to the previously described mechanical and rheumatic mitral valvular AF (MARM-AF).444 Nondrug Alternatives and Perioperative Considerations Occlusion of the LAA With Devices or Surgical Techniques: Approximately 90% of the thrombi found in patients with non-valvular AF and 57% of the thrombi found in valvular AF are located in the LAA.445 TABLE 11 ] Summary Box: EHRA Categorization in Relation to the Type of OAC Used in Patients With AF De nition EHRA type 1 VHD AF patients with VHD needing therapy with a vitamin K antagonist (VKA)  Mitral stenosis (moderate-severe, of rheumatic origin)  Mechanical prosthetic valve replacement EHRA type 2 VHD AF patients with VHD needing therapy with a VKA or an NOAC, also taking into consideration CHA2DS2-VASc score risk factor components  Mitral regurgitation  Mitral valve repair  Aortic stenosis  Aortic regurgitation  Tricuspid regurgitation  Tricuspid stenosis  Pulmonary regurgitation  Pulmonic stenosis  Bioprosthetic valve replacements  Trans-aortic valve intervention CHA2DS2-VASc congestive heart failure, hypertension, age $ 75 (doubled), diabetes, stroke (doubled)-vascular disease, age 65-74 and sex category (female); EHRA Evaluated Heart Valves, Rheumatic or Arti cial; VHD valvular heart disease. See Table 1 legend for expansion of other abbreviations.


Also, EHRA type 1 is broadly similar to the previously described mechanical and rheumatic mitral valvular AF (MARM-AF).444 Nondrug Alternatives and Perioperative Considerations Occlusion of the LAA With Devices or Surgical Techniques: Approximately 90% of the thrombi found in patients with non-valvular AF and 57% of the thrombi found in valvular AF are located in the LAA.445 TABLE 11 ] Summary Box: EHRA Categorization in Relation to the Type of OAC Used in Patients With AF De nition EHRA type 1 VHD AF patients with VHD needing therapy with a vitamin K antagonist (VKA)  Mitral stenosis (moderate-severe, of rheumatic origin)  Mechanical prosthetic valve replacement EHRA type 2 VHD AF patients with VHD needing therapy with a VKA or an NOAC, also taking into consideration CHA2DS2-VASc score risk factor components  Mitral regurgitation  Mitral valve repair  Aortic stenosis  Aortic regurgitation  Tricuspid regurgitation  Tricuspid stenosis  Pulmonary regurgitation  Pulmonic stenosis  Bioprosthetic valve replacements  Trans-aortic valve intervention CHA2DS2-VASc congestive heart failure, hypertension, age $ 75 (doubled), diabetes, stroke (doubled)-vascular disease, age 65-74 and sex category (female); EHRA Evaluated Heart Valves, Rheumatic or Arti cial; VHD valvular heart disease. See Table 1 legend for expansion of other abbreviations. LAAO using speci c percutaneous devices (WATCHMAN, Amplatzer Cardiac Plug, or WaveCrest device or the Lariat endocardial and epicardial ligation technique) or occlusion during a cardiac surgery procedure with either LAA amputation and closure or a stapler device have been proposed and tested for patients with AF at high risk of stroke in the presence of a high risk of bleeding or in the presence of contraindications to OACs.


LAAO using speci c percutaneous devices (WATCHMAN, Amplatzer Cardiac Plug, or WaveCrest device or the Lariat endocardial and epicardial ligation technique) or occlusion during a cardiac surgery procedure with either LAA amputation and closure or a stapler device have been proposed and tested for patients with AF at high risk of stroke in the presence of a high risk of bleeding or in the presence of contraindications to OACs. Two randomized studies evaluated the WATCHMAN (Atritech, Inc) device vs warfarin: the Watchman Left Atrial Appendage System for Embolic Protection in Patients with Atrial Fibrillation (PROTECT AF) and the Evaluation of the WATCHMAN LAA Closure Device in Patients With Atrial Fibrillation Versus Long Term Warfarin Therapy (PREVAIL AF).446-452 In the PROTECT AF trial, the ef cacy of LAA closure with the device met the pre-speci ed criteria for non-inferiority vs warfarin, but the rate of adverse safety events in the intervention group was 4.4% with evidence of harmful periprocedural complications (pericardial effusion and procedure-related ischemic stroke).


Two randomized studies evaluated the WATCHMAN (Atritech, Inc) device vs warfarin: the Watchman Left Atrial Appendage System for Embolic Protection in Patients with Atrial Fibrillation (PROTECT AF) and the Evaluation of the WATCHMAN LAA Closure Device in Patients With Atrial Fibrillation Versus Long Term Warfarin Therapy (PREVAIL AF).446-452 In the PROTECT AF trial, the ef cacy of LAA closure with the device met the pre-speci ed criteria for non-inferiority vs warfarin, but the rate of adverse safety events in the intervention group was 4.4% with evidence of harmful periprocedural complications (pericardial effusion and procedure-related ischemic stroke). For acute complications, a learning curve appeared to be present, with serious pericardial effusions (requiring drainage) in 7.1% of the rst 3 implant patients at each site compared with 4.4% of subsequent patients.453 The serious complication rate of about 7% has been reported also for rst- or second-generation Amplatzer A recent systematic review network meta-analysis on the use of OACs and the Watchman device showed that the use of VKA, NOAC, and the Watchman device signi cantly reduce the risk of any stroke and systemic embolism as compared with placebo/control (Watchman device OR, 0.35; 95% CI, Data on the use of the WATCHMAN device in patients with contraindications to anticoagulation are very limited, and DAPT is needed for at least 6 weeks after the procedure, potentially exposing the patient to increased risk of bleeding.453 The Lariat device is based on an epicardial snare that requires positioning using a percutaneous approach to the epicardium through a pericardial access and in combination a percutaneous endocardial approach. In inexperienced operators, incomplete occlusion of the LAA after LARIAT ligation was relatively common (20% of cases) and was associated with risk of No randomized controlled study comparing this device with oral anticoagulation is currently available.


In inexperienced operators, incomplete occlusion of the LAA after LARIAT ligation was relatively common (20% of cases) and was associated with risk of No randomized controlled study comparing this device with oral anticoagulation is currently available. In addition, the role of LAAO devices in AF patients also has to consider that no trials are available comparing these devices with NOACs. Thrombus formation on LAAO devices is also not uncommon (as high as 7.2% per year) and is associated with a risk of ischemic stroke during follow-up.458,459 Different surgical techniques have been applied for surgical exclusion of LAA (simple suture ligation, over- sewing of the LAA base without excision, appendage excision or amputation, surgical stapling), but data on TEE during follow-up suggest incomplete occlusion in up These observations and the lack of a clear bene t on stroke prevention evident from an RCT indicate that in patients with AF, these surgical techniques do not currently allow avoidance or interruption of oral anticoagulation in patients at risk of Recommendations 55. In patients with AF at high risk of ischemic stroke who have absolute contraindications for OAC, we suggest using LAA occlusion (Weak recommendation, low quality evidence). Remark: When taking into account LAAO as a potential option, the risk of bleeding related to antiplatelets agents that need to be prescribed in the rst months has to be considered and the possibility to use NOACs. 56. In AF patients at risk of ischemic stroke undergoing cardiac surgery, we suggest considering surgical exclusion of the LAA for stroke prevention, but the need for long-term OAC is unchanged (Weak recommendation, low quality evidence). Surgical Procedures and Interventions: Patients with AF on long-term prophylaxis with OACs may need surgical or interventional procedures that require appropriate management.


Surgical Procedures and Interventions: Patients with AF on long-term prophylaxis with OACs may need surgical or interventional procedures that require appropriate management. Since bleeding risk may obviously be increased by the anticoagulant effect, interrupting anticoagulation for an intervention or a procedure transiently exposes the patient to increased risk of thromboembolism. Appropriate management requires balancing reducing the risk of thromboembolism and preventing excessive procedure- related bleeding. In the NOAC RCTs, surgical or other invasive procedures were required during a follow up of around 2 years in one-quarter of patients in RE-LY and one-third of patients in ROCKET AF and ARISTOTLE.72-74 1186 Evidence-Based Medicine [ 1 5 4 # 5 C H E S T N O V E M B E R 2 0 1 8 ] General principles of management can be considered, to be combined with individual clinical judgment, but they are derived from consensus of experts, since no data from RCTs are available to guide clinical decision- making. The following steps are important for appropriate management:  Estimation of the bleeding risk associated with a speci c intervention/procedure. The risk of bleeding can be predicted by the type of intervention and by its need, urgent or elective. e-Table 23 classi es surgical and interventional procedures according to bleeding risk as well as thromboembolic risk.205,464,465 The direct consequence of this evaluation is that in- terventions or procedure at very low bleeding risk, such as simple dental extractions or minor skin excision, can be planned and performed without interruption of oral anticoagulation. If the bleeding risk is substantial, then interruption of anticoagulation prior to the procedure intervention is needed to minimize the hemorrhagic risk, both in the intra-operative and immediate postoperative phase.  Estimation of patient thromboembolic risk.


If the bleeding risk is substantial, then interruption of anticoagulation prior to the procedure intervention is needed to minimize the hemorrhagic risk, both in the intra-operative and immediate postoperative phase.  Estimation of patient thromboembolic risk. Calcu- late the CHA2DS2-VASc score (low risk if 0 or 1) but an additional transient increase in risk has to be considered in case of recent stroke or recent pulmo- nary embolism.  Planning of the timing of anticoagulation inter- ruption. The timing of interruption is strictly dependent on the speci c anticoagulant the patient is receiving and CrCl. Important differences exist be- tween the management of patients treated with VKA The effect of warfarin can be monitored through INR; however, no standard labo- ratory test exists to measure the effect of NOACs. Discontinuation of warfarin is usually instituted 5 days before an elective surgical intervention, with INR checked the day before surgery, with the usual indication that surgery can be regularly planned if the INR is # 1.4 to 1.5 the day before surgery or the same day of surgery.465 For NOACs, the planning of interruption and resumption of therapy for surgical interventions/procedures is dependent on the type of procedure/intervention, the speci c agent used, and renal function, estimated by creatine clearance (using the Cockroft-Gault equation). In case of urgent sur- gery, reversal of anticoagulation or speci c measures may be required.205,466  Evaluation of the need for bridging. Pre-operative bridging can be considered in patients receiving VKA who are at particularly high risk of thromboembolism (eg, recent stroke, mechanical heart valve).465 In these cases, LMWH at therapeutic doses is usually pre- scribed starting 3 days before the procedure/inter- vention.


Pre-operative bridging can be considered in patients receiving VKA who are at particularly high risk of thromboembolism (eg, recent stroke, mechanical heart valve).465 In these cases, LMWH at therapeutic doses is usually pre- scribed starting 3 days before the procedure/inter- vention. Postoperative bridging includes administration of an LMWH when VKA is resumed in the postoperative period, with administration of both agents until achievement of a therapeutic INR. The role of bridging has been tested in a randomized trial, Bridging Anticoagulation in Patients who Require Temporary Interruption of Warfarin Ther- apy for an Elective Invasive Procedure or Surgery (BRIDGE), performed in patients on warfarin who were candidates for an invasive procedure (patients with mechanical valves were excluded).94 The risk of thromboembolism after the procedure was similar in patients with and without bridging, but the risk of major bleeding was higher in those who were bridged. Thus, we suggest that preoperative bridging is not required in AF patients treated with warfarin who do not have a particularly high risk of throm- boembolism and who do not have a mechanical valve.  In patients receiving NOACs, bridging is not required, but bridging could be considered in the postoperative phase if the patient cannot take oral medications for a prolonged period. Recommendations 57. In AF patients taking warfarin without high risk of thromboembolism or do not have a mechanical valve, we suggest preoperative management without bridging (Weak recommendation, low quality evidence). 58. In AF patients on antithrombotic prophylaxis with warfarin with a high risk of thromboembolism or with a mechanical valve, we suggest preoperative management with bridging (Weak recommendation, low quality evidence). 59. In AF patients on antithrombotic prophylaxis with an NOAC, we suggest preoperative management without bridging (Weak recommendation, low quality evidence).


In AF patients on antithrombotic prophylaxis with an NOAC, we suggest preoperative management without bridging (Weak recommendation, low quality evidence). The Patient Patient knowledge and understanding of the stroke risk associated with AF and the bene t of OAC to prevent stroke are crucial to patient acceptance of anticoagulants, as well as adherence, and life-long persistence (in most cases), to OAC. However, research demonstrates that AF patients generally have poor awareness and knowledge about their condition,467-472 medications used to treat AF, particularly OAC, and do not clearly comprehend the bene t/risk associated with stroke prevention regimens.203,468-471,473-478 Although there is increasing advocacy from clinical and expert consensus2,203,479 to incorporate patient preferences for treatment into the decision-making process, a patient s ability to make an informed decision may be hindered by their lack of understanding about the relationship between AF and stroke and the ef cacy/safety of OAC for stroke prevention, particularly at diagnosis, when these decisions are invariably addressed. Assessment of patient s knowledge (using the AF Knowledge or Jessa Atrial Fibrillation Knowledge ), as well as their values and preferences, could be undertaken to ascertain gaps to be lled; this may lead to better decision-making and improved adherence and persistence. Patient education is essential to provide patients with suf cient information to enable them to make an informed decision about whether they wish to take OAC, and if they do, which OAC they would prefer.203,476,482 Education needs to be tailored to the person s desire for information and their level of health literacy to promote patient understanding.


Patient education is essential to provide patients with suf cient information to enable them to make an informed decision about whether they wish to take OAC, and if they do, which OAC they would prefer.203,476,482 Education needs to be tailored to the person s desire for information and their level of health literacy to promote patient understanding. Recently, a prospective survey of 499 AF patients (with and without previous stroke) in the United States found that most (87%) desired more information about AF and how to reduce their risk of AF- AF patients perceive greater satisfaction with treatment if they are engaged in treatment decisions and provided with relevant information (verbal, visual, written, electronic/on-line resources, as appropriate, chosen by the patient), which is well communicated by their health-care providers,467,473,483 and updated over time. Full details on shared decision-making, patient preferences, and patient education/counseling are provided in e-Tables 24-26. Recommendations 60. In AF patients who have previously refused OAC, we suggest reinforcing educational messages at each contact with the patient and revisit OAC treatment decisions (Ungraded consensus-based statement). Remark: Patient and physician treatment objectives often differ signi cantly and it is important to elicit from the patient what outcomes of OAC treatment are important to them. Remark: Explain the risk of stroke and bene t/risks of treatment in terms the patient can understand and signpost the patient to appropriate educational resources Acknowledgments Financial/non nancial disclosure: See e-Table 1 for complete list of con icts of interest. Endorsements: This guideline has been endorsed by the AF Association, American College of Clinical Pharmacy (ACCP), Arrhythmia Alliance, and StopA b.org.


Endorsements: This guideline has been endorsed by the AF Association, American College of Clinical Pharmacy (ACCP), Arrhythmia Alliance, and StopA b.org. Other contributions: The authors would like to acknowledge Mellanie True Hills, founder of StopAFib.org, for her insights on patient values and preferences throughout the guideline development process and for contributing to the development of the patient education resources. Additional information: The e-Appendix, e-Figures, and e-Tables can be found in the Supplemental Materials section of the online article. References 1. Lip G, Freedman B, De Caterina R, Potpara TS. Stroke prevention in atrial brillation: past, present and future. Comparing the guidelines and practical decision-making. Thromb Haemost. 2017;117(7):1230-1239. 2. Lip GYH. The ABC pathway: an integrated approach to improve AF management. Nat Rev Cardiol. 2017;14(11):627-628. 3. You JJ, Singer DE, Howard PA, et al. Antithrombotic therapy for atrial brillation: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(suppl 2):e531S-e575S. 4. Gomez-Outes A, Lagunar-Ruiz J, Terleira-Fernandez AI, Calvo- Rojas G, Suarez-Gea ML, Vargas-Castrillon E. Causes of death in anticoagulated patients with atrial brillation. J Am Coll Cardiol. 2016;68(23):2508-2521. 5. Higgins J, Altman D, Sterne J, (editors). Chapter 8: Assessing risk of bias in included studies. In: Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from www.cochrane-handbook.org. 2011. 6. Sterne JA, Hern n MA, Reeves BC, et al. ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions. BMJ. 2016;355. 7. Diekemper RL, Ireland BK, Merz LR. Development of the Documentation and Appraisal Review Tool for systematic reviews. World J Meta-Anal. 2015;3(3):142-150. 8. Ozcan C, Strom JB, Newell JB, Mansour MC, Ruskin JN.


Ozcan C, Strom JB, Newell JB, Mansour MC, Ruskin JN. Incidence and predictors of atrial brillation and its impact on long-term survival in patients with supraventricular arrhythmias. Europace. 2014;16(10):1508-1514. 9. Higgins J, Altman D, Sterne J, (editors). Chapter 9: Analysing data and undertaking meta-analyses. In: Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. www.cochrane-handbook.org. 2011. 10. Balshem H, Helfand M, Sch nemann HJ, et al. GRADE guidelines: 3. Rating the quality of evidence. J Clin Epidemiol. 2011;64(4):401- 406. 11. Diekemper RL, Patel S, Mette SA, Ornelas J, Ouellette DR, Casey KR. Making the GRADE: CHEST updates its methodology. Chest. 2018;153(3):756-759. 12. Andrews J, Guyatt G, Oxman AD, et al. GRADE guidelines: 14. Going from evidence to recommendations: the signi cance and presentation of recommendations. J Clin Epidemiol. 2013;66(7): 719-725. 13. Lewis SZ, Diekemper R, Ornelas J, Casey KR. Methodologies for the development of CHEST guidelines and expert panel reports. Chest. 2014;146(1):182-192. 1188 Evidence-Based Medicine [ 1 5 4 # 5 C H E S T N O V E M B E R 2 0 1 8 ] 14. Jaeschke R; The GRADE Working Group. Use of GRADE grid to reach decisions on clinical practice guidelines when consensus is elusive. BMJ. 2008;337:327-330. 15. Lip GY, Fauchier L, Freedman SB, et al. Atrial brillation. Nat Rev Dis Primers. 2016;2:16016. 16. Lip GY, Brechin CM, Lane DA. The global burden of atrial brillation and stroke: a systematic review of the epidemiology of atrial brillation in regions outside North America and Europe. Chest. 2012;142(6):1489-1498. 17. Freedman B, Potpara TS, Lip GY. Stroke prevention in atrial brillation. Lancet. 2016;388(10046):806-817. 18. Allan V, Honarbakhsh S, Casas JP, et al. Are cardiovascular risk factors also associated with the incidence of atrial brillation?


Are cardiovascular risk factors also associated with the incidence of atrial brillation? A systematic review and eld synopsis of 23 factors in 32 population- based cohorts of 20 million participants. Thromb Haemost. 2017;117(5):837-850. 19. Moran PS, Teljeur C, Ryan M, Smith SM. Systematic screening for the detection of atrial brillation. Cochrane Database Syst Rev. 2016;(6):CD009586. 20. Amerena J, Chen SA, Sriratanasathavorn C, et al. Insights into management of atrial brillation in Asia Paci c gained from baseline data from REgistry on cardiac rhythm disORDers (RecordAF-Asia Paci c [AP]) registry. Am J Cardiol. 2012;109(3): 378-382. 21. Oldgren J, Healey JS, Ezekowitz M, et al. Variations in cause and management of atrial brillation in a prospective registry of 15,400 emergency department patients in 46 countries: the RE-LY Atrial Fibrillation Registry. Circulation. 2014;129(15):1568-1576. 22. Oh S, Goto S, Accetta G, et al. Vitamin K antagonist control in patients with atrial brillation in Asia compared with other regions of the world: Real-world data from the GARFIELD-AF registry. Int J Cardiol. 2016;223:543-547. 23. J-RHYTHM Registry Investigators. Determinants of warfarin use and international normalized ratio levels in atrial brillation patients in Japan. Subanalysis of the J-RHYTHM Registry. Circ J. 2011;75(10):2357-2362. 24. Akao M, Chun YH, Wada H, et al. Current status of clinical background of patients with atrial brillation in a community- based survey: the Fushimi AF Registry. J Cardiol. 2013;61(4):260- 266. 25. Guo Y, Apostolakis S, Blann AD, et al. Validation of contemporary stroke and bleeding risk strati cation scores in non-anticoagulated Chinese patients with atrial brillation. Int J Cardiol. 2013;168(2): 904-909. 26. Xia S-j, Du X, Li C, et al. Uptake of evidence-based statin therapy among atrial brillation patients in China: a report from the CAFR (Chinese Atrial Fibrillation Registry) Study. Int J Cardiol. 2016;220: 284-289. 27.


Uptake of evidence-based statin therapy among atrial brillation patients in China: a report from the CAFR (Chinese Atrial Fibrillation Registry) Study. Int J Cardiol. 2016;220: 284-289. 27. Huisman MV, Ma CS, Diener HC, et al. Antithrombotic therapy use in patients with atrial brillation before the era of non-vitamin K antagonist oral anticoagulants: the Global Registry on Long- Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation (GLORIA-AF) Phase I cohort. Europace. 2016;18(9): 1308-1318. 28. Chao TF, Liu CJ, Wang KL, et al. Using the CHA2DS2-VASc score for re ning stroke risk strati cation in low-risk Asian patients with atrial brillation. J Am Coll Cardiol. 2014;64(16):1658-1665. 29. Siu CW, Lip GY, Lam KF, Tse HF. Risk of stroke and intracranial hemorrhage in 9727 Chinese with atrial brillation in Hong Kong. Heart Rhythm. 2014;11(8):1401-1408. 30. Nieuwlaat R, Capucci A, Camm AJ, et al. Atrial brillation management: a prospective survey in ESC member countries. Eur Heart J. 2005;26(22):2422-2434. 31. Le Heuzey JY, Breithardt G, Camm J, et al. The RecordAF study: design, baseline data, and pro le of patients according to chosen treatment strategy for atrial brillation. Am J Cardiol. 2010;105(5): 687-693. 32. Steinberg BA, Holmes DN, Ezekowitz MD, et al. Rate versus rhythm control for management of atrial brillation in clinical practice: results from the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF) registry. Am Heart J. 2013;165(4):622-629. 33. Lip GYH, Laroche C, Dan GA, et al. A prospective survey in European Society of Cardiology member countries of atrial brillation management: baseline results of EURObservational Research Programme Atrial Fibrillation (EORP-AF) Pilot General Registry. Europace. 2014;16(3):308-319. 34. Kirchhof P, Ammentorp B, Darius H, et al.


2014;16(3):308-319. 34. Kirchhof P, Ammentorp B, Darius H, et al. Management of atrial brillation in seven European countries after the publication of the 2010 ESC Guidelines on atrial brillation: primary results of the PREvention oF thromboemolic events European Registry in Atrial Fibrillation (PREFER in AF). Europace. 2014;16(1):6-14. 35. Ha AC, Singh N, Cox JL, et al. Oral anticoagulation for stroke prevention in Canadian practice: Stroke Prevention and Rhythm Interventions in Atrial Fibrillation (SPRINT-AF) Registry. Can J Cardiol. 2016;32(2):204-210. 36. Zubaid M, Rashed WA, Alsheikh-Ali AA, et al. Gulf Survey of Atrial Fibrillation Events (Gulf SAFE): design and baseline characteristics of patients with atrial brillation in the Arab Middle East. Circ Cardiovasc Qual Outcomes. 2011;4(4):477-482. 37. Chiang C-E, Wu T-J, Ueng K-C, et al. 2016 Guidelines of the Taiwan Heart Rhythm Society and the Taiwan Society of Cardiology for the management of atrial brillation. J Formosan Medical Assoc. 2016;115(11):893-952. 38. Friberg L, Rosenqvist M, Lip GYH. Evaluation of risk strati cation schemes for ischaemic stroke and bleeding in 182 678 patients with atrial brillation: the Swedish Atrial Fibrillation cohort study. Eur Heart J. 2012;33(12):1500-1510. 39. Mareedu RK, Abdalrahman IB, Dharmashankar KC, et al. Atrial utter versus atrial brillation in a general population: differences in comorbidities associated with their respective onset. Clin Med Res. 2010;8(1):1-6. 40. Potpara TS, Lip GY. Lone atrial brillation an overview. Int J Clin Pract. 2014;68(4):418-433. 41. Granada J, Uribe W, Chyou PH, et al. Incidence and predictors of atrial utter in the general population. J Am Coll Cardiol. 2000;36(7):2242-2246. 42. Pisters R, Lane DA, Marin F, Camm AJ, Lip GY. Stroke and thromboembolism in atrial brillation. Circ J. 2012;76(10): 2289-2304. 43. Ganesan AN, Chew DP, Hartshorne T, et al.


2012;76(10): 2289-2304. 43. Ganesan AN, Chew DP, Hartshorne T, et al. The impact of atrial brillation type on the risk of thromboembolism, mortality, and bleeding: a systematic review and meta-analysis. Eur Heart J. 2016;37(20):1591-1602. 44. Wasywich CA, Pope AJ, Somaratne J, Poppe KK, Whalley GA, Doughty RN. Atrial brillation and the risk of death in patients with heart failure: a literature-based meta-analysis. Intern Med J. 2010;40(5):347-356. 45. Melgaard L, Gorst-Rasmussen A, Lane DA, Rasmussen LH, Larsen TB, Lip GY. Assessment of the CHA2DS2-VASc score in predicting ischemic stroke, thromboembolism, and death in patients with heart failure with and without atrial brillation. JAMA. 2015;314(10):1030-1038. 46. Ling LH, Kistler PM, Kalman JM, Schilling RJ, Hunter RJ. Comorbidity of atrial brillation and heart failure. Nat Rev Cardiol. 2016;13(3):131-147. 47. P ster R, Bragelmann J, Michels G, Wareham NJ, Luben R, Khaw KT. Performance of the CHARGE-AF risk model for incident atrial brillation in the EPIC Norfolk cohort. Eur J Prev Cardiol. 2015;22(7):932-939. 48. Kotecha D, Chudasama R, Lane DA, Kirchhof P, Lip GY. Atrial brillation and heart failure due to reduced versus preserved ejection fraction: a systematic review and meta-analysis of death and adverse outcomes. Int J Cardiol. 2016;203:660-666. 49. Zeng WT, Sun XT, Tang K, et al. Risk of thromboembolic events in atrial brillation with chronic kidney disease. Stroke. 2015;46(1): 157-163. 50. Olesen JB, Lip GY, Kamper AL, et al. Stroke and bleeding in atrial brillation with chronic kidney disease. N Engl J Med. 2012;367(7): 625-635. 51. Odutayo A, Wong CX, Hsiao AJ, Hopewell S, Altman DG, Emdin CA. Atrial brillation and risks of cardiovascular disease, renal disease, and death: systematic review and meta-analysis. BMJ. 2016;354:i4482. 52. Ando G, Capranzano P. Non-vitamin K antagonist oral anticoagulants in atrial brillation patients with chronic kidney disease: a systematic review and network meta-analysis.


Ando G, Capranzano P. Non-vitamin K antagonist oral anticoagulants in atrial brillation patients with chronic kidney disease: a systematic review and network meta-analysis. Int J Cardiol. 2017;231:162-169. 53. Dahal K, Kunwar S, Rijal J, Schulman P, Lee J. Stroke, major bleeding, and mortality outcomes in warfarin users with atrial brillation and chronic kidney disease: a meta-analysis of observational studies. Chest. 2016;149(4):951-959. 54. Li M, Liu T, Luo D, Li GP. Systematic review and meta- analysis of chronic kidney disease as predictor of atrial brillation recurrence following catheter ablation. Cardiol J. 2014;21(1):89-95. 55. Glotzer TV, Ziegler PD. Cryptogenic stroke: is silent atrial brillation the culprit? Heart Rhythm. 2015;12(1):234-241. 56. Korompoki E, Del Giudice A, Hillmann S, et al. Cardiac monitoring for detection of atrial brillation after TIA: a systematic review and meta-analysis. Int J Stroke. 2017;12(1):33-45. 57. Providencia R, Trigo J, Paiva L, Barra S. The role of echocardiography in thromboembolic risk assessment of patients with nonvalvular atrial brillation. J Am Soc Echocardiogr. 2013;26(8):801-812. 58. Zabalgoitia M, Halperin JL, Pearce LA, Blackshear JL, Asinger RW, Hart RG. Transesophageal echocardiographic correlates of clinical risk of thromboembolism in nonvalvular atrial brillation. Stroke Prevention in Atrial Fibrillation III Investigators. J Am Coll Cardiol. 1998;31(7):1622-1626. 59. Leung DY, Black IW, Cranney GB, Hopkins AP, Walsh WF. Prognostic implications of left atrial spontaneous echo contrast in nonvalvular atrial brillation. J Am Coll Cardiol. 1994;24(3):755- 762. 60. Calenda BW, Fuster V, Halperin JL, Granger CB. Stroke risk assessment in atrial brillation: risk factors and markers of atrial myopathy. Nat Rev Cardiol. 2016;13(9):549-559. 61. Quinn GR, Severdija ON, Chang Y, Singer DE. Wide variation in reported rates of stroke across cohorts of patients with atrial brillation. Circulation. 2017;135(3):208-219. 62. Nielsen PB, Lip GY. Adding rigor to stroke rate investigations in patients with atrial brillation. Circulation. 2017;135(3):220-223. 63.


Adding rigor to stroke rate investigations in patients with atrial brillation. Circulation. 2017;135(3):220-223. 63. Nielsen PB, Larsen TB, Skjoth F, Overvad TF, Lip GY. Stroke and thromboembolic event rates in atrial brillation according to different guideline treatment thresholds: a nationwide cohort study. Sci Rep. 2016;6:27410. 64. Chao TF, Wang KL, Liu CJ, et al. Age threshold for increased stroke risk among patients with atrial brillation: a nationwide cohort study from Taiwan. J Am Coll Cardiol. 2015;66(12):1339- 1347. 65. Chao TF, Lip GY, Liu CJ, et al. Validation of a modi ed CHA2DS2- VASc score for stroke risk strati cation in Asian patients with atrial brillation: a nationwide cohort study. Stroke. 2016;47(10):2462- 2469. 66. Nielsen PB, Skjoth F, Overvad TF, Larsen TB, Lip GYH. Female sex is a risk modi er rather than a risk factor for stroke in atrial brillation: should we use a CHA2DS2-VA score rather than CHA2DS2-VASc? Circulation. 2018;137(8):832-840. 67. Chao TF, Lip GYH, Liu CJ, et al. Relationship of aging and incident comorbidities to stroke risk in patients with atrial brillation. J Am Coll Cardiol. 2018;71(2):122-132. 68. Bousser MG, Bouthier J, Buller HR, et al. Comparison of idraparinux with vitamin K antagonists for prevention of thromboembolism in patients with atrial brillation: a randomised, open-label, non-inferiority trial. Lancet. 2008;371(9609):315-321. 69. Fang MC, Go AS, Chang Y, et al. A New risk scheme to predict warfarin-associated hemorrhage: the ATRIA (Anticoagulation and Risk Factors in Atrial Fibrillation) study. J Am Coll Cardiol. 2011;58(4):395-401. 70. Deitelzweig SB, Pinsky B, Buysman E, et al. Bleeding as an outcome among patients with nonvalvular atrial brillation in a large managed care population. Clin Ther. 2013;35(10):1536-1545.e1531. 71. Schulman S, Kearon C. De nition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. J Thromb Haemost. 2005;3(4):692-694. 72.


Schulman S, Kearon C. De nition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. J Thromb Haemost. 2005;3(4):692-694. 72. Connolly SJ, Ezekowitz MD, Yusuf S, et al. Dabigatran versus warfarin in patients with atrial brillation. N Engl J Med. 2009;361(12):1139-1151. 73. Patel MR, Mahaffey KW, Garg J, et al. Rivaroxaban versus warfarin in nonvalvular atrial brillation. N Engl J Med. 2011;365(10):883- 891. 74. Granger CB, Alexander JH, McMurray JJ, et al. Apixaban versus warfarin in patients with atrial brillation. N Engl J Med. 2011;365(11):981-992. 75. Hori M, Matsumoto M, Tanahashi N, et al. Rivaroxaban vs. warfarin in Japanese patients with atrial brillation the J-ROCKET AF study. Circ J. 2012;76(9):2104-2111. 76. Giugliano RP, Ruff CT, Braunwald E, et al. Edoxaban versus warfarin in patients with atrial brillation. N Engl J Med. 2013;369(22):2093-2104. 77. Chao TF, Lip GYH, Lin YJ, et al. Incident risk factors and major bleeding in patients with atrial brillation treated with oral anticoagulants: a comparison of baseline, follow-up and Delta HAS-BLED scores with an approach focused on modi able bleeding risk factors. Thromb Haemost. 2018;118(4):768-777. 78. Chao TF, Lip GYH, Lin YJ, et al. Major bleeding and intracranial hemorrhage risk prediction in patients with atrial brillation: attention to modi able bleeding risk factors or use of a bleeding risk strati cation score? A nationwide cohort study. Int J Cardiol. 2018;254:157-161. 79. Guo Y, Zhu H, Chen Y, Lip GYH. Comparing bleeding risk assessment focused on modi able risk factors only versus validated bleeding risk scores in atrial brillation. Am J Med. 2018;131(2): 185-192. 80. Esteve-Pastor MA, Rivera-Caravaca JM, Shantsila A, Roldan V, Lip GYH, Marin F. Assessing bleeding risk in atrial brillation patients: comparing a bleeding risk score based only on modi able bleeding risk factors against the HAS-BLED Score. The AMADEUS Trial.


Esteve-Pastor MA, Rivera-Caravaca JM, Shantsila A, Roldan V, Lip GYH, Marin F. Assessing bleeding risk in atrial brillation patients: comparing a bleeding risk score based only on modi able bleeding risk factors against the HAS-BLED Score. The AMADEUS Trial. Thromb Haemost. 2017;117(12):2261-2266. 81. Ageno W, Gallus AS, Wittkowsky A, Crowther M, Hylek EM, Palareti G. Oral anticoagulant therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(suppl 2):e44S-e88S. 82. Fang MC, Chang Y, Hylek EM, et al. Advanced age, anticoagulation intensity, and risk for intracranial hemorrhage among patients taking warfarin for atrial brillation. Ann Intern Med. 2004;141(10):745-752. 83. Hylek EM, Skates SJ, Sheehan MA, Singer DE. An analysis of the lowest effective intensity of prophylactic anticoagulation for patients with nonrheumatic atrial brillation. N Engl J Med. 1996;335(8):540-546. 84. Singer DE, Fang MC, Go AS. The international normalized ratio range of 2.0 to 3.0 remains appropriate for atrial brillation. Arch Intern Med. 2009;169(21):2032; author reply 2033. 85. Walker AM, Bennett D. Epidemiology and outcomes in patients with atrial brillation in the United States. Heart Rhythm. 2008;5(10):1365-1372. 86. Witt DM, Delate T, Hylek EM, et al. Effect of warfarin on intracranial hemorrhage incidence and fatal outcomes. Thrombosis Res. 2013;132(6):770-775. 87. Clarkesmith DE, Pattison HM, Lip GY, Lane DA. Educational intervention improves anticoagulation control in atrial brillation patients: the TREAT randomised trial. PloS One. 2013;8(9):e74037. 88. Levi M, de Peuter OR, Kamphuisen PW. Management strategies for optimal control of anticoagulation in patients with atrial brillation. Semin Thromb Hemost. 2009;35(6):560-567. 1190 Evidence-Based Medicine [ 1 5 4 # 5 C H E S T N O V E M B E R 2 0 1 8 ] 89. Matchar DB, Jacobson A, Dolor R, et al.


1190 Evidence-Based Medicine [ 1 5 4 # 5 C H E S T N O V E M B E R 2 0 1 8 ] 89. Matchar DB, Jacobson A, Dolor R, et al. Effect of home testing of international normalized ratio on clinical events. N Engl J Med. 2010;363(17):1608-1620. 90. van Walraven C, Jennings A, Oake N, Fergusson D, Forster AJ. Effect of study setting on anticoagulation control: a systematic review and metaregression. Chest. 2006;129(5):1155-1166. 91. Heneghan CJ, Garcia-Alamino JM, Spencer EA, et al. Self- monitoring and self-management of oral anticoagulation. Cochrane Database Syst Rev. 2016;7:CD003839. 92. Lip GY, Windecker S, Huber K, et al. Management of antithrombotic therapy in atrial brillation patients presenting with acute coronary syndrome and/or undergoing percutaneous coronary or valve interventions: a joint consensus document of the European Society of Cardiology Working Group on Thrombosis, European Heart Rhythm Association (EHRA), European Association of Percutaneous Cardiovascular Interventions (EAPCI) and European Association of Acute Cardiac Care (ACCA) endorsed by the Heart Rhythm Society (HRS) and Asia-Paci c Heart Rhythm Society (APHRS). Eur Heart J. 2014;35(45):3155-3179. 93. Douketis JD, Hasselblad V, Ortel TL. Bridging anticoagulation in patients with atrial brillation. N Engl J Med. 2016;374(1): 93-94. 94. Douketis JD, Spyropoulos AC, Kaatz S, et al. Perioperative bridging anticoagulation in patients with atrial brillation. N Engl J Med. 2015;373(9):823-833. 95. Man-Son-Hing M, Nichol G, Lau A, Laupacis A. Choosing antithrombotic therapy for elderly patients with atrial brillation who are at risk for falls. Arch Intern Med. 1999;159(7):677-685. 96. Pastori D, Lip GYH, Farcomeni A, et al. Incidence of bleeding in patients with atrial brillation and advanced liver brosis on treatment with vitamin K or non-vitamin K antagonist oral anticoagulants. Int J Cardiol. 2018;264:58-63. 97. Kuo L, Chao TF, Liu CJ, et al.


2018;264:58-63. 97. Kuo L, Chao TF, Liu CJ, et al. Liver cirrhosis in patients with atrial brillation: would oral anticoagulation have a net clinical bene t for stroke prevention? J Am Heart Assoc. 2017;6(6). 98. Pisters R, Lane DA, Nieuwlaat R, de Vos CB, Crijns HJ, Lip GY. A novel user-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in patients with atrial brillation: the Euro Heart Survey. Chest. 2010;138(5):1093-1100. 99. Gage BF, Yan Y, Milligan PE, et al. Clinical classi cation schemes for predicting hemorrhage: results from the National Registry of Atrial Fibrillation (NRAF). Am Heart J. 2006;151(3):713-719. 100. Hijazi Z, Oldgren J, Lindback J, et al. The novel biomarker-based ABC (age, biomarkers, clinical history)-bleeding risk score for patients with atrial brillation: a derivation and validation study. Lancet. 2016;387(10035):2302-2311. 101. O Brien EC, Simon DN, Thomas LE, et al. The ORBIT bleeding score: a simple bedside score to assess bleeding risk in atrial brillation. Eur Heart J. 2015;36(46):3258-3264. 102. Shireman TI, Mahnken JD, Howard PA, Kresowik TF, Hou Q, Ellerbeck EF. Development of a contemporary bleeding risk model for elderly warfarin recipients. Chest. 2006;130(5):1390-1396. 103. Zulki y HH, Lip GYH, Lane DA. Bleeding risk scores in atrial brillation and venous thromboembolism. Am J Cardiol. 2017;120(7):1139-1145. 104. Apostolakis S, Lane DA, Buller H, Lip GY. Comparison of the CHADS2, CHA2DS2-VASc and HAS-BLED scores for the prediction of clinically relevant bleeding in anticoagulated patients with atrial brillation: the AMADEUS trial. Thromb Haemost. 2013;110(5):1074-1079. 105. Roldan V, Marin F, Manzano-Fernandez S, et al. The HAS-BLED score has better prediction accuracy for major bleeding than CHADS2 or CHA2DS2-VASc scores in anticoagulated patients with atrial brillation. J Am Coll Cardiol. 2013;62(23):2199-2204. 106.


The HAS-BLED score has better prediction accuracy for major bleeding than CHADS2 or CHA2DS2-VASc scores in anticoagulated patients with atrial brillation. J Am Coll Cardiol. 2013;62(23):2199-2204. 106. Zhu W, He W, Guo L, Wang X, Hong K. The HAS-BLED score for predicting major bleeding risk in anticoagulated patients with atrial brillation: a systematic review and meta-analysis. Clin Cardiol. 2015;38(9):555-561. 107. Lip GY, Lane DA, Buller H, Apostolakis S. Development of a novel composite stroke and bleeding risk score in patients with atrial brillation: the AMADEUS Study. Chest. 2013;144(6):1839-1847. 108. Banerjee A, Fauchier L, Bernard-Brunet A, Clementy N, Lip GY. Composite risk scores and composite endpoints in the risk prediction of outcomes in anticoagulated patients with atrial brillation. The Loire Valley Atrial Fibrillation Project. Thromb Haemost. 2014;111(3):549-556. 109. Smith JG, Wieloch M, Koul S, et al. Triple antithrombotic therapy following an acute coronary syndrome: prevalence, outcomes and prognostic utility of the HAS-BLED score. EuroIntervention. 2012;8(6):672-678. 110. Thomas MR, Lip GY. Novel Risk Markers and Risk Assessments for Cardiovascular Disease. Circ Res. 2017;120(1):133-149. 111. Ban N, Siegfried CJ, Lin JB, et al. GDF15 is elevated in mice following retinal ganglion cell death and in glaucoma patients. JCI Insight. 2017;2(9). 112. Rivera-Caravaca JM, Roldan V, Esteve-Pastor MA, et al. Long-term stroke risk prediction in patients with atrial brillation: comparison of the ABC-Stroke and CHA2DS2-VASc scores. J Am Heart Assoc. 2017;6(7). 113. Esteve-Pastor MA, Rivera-Caravaca JM, Roldan V, et al. Long-term bleeding risk prediction in real world patients with atrial brillation: comparison of the HAS-BLED and ABC-Bleeding risk scores. The Murcia Atrial Fibrillation Project. Thromb Haemost. 2017;117(10):1848-1858. 114. Lip GY, Lane DA. Bleeding risk assessment in atrial brillation: observations on the use and misuse of bleeding risk scores. J Thromb Haemost. 2016;14(9):1711-1714. 115. Caldeira D, Costa J, Fernandes RM, Pinto FJ, Ferreira JJ.


Caldeira D, Costa J, Fernandes RM, Pinto FJ, Ferreira JJ. Performance of the HAS-BLED high bleeding-risk category, compared to ATRIA and HEMORR2HAGES in patients with atrial brillation: a systematic review and meta-analysis. J Interv Card Electrophysiol. 2014;40(3):277-284. 116. Apostolakis S, Lane DA, Guo Y, Buller H, Lip GY. Performance of the HEMORR 2 HAGES, ATRIA, and HAS-BLED bleeding risk- prediction scores in nonwarfarin anticoagulated atrial brillation patients. J Am Coll Cardiol. 2013;61(3):386-387. 117. Apostolakis S, Lane DA, Guo Y, Buller H, Lip GY. Performance of the HEMORR(2)HAGES, ATRIA, and HAS-BLED bleeding risk- prediction scores in patients with atrial brillation undergoing anticoagulation: the AMADEUS (evaluating the use of SR34006 compared to warfarin or acenocoumarol in patients with atrial brillation) study. J Am Coll Cardiol. 2012;60(9):861-867. 118. Senoo K, Proietti M, Lane DA, Lip GY. Evaluation of the HAS- BLED, ATRIA, and ORBIT bleeding risk scores in patients with atrial brillation taking warfarin. Am J Med. 2016;129(6):600-607. 119. Proietti M, Senoo K, Lane DA, Lip GY. Major bleeding in patients with non-valvular atrial brillation: impact of time in therapeutic range on contemporary bleeding risk scores. Sci Rep. 2016;6:24376. 120. Hart RG, Pearce LA, Aguilar MI. Meta-analysis: antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial brillation. Ann Intern Med. 2007;146(12):857-867. 121. Stroke Prevention in Atrial Fibrillation Study. Final results. Circulation. 1991;84(2):527-539. 122. Investigators A, Connolly SJ, Pogue J, et al. Effect of clopidogrel added to aspirin in patients with atrial brillation. N Engl J Med. 2009;360(20):2066-2078. 123. Investigators AWGotA, Connolly S, Pogue J, et al. Clopidogrel plus aspirin versus oral anticoagulation for atrial brillation in the Atrial brillation Clopidogrel Trial with Irbesartan for prevention of Vascular Events (ACTIVE W): a randomised controlled trial. Lancet. 2006;367(9526):1903-1912. 124. Ruff CT, Giugliano RP, Braunwald E, et al.


2006;367(9526):1903-1912. 124. Ruff CT, Giugliano RP, Braunwald E, et al. Comparison of the ef cacy and safety of new oral anticoagulants with warfarin in patients with atrial brillation: a meta-analysis of randomised trials. Lancet. 2014;383(9921):955-962. 125. Connolly SJ, Eikelboom J, Joyner C, et al. Apixaban in patients with atrial brillation. N Engl J Med. 2011;364(9):806-817. 126. Freedman B, Lip GY. Unreal world or real world data in oral anticoagulant treatment of atrial brillation. Thromb Haemost. 2016;116(4):587-589. 127. Carmo J, Moscoso Costa F, Ferreira J, Mendes M. Dabigatran in real-world atrial brillation. Meta-analysis of observational comparison studies with vitamin K antagonists. Thromb Haemost. 2016;116(4):754-763. 128. Bai Y, Deng H, Shantsila A, Lip GY. Rivaroxaban versus dabigatran or warfarin in real-world studies of stroke prevention in atrial brillation: systematic review and meta-analysis. Stroke. 2017;48(4): 970-976. 129. Larsen TB, Skjoth F, Nielsen PB, Kjaeldgaard JN, Lip GY. Comparative effectiveness and safety of non-vitamin K antagonist oral anticoagulants and warfarin in patients with atrial brillation: propensity weighted nationwide cohort study. BMJ. 2016;353:i3189. 130. Graham DJ, Reichman ME, Wernecke M, et al. Stroke, bleeding, and mortality risks in elderly Medicare bene ciaries treated with dabigatran or rivaroxaban for nonvalvular atrial brillation. JAMA Intern Med. 2016;176(11):1662-1671. 131. Shen AY, Yao JF, Brar SS, Jorgensen MB, Chen W. Racial/ethnic differences in the risk of intracranial hemorrhage among patients with atrial brillation. J Am Coll Cardiol. 2007;50(4):309-315. 132. Chiang CE, Wang KL, Lip GY. Stroke prevention in atrial brillation: an Asian perspective. Thromb Haemost. 2014;111(5): 789-797. 133. Lip GY, Wang KL, Chiang CE. Non-vitamin K antagonist oral anticoagulants (NOACs) for stroke prevention in Asian patients with atrial brillation: time for a reappraisal. Int J Cardiol. 2015;180:246-254. 134. Wang KL, Lip GY, Lin SJ, Chiang CE.


2015;180:246-254. 134. Wang KL, Lip GY, Lin SJ, Chiang CE. Non-vitamin K antagonist oral anticoagulants for stroke prevention in Asian patients with nonvalvular atrial brillation: meta-analysis. Stroke. 2015;46(9): 2555-2561. 135. Chan YH, Yen KC, See LC, et al. Cardiovascular, bleeding, and mortality risks of dabigatran in Asians with nonvalvular atrial brillation. Stroke. 2016;47(2):441-449. 136. Chan YH, Kuo CT, Yeh YH, et al. Thromboembolic, bleeding, and mortality risks of rivaroxaban and dabigatran in Asians with nonvalvular atrial brillation. J Am Coll Cardiol. 2016;68(13):1389- 1401. 137. Fredenburgh JC, Gross PL, Weitz JI. Emerging anticoagulant strategies. Blood. 2017;129(2):147-154. 138. van Montfoort ML, Meijers JC. Recent insights into the role of the contact pathway in thrombo-in ammatory disorders. Hematol Am Soc Hematol Educ Program. 2014;2014(1):60-65. 139. Gailani D. Future prospects for contact factors as therapeutic targets. Hematol Am Soc Hematol Educ Program. 2014;2014(1):52- 59. 140. Buller HR, Bethune C, Bhanot S, et al. Factor XI antisense oligonucleotide for prevention of venous thrombosis. N Engl J Med. 2015;372(3):232-240. 141. National Institutes of Health Clinical Center. NCT02553889. ClinicalTrials.gov. Bethesda, MD: National Institutes of Health. https://clinicaltrials.gov/ct2/show/NCT02553889. 142. Van de Werf F, Brueckmann M, Connolly SJ, et al. A comparison of dabigatran etexilate with warfarin in patients with mechanical heart valves: the randomized, phase II study to evaluate the safety and pharmacokinetics of oral dabigatran etexilate in patients after heart valve replacement (RE-ALIGN). Am Heart J. 2012;163(6): 931-937 e931. 143. 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(6):1087-1107. 144. Holbrook A, Schulman S, Witt DM, et al.


2013;110(6):1087-1107. 144. Holbrook A, Schulman S, Witt DM, et al. Evidence-based management of anticoagulant therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(suppl 2):e152S-e184S. 145. Hylek EM, Go AS, Chang Y, et al. Effect of intensity of oral anticoagulation on stroke severity and mortality in atrial brillation. N Engl J Med. 2003;349(11):1019-1026. 146. Hylek EM, Singer DE. Risk factors for intracranial hemorrhage in outpatients taking warfarin. Ann Intern Med. 1994;120(11):897- 902. 147. Oake N, Jennings A, Forster AJ, Fergusson D, Doucette S, van Walraven C. Anticoagulation intensity and outcomes among patients prescribed oral anticoagulant therapy: a systematic review and meta-analysis. CMAJ. 2008;179(3):235-244. 148. Hori M, Matsumoto M, Tanahashi N, et al. Safety and ef cacy of adjusted dose of rivaroxaban in Japanese patients with non-valvular atrial brillation: subanalysis of J-ROCKET AF for patients with moderate renal impairment. Circ J. 2013;77(3):632-638. 149. Yamaguchi T. Optimal intensity of warfarin therapy for secondary prevention of stroke in patients with nonvalvular atrial brillation: a multicenter, prospective, randomized trial. Japanese Nonvalvular Atrial Fibrillation-Embolism Secondary Prevention Cooperative Study Group. Stroke. 2000;31(4):817-821. 150. Rosendaal FR, Cannegieter SC, van der Meer FJ, Briet E. A method to determine the optimal intensity of oral anticoagulant therapy. Thromb Haemost. 1993;69(3):236-239. 151. Kaatz S. Determinants and measures of quality in oral anticoagulation therapy. J Thromb Thrombolysis. 2008;25(1):61-66. 152. Fitzmaurice DA, Accetta G, Haas S, et al. Comparison of international normalized ratio audit parameters in patients enrolled in GARFIELD-AF and treated with vitamin K antagonists. Br J Haematol. 2016;174(4):610-623. 153. Wan Y, Heneghan C, Perera R, et al. Anticoagulation control and prediction of adverse events in patients with atrial brillation: a systematic review. Circ Cardiovasc Qual Outcomes. 2008;1(2):84-91. 154.


Anticoagulation control and prediction of adverse events in patients with atrial brillation: a systematic review. Circ Cardiovasc Qual Outcomes. 2008;1(2):84-91. 154. Bjorck F, Renlund H, Lip GY, Wester P, Svensson PJ, Sjalander A. Outcomes in a warfarin-treated population with atrial brillation. JAMA Cardiol. 2016;1(2):172-180. 155. Haas S, Ten Cate H, Accetta G, et al. Quality of Vitamin K antagonist control and 1-year outcomes in patients with atrial brillation: a global perspective from the GARFIELD-AF registry. PloS One. 2016;11(10):e0164076. 156. Hylek EM. Vitamin K antagonists and time in the therapeutic range: implications, challenges, and strategies for improvement. J Thromb Thrombolysis. 2013;35(3):333-335. 157. Kirchhof P, Benussi S, Kotecha D, et al. 2016 ESC Guidelines for the management of atrial brillation developed in collaboration with EACTS. Eur Heart J. 2016;37(38):2893-2962. 158. National Clinical Guideline C. National Institute for Health and Clinical Excellence: Guidance. Atrial Fibrillation: The Management of Atrial Fibrillation. London, United Kingdom: National Institute for Health and Care Excellence. Copyright National Clinical Guideline Centre, 2014; 2014. 159. Massaro A, Giugliano RP, Norrving B, Oto A, Veltkamp R. Overcoming global challenges in stroke prophylaxis in atrial brillation: the role of non-vitamin K antagonist oral anticoagulants. Int J Stroke. 2016;11(9):950-967. 160. Rao SR, Reisman JI, Kressin NR, et al. Explaining racial disparities in anticoagulation control: results from a study of patients at the Veterans Administration. Am J Med Qual. 2015;30(3):214-222. 161. Rose AJ, Berlowitz DR, Miller DR, et al. INR targets and site-level anticoagulation control: results from the Veterans AffaiRs Study to Improve Anticoagulation (VARIA). J Thromb Haemost. 2012;10(4): 590-595. 162. Rose AJ, Hylek EM, Berlowitz DR, Ash AS, Reisman JI, Ozonoff A. Prompt repeat testing after out-of-range INR values: a quality indicator for anticoagulation care. Circ Cardiovasc Qual Outcomes. 2011;4(3):276-282. 163. Piccini JP, Hellkamp AS, Lokhnygina Y, et al.


2011;4(3):276-282. 163. Piccini JP, Hellkamp AS, Lokhnygina Y, et al. Relationship between time in therapeutic range and comparative treatment effect of rivaroxaban and warfarin: results from the ROCKET AF trial. J Am Heart Assoc. 2014;3(2):e000521. 1192 Evidence-Based Medicine [ 1 5 4 # 5 C H E S T N O V E M B E R 2 0 1 8 ] 164. Shimada YJ, Yamashita T, Koretsune Y, et al. Effects of regional differences in asia on ef cacy and safety of edoxaban compared with warfarin insights from the ENGAGE AF-TIMI 48 Trial. Circ J. 2015;79(12):2560-2567. 165. Van Spall HG, Wallentin L, Yusuf S, et al. Variation in warfarin dose adjustment practice is responsible for differences in the quality of anticoagulation control between centers and countries: an analysis of patients receiving warfarin in the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) trial. Circulation. 2012;126(19):2309-2316. 166. Wallentin L, Lopes RD, Hanna M, et al. Ef cacy and safety of apixaban compared with warfarin at different levels of predicted international normalized ratio control for stroke prevention in atrial brillation. Circulation. 2013;127(22):2166-2176. 167. Wallentin L, Yusuf S, Ezekowitz MD, et al. Ef cacy and safety of dabigatran compared with warfarin at different levels of international normalised ratio control for stroke prevention in atrial brillation: an analysis of the RE-LY trial. Lancet. 2010;376(9745):975-983. 168. Shore S, Ho PM, Lambert-Kerzner A, et al. Site-level variation in and practices associated with dabigatran adherence. JAMA. 2015;313(14):1443-1450. 169. Violi F, Lip GY, Pignatelli P, Pastori D. Interaction between dietary vitamin K intake and anticoagulation by vitamin K antagonists: is it really true?: A systematic review. Medicine. 2016;95(10):e2895. 170. Pastori D, Pignatelli P, Cribari F, et al. Time to therapeutic range (TtTR), anticoagulation control, and cardiovascular events in vitamin K antagonists-naive patients with atrial brillation.


Time to therapeutic range (TtTR), anticoagulation control, and cardiovascular events in vitamin K antagonists-naive patients with atrial brillation. Am Heart J. 2018;200:32-36. 171. Lip GYH, Al-Saady N, Jin J, et al. Anticoagulation control in warfarin-treated patients undergoing cardioversion of atrial brillation (from the Edoxaban Versus Enoxaparin-Warfarin in Patients Undergoing Cardioversion of Atrial Fibrillation Trial). Am J Cardiol. 2017;120(5):792-796. 172. Apostolakis S, Sullivan RM, Olshansky B, Lip GY. Factors affecting quality of anticoagulation control among patients with atrial brillation on warfarin: the SAMe-TT(2)R(2) score. Chest. 2013;144(5):1555-1563. 173. Zulki y H, Lip GYH, Lane DA. Use of the SAMe-TT2R2 score to predict anticoagulation control in atrial brillation and venous thromboembolism patients treated with vitamin K antagonists: a review. Heart Rhythm. 2018;15(4):615-623. 174. Bernaitis N, Ching CK, Chen L, et al. The Sex, Age, Medical History, Treatment, Tobacco Use, Race Risk (SAMe TT2R2) Score predicts warfarin control in a Singaporean population. J Stroke Cerebrovasc Dis. 2017;26(1):64-69. 175. Chan PH, Hai JJ, Chan EW, et al. Use of the SAMe-TT2R2 score to predict good anticoagulation control with warfarin in Chinese patients with atrial brillation: relationship to ischemic stroke incidence. PloS One. 2016;11(3):e0150674. 176. Demelo-Rodriguez P, Postigo-Esteban A, Garcia-Fernandez- Bravo I, et al. Evaluation of the SAMe-TT2R2 score to predict the quality of anticoagulation control in a cohort of patients with venous thromboembolism treated with vitamin K antagonists. Thrombosis Res. 2016;147:58-60. 177. Gallego P, Roldan V, Marin F, et al. SAMe-TT2R2 score, time in therapeutic range, and outcomes in anticoagulated patients with atrial brillation. Am J Med. 2014;127(11):1083-1088. 178. Gorzelak-Pabis P, Zyzak S, Krewko L, Broncel M. Assessment of the mean time in the therapeutic INR range and the SAME-TT2R2 score in patients with atrial brillation and cognitive impairment. Polskie Archiwum Medycyny Wewnetrznej. 2016;126(7-8):494-501. 179.


Gorzelak-Pabis P, Zyzak S, Krewko L, Broncel M. Assessment of the mean time in the therapeutic INR range and the SAME-TT2R2 score in patients with atrial brillation and cognitive impairment. Polskie Archiwum Medycyny Wewnetrznej. 2016;126(7-8):494-501. 179. Lip GY, Haguenoer K, Saint-Etienne C, Fauchier L. Relationship of the SAMe-TT(2)R(2) score to poor-quality anticoagulation, stroke, clinically relevant bleeding, and mortality in patients with atrial brillation. Chest. 2014;146(3):719-726. 180. Lobos-Bejarano JM, Barrios V, Polo-Garcia J, et al. Evaluation of SAMe-TT2R2 score and other clinical factors in uencing the quality of anticoagulation therapy in non-valvular atrial brillation: a nationwide study in Spain. Current Medical Research And Opinion. 2016;32(7):1201-1207. 181. Poli D, Antonucci E, Testa S, Lip GY. A prospective validation of the SAME-TT2R 2 score: how to identify atrial brillation patients who will have good anticoagulation control on warfarin. Intern Emerg Med. 2014;9(4):443-447. 182. Roldan V, Cancio S, Galvez J, et al. The SAMe-TT2R2 score predicts poor anticoagulation control in AF patients: a prospective real-world inception cohort study. Am J Med. 2015;128(11):1237- 1243. 183. Ruiz-Ortiz M, Bertomeu V, Cequier A, Marin F, Anguita M. Validation of the SAMe-TT2R2 score in a nationwide population of nonvalvular atrial brillation patients on vitamin K antagonists. Thromb Haemost. 2015;114(4):695-701. 184. Skov J, Bladbjerg EM, Bor MV, Gram J. SAMeTT(2)R(2) does not predict time in therapeutic range of the international normalized ratio in patients attending a high-quality anticoagulation clinic. Chest. 2014;145(1):187-188. 185. Szymanski FM, Lip GY, Filipiak KJ, Platek AE, Karpinski G. Usefulness of the SAME-TT2R2 score to predict anticoagulation control on VKA in patients with atrial brillation and obstructive sleep apnea. Int J Cardiol. 2016;204:200-205. 186. Abumuaileq RR, Abu-Assi E, Raposeiras-Roubin S, et al.


2016;204:200-205. 186. Abumuaileq RR, Abu-Assi E, Raposeiras-Roubin S, et al. Evaluation of SAMe-TT2R2 risk score for predicting the quality of anticoagulation control in a real-world cohort of patients with non- valvular atrial brillation on vitamin-K antagonists. Europace. 2015;17(5):711-717. 187. Kataruka A, Kong X, Haymart B, et al. SAMe-TT2R2 predicts quality of anticoagulation in patients with acute venous thromboembolism: The MAQI2 experience. Vasc Med. 2017;22(3): 197-203. 188. Palareti G, Antonucci E, Lip GY, et al. The SAME-TT2R2 score predicts the quality of anticoagulation control in patients with acute VTE. A real-life inception cohort study. Thromb Haemost. 2016;115(6):1101-1108. 189. Barnes GD, Lucas E, Alexander GC, Goldberger ZD. National trends in ambulatory oral anticoagulant use. Am J Med. 2015;128(12):1300-1305.e1302. 190. Christensen TD, Larsen TB. Precision and accuracy of point-of- care testing coagulometers used for self-testing and self- management of oral anticoagulation therapy. J Thromb Haemost. 2012;10(2):251-260. 191. FDA. Food and Drug Administration. Point of Care PT/INR Devices for Monitoring Warfarin Therapy. https://www.fda.gov/ downloads/MedicalDevices/NewsEvents/WorkshopsConferences/ UCM491546.pdf. Accessed March 12, 2017. 192. Hohnloser SH, Hijazi Z, Thomas L, et al. Ef cacy of apixaban when compared with warfarin in relation to renal function in patients with atrial brillation: insights from the ARISTOTLE trial. Eur Heart J. 2012;33(22):2821-2830. 193. Hohnloser SH, Basic E, Nabauer M. Comparative risk of major bleeding with new oral anticoagulants (NOACs) and phenprocoumon in patients with atrial brillation: a post- marketing surveillance study. Clin Res Cardiol. 2017;106(8): 618-628. 194. Bytzer P, Connolly SJ, Yang S, et al. Analysis of upper gastrointestinal adverse events among patients given dabigatran in the RE-LY trial. Clin Gastroenterol Hepatol. 2013;11(3):246-252. e241-245. 195. Chan PH, Hai JJ, Huang D, et al. Burden of upper gastrointestinal symptoms in patients prescribed dabigatran for stroke prevention. SAGE Open Med. 2016;4:2050312116662414. 196. Ho MH, Ho CW, Cheung E, et al.


2016;4:2050312116662414. 196. Ho MH, Ho CW, Cheung E, et al. Continuation of dabigatran therapy in "real-world" practice in Hong Kong. PloS One. 2014;9(8): e101245. 197. Li XS, Deitelzweig S, Keshishian A, et al. Effectiveness and safety of apixaban versus warfarin in non-valvular atrial brillation patients in "real-world" clinical practice. A propensity-matched analysis of 76,940 patients. Thromb Haemost. 2017;117(6):1072-1082. 198. Bai Y, Shi XB, Ma CS, Lip GYH. Meta-Analysis of Effectiveness and Safety of Oral Anticoagulants in Atrial Fibrillation With Focus on Apixaban. Am J Cardiol. 2017;120(9):1689-1695. 199. Vrijens B, Heidbuchel H. Non-vitamin K antagonist oral anticoagulants: considerations on once- vs. twice-daily regimens and their potential impact on medication adherence. Europace. 2015;17(4):514-523. 200. Wang KL, Chiu CC, Su-Yin Tan D, et al. Once- or twice-daily non- vitamin K antagonist oral anticoagulants in Asian patients with atrial brillation: a meta-analysis of randomized controlled trials. J Formos Med Assoc. 2017;116(8):591-598. 201. Chan PH, Huang D, Hai JJ, et al. Stroke prevention using dabigatran in elderly Chinese patients with atrial brillation. Heart Rhythm. 2016;13(2):366-373. 202. Angiolillo DJ, Goodman SG, Bhatt DL, et al. Antithrombotic therapy in patients with atrial brillation undergoing percutaneous coronary intervention: a North American Perspective-2016 Update. Circ Cardiovasc Interv. 2016;9(11). 203. Lane DA, Aguinaga L, Blomstrom-Lundqvist C, et al. Cardiac tachyarrhythmias and patient values and preferences for their management: the European Heart Rhythm Association (EHRA) consensus document endorsed by the Heart Rhythm Society (HRS), Asia Paci c Heart Rhythm Society (APHRS), and Sociedad Latinoamericana de Estimulacion Cardiaca y Electro siologia (SOLEACE). Europace. 2015;17(12):1747-1769. 204. Ruff CT, Giugliano RP, Antman EM. Management of bleeding with non-vitamin K antagonist oral anticoagulants in the era of speci c reversal agents. Circulation. 2016;134(3):248-261. 205. Heidbuchel H, Verhamme P, Alings M, et al.


2016;134(3):248-261. 205. Heidbuchel H, Verhamme P, Alings M, et al. Updated European Heart Rhythm Association Practical Guide on the use of non- vitamin K antagonist anticoagulants in patients with non-valvular atrial brillation. Europace. 2015;17(10):1467-1507. 206. Kovacs RJ, Flaker GC, Saxonhouse SJ, et al. Practical management of anticoagulation in patients with atrial brillation. J Am Coll Cardiol. 2015;65(13):1340-1360. 207. Weitz JI, Pollack CV Jr. Practical management of bleeding in patients receiving non-vitamin K antagonist oral anticoagulants. Thromb Haemost. 2015;114(6):1113-1126. 208. Aronis KN, Hylek EM. Who, when, and how to reverse non- vitamin K oral anticoagulants. J Thromb Thrombolysis. 2016;41(2): 253-272. 209. Wang X, Mondal S, Wang J, et al. Effect of activated charcoal on apixaban pharmacokinetics in healthy subjects. Am J Cardiovasc Drugs. 2014;14(2):147-154. 210. Woo JS, Kapadia N, Phanco SE, Lynch CA. Positive outcome after intentional overdose of dabigatran. J Med Toxicol. 2013;9(2):192- 195. 211. Sajkov D, Gallus A. Accidental rivaroxaban overdose in a patient with pulmonary embolism: some lessons for managing new oral anticoagulants. Clin Med Insights Case Rep. 2015;8:57-59. 212. van Ryn J, Stangier J, Haertter S, et al. Dabigatran etexilate a novel, reversible, oral direct thrombin inhibitor: interpretation of coagulation assays and reversal of anticoagulant activity. Thromb Haemost. 2010;103(6):1116-1127. 213. Pragst I, Zeitler SH, Doerr B, et al. Reversal of dabigatran anticoagulation by prothrombin complex concentrate (Beriplex P/N) in a rabbit model. J Thromb Haemost. 2012;10(9):1841-1848. 214. Godier A, Miclot A, Le Bonniec B, et al. Evaluation of prothrombin complex concentrate and recombinant activated factor VII to reverse rivaroxaban in a rabbit model. Anesthesiology. 2012;116(1): 94-102. 215. Lambourne MD, Eltringham-Smith LJ, Gataiance S, Arnold DM, Crowther MA, Shef eld WP. Prothrombin complex concentrates reduce blood loss in murine coagulopathy induced by warfarin, but not in that induced by dabigatran etexilate. J Thromb Haemost. 2012;10(9):1830-1840. 216.


Prothrombin complex concentrates reduce blood loss in murine coagulopathy induced by warfarin, but not in that induced by dabigatran etexilate. J Thromb Haemost. 2012;10(9):1830-1840. 216. Perzborn E, Gruber A, Tinel H, et al. Reversal of rivaroxaban anticoagulation by haemostatic agents in rats and primates. Thromb Haemost. 2013;110(1):162-172. 217. Martin AC, Le Bonniec B, Fischer AM, et al. Evaluation of recombinant activated factor VII, prothrombin complex concentrate, and brinogen concentrate to reverse apixaban in a rabbit model of bleeding and thrombosis. Int J Cardiol. 2013;168(4):4228-4233. 218. Zhou W, Zorn M, Nawroth P, et al. Hemostatic therapy in experimental intracerebral hemorrhage associated with rivaroxaban. Stroke. 2013;44(3):771-778. 219. Honickel M, Treutler S, van Ryn J, Tillmann S, Rossaint R, Grottke O. Reversal of dabigatran anticoagulation ex vivo: Porcine study comparing prothrombin complex concentrates and idarucizumab. Thromb Haemost. 2015;113(4):728-740. 220. Eerenberg ES, Kamphuisen PW, Sijpkens MK, Meijers JC, Buller HR, Levi M. Reversal of rivaroxaban and dabigatran by prothrombin complex concentrate: a randomized, placebo- controlled, crossover study in healthy subjects. Circulation. 2011;124(14):1573-1579. 221. Levi M, Moore KT, Castillejos CF, et al. Comparison of three- factor and four-factor prothrombin complex concentrates regarding reversal of the anticoagulant effects of rivaroxaban in healthy volunteers. J Thromb Haemost. 2014;12(9):1428- 1436. 222. Zahir H, Brown KS, Vandell AG, et al. Edoxaban effects on bleeding following punch biopsy and reversal by a 4-factor prothrombin complex concentrate. Circulation. 2015;131(1):82-90. 223. Baudo F, Collins P, Huth-Kuhne A, et al. Management of bleeding in acquired hemophilia A: results from the European Acquired Haemophilia (EACH2) Registry. Blood. 2012;120(1):39-46. 224. Dentali F, Marchesi C, Giorgi Pierfranceschi M, et al. Safety of prothrombin complex concentrates for rapid anticoagulation reversal of vitamin K antagonists. A meta-analysis. Thromb Haemost. 2011;106(3):429-438. 225. Ehrlich HJ, Henzl MJ, Gomperts ED.


Thromb Haemost. 2011;106(3):429-438. 225. Ehrlich HJ, Henzl MJ, Gomperts ED. Safety of factor VIII inhibitor bypass activity (FEIBA): 10-year compilation of thrombotic adverse events. Haemophilia. 2002;8(2):83-90. 226. Schiele F, van Ryn J, Canada K, et al. A speci c antidote for dabigatran: functional and structural characterization. Blood. 2013;121(18):3554-3562. 227. Eikelboom JW, Quinlan DJ, van Ryn J, Weitz JI. Idarucizumab: the antidote for reversal of dabigatran. Circulation. 2015;132(25):2412- 2422. 228. Pollack CV Jr, Reilly PA, van Ryn J, et al. Idarucizumab for dabigatran reversal full cohort analysis. N Engl J Med. 2017;377(5):431-441. 229. Lu G, DeGuzman FR, Hollenbach SJ, et al. A speci c antidote for reversal of anticoagulation by direct and indirect inhibitors of coagulation factor Xa. Nature medicine. 2013;19(4):446-451. 230. National Institutes of Health Clinical Center. NCT02329327. ClinicalTrials.gov. Bethesda, MD: National Institutes of Health. http://clinicaltrials.gov/ct2/show/NCT02329327. 231. Connolly SJ, Milling TJ Jr, Eikelboom JW, et al. Andexanet Alfa for Acute Major Bleeding Associated with Factor Xa Inhibitors. N Engl J Med. 2016;375(12):1131-1141. 232. Laulicht B, Bakhru S, Jiang X. Antidote for new oral anticoagulants: mechanism of action and binding speci city of PER977. J Thromb Haemost. 2013;11:75. 233. Moreyra E, Finkelhor RS, Cebul RD. Limitations of transesophageal echocardiography in the risk assessment of patients before nonanticoagulated cardioversion from atrial brillation and utter: an analysis of pooled trials. Am Heart J. 1995;129(1):71-75. 234. Gallagher MM, Hennessy BJ, Edvardsson N, et al. Embolic complications of direct current cardioversion of atrial arrhythmias: association with low intensity of anticoagulation at the time of cardioversion. J Am Coll Cardiol. 2002;40(5):926-933. 235. Berger M, Schweitzer P. Timing of thromboembolic events after electrical cardioversion of atrial brillation or utter: a retrospective analysis. Am J Cardiol. 1998;82(12):1545-1547. a1548. 236. Manning WJ, Leeman DE, Gotch PJ, Come PC.


1998;82(12):1545-1547. a1548. 236. Manning WJ, Leeman DE, Gotch PJ, Come PC. Pulsed Doppler evaluation of atrial mechanical function after electrical 1194 Evidence-Based Medicine [ 1 5 4 # 5 C H E S T N O V E M B E R 2 0 1 8 ] cardioversion of atrial brillation. J Am Coll Cardiol. 1989;13(3): 617-623. 237. Palomaki A, Mustonen P, Hartikainen JE, et al. Strokes after cardioversion of atrial brillation The FibStroke study. Int J Cardiol. 2016;203:269-273. 238. Sj lander S, Holmqvist F, Smith JG, et al. Assessment of use vs discontinuation of oral anticoagulation after pulmonary vein isolation in patients with atrial brillation. JAMA Cardiol. 2017;2(2):146-152. 239. Renda G, Ricci F, Giugliano RP, De Caterina R. Non-vitamin K antagonist oral anticoagulants in patients with atrial brillation and valvular heart disease. J Am Coll Cardiol. 2017;69(11):1363-1371. 240. Larsen TB, Potpara T, Dagres N, et al. Preference for oral anticoagulation therapy for patients with atrial brillation in Europe in different clinical situations: results of the European Heart Rhythm Association Survey. Europace. 2015;17(5):819-824. 241. Maan A, Heist EK, Ruskin JN, Mansour M. Practical issues in the management of novel oral anticoagulants-cardioversion and ablation. Journal of thoracic disease. 2015;7(2):115-131. 242. Cappato R, Ezekowitz MD, Klein AL, et al. Rivaroxaban vs. vitamin K antagonists for cardioversion in atrial brillation. Eur Heart J. 2014;35(47):3346-3355. 243. Xarelto. Summary of Product Characteristics. 2015; http://www. ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_ December 5, 2016. 244. Pradaxa. Summary of Product Characteristics. 2015; http://www. ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_ 2016. 245. Nielsen PB, Lane DA, Rasmussen LH, Lip GY, Larsen TB. Renal function and non-vitamin K oral anticoagulants in comparison with warfarin on safety and ef cacy outcomes in atrial brillation patients: a systemic review and meta-regression analysis. Clin Res Cardiol. 2015;104(5):418-429. 246. Chan PH, Huang D, Yip PS, et al.


2015;104(5):418-429. 246. Chan PH, Huang D, Yip PS, et al. Ischaemic stroke in patients with atrial brillation with chronic kidney disease undergoing peritoneal dialysis. Europace. 2016;18(5):665-671. 247. Ezekowitz MD, Pollack CV, Sanders P, et al. Apixaban compared with parenteral heparin and/or vitamin K antagonist in patients with nonvalvular atrial brillation undergoing cardioversion: rationale and design of the EMANATE trial. Am Heart J. 2016;179: 59-68. 248. Manning WJ, Silverman DI, Gordon SP, Krumholz HM, Douglas PS. Cardioversion from atrial brillation without prolonged anticoagulation with use of transesophageal echocardiography to exclude the presence of atrial thrombi. N Engl J Med. 1993;328(11):750-755. 249. Klein AL, Grimm RA, Murray RD, et al. Use of transesophageal echocardiography to guide cardioversion in patients with atrial brillation. N Engl J Med. 2001;344(19):1411-1420. 250. Caldeira D, Costa J, Ferreira JJ, Lip GY, Pinto FJ. Non-vitamin K antagonist oral anticoagulants in the cardioversion of patients with atrial brillation: systematic review and meta-analysis. Clin Res Cardiol. 2015;104(7):582-590. 251. Hoppensteadt D, Fareed J, Klein AL, et al. Comparison of anticoagulant and anti-in ammatory responses using enoxaparin versus unfractionated heparin for transesophageal echocardiography-guided cardioversion of atrial brillation. Am J Cardiol. 2008;102(7):842-846. 252. Klein AL, Jasper SE, Katz WE, et al. The use of enoxaparin compared with unfractionated heparin for short-term antithrombotic therapy in atrial brillation patients undergoing transoesophageal echocardiography-guided cardioversion: Assessment of Cardioversion Using Transoesophageal Echocardiography (ACUTE) II randomized multicentre study. Eur Heart J. 2006;27(23):2858-2865. 253. de Luca I, Sorino M, De Luca L, Colonna P, Del Salvatore B, Corliano L. Pre- and post-cardioversion transesophageal echocardiography for brief anticoagulation therapy with enoxaparin in atrial brillation patients: a prospective study with a 1-year follow-up. Int J Cardiol. 2005;102(3):447-454. 254. Wu LA, Chandrasekaran K, Friedman PA, et al. Safety of expedited anticoagulation in patients undergoing transesophageal echocardiographic-guided cardioversion. Am J Med. 2006;119(2): 142-146. 255.


Safety of expedited anticoagulation in patients undergoing transesophageal echocardiographic-guided cardioversion. Am J Med. 2006;119(2): 142-146. 255. Stellbrink C, Nixdorff U, Hofmann T, et al. Safety and ef cacy of enoxaparin compared with unfractionated heparin and oral anticoagulants for prevention of thromboembolic complications in cardioversion of nonvalvular atrial brillation: the Anticoagulation in Cardioversion using Enoxaparin (ACE) trial. Circulation. 2004;109(8):997-1003. 256. Di Minno MN, Ambrosino P, Dello Russo A, Casella M, Tremoli E, Tondo C. Prevalence of left atrial thrombus in patients with non- valvular atrial brillation. A systematic review and meta-analysis of the literature. Thromb Haemost. 2016;115(3):663-677. 257. Di Biase L, Briceno DF, Trivedi C, et al. Is transesophageal echocardiogram mandatory in patients undergoing ablation of atrial brillation with uninterrupted novel oral anticoagulants? Results from a prospective multicenter registry. Heart Rhythm. 2016;13(6):1197-1202. 258. Antonielli E, Pizzuti A, Palinkas A, et al. Clinical value of left atrial appendage ow for prediction of long-term sinus rhythm maintenance in patients with nonvalvular atrial brillation. J Am Coll Cardiol. 2002;39(9):1443-1449. 259. Berry C, Stewart S, Payne EM, McArthur JD, McMurray JJ. Electrical cardioversion for atrial brillation: outcomes in "real-life" clinical practice. Int J Cardiol. 2001;81(1):29-35. 260. Arnar DO, Danielsen R. Factors predicting maintenance of sinus rhythm after direct current cardioversion of atrial brillation and utter: a reanalysis with recently acquired data. Cardiology. 1996;87(3):181-188. 261. Paraskevaidis IA, Dodouras T, Tsiapras D, Kremastinos DT. Prediction of successful cardioversion and maintenance of sinus rhythm in patients with lone atrial brillation. Chest. 2005;127(2): 488-494. 262. Sherman DG, Kim SG, Boop BS, et al. Occurrence and characteristics of stroke events in the Atrial Fibrillation Follow-up Investigation of Sinus Rhythm Management (AFFIRM) study. Arch Intern Med. 2005;165(10):1185-1191. 263. Page RL, Wilkinson WE, Clair WK, McCarthy EA, Pritchett EL. Asymptomatic arrhythmias in patients with symptomatic paroxysmal atrial brillation and paroxysmal supraventricular tachycardia.


Asymptomatic arrhythmias in patients with symptomatic paroxysmal atrial brillation and paroxysmal supraventricular tachycardia. Circulation. 1994;89(1):224-227. 264. Stoddard MF, Dawkins PR, Prince CR, Ammash NM. Left atrial appendage thrombus is not uncommon in patients with acute atrial brillation and a recent embolic event: a transesophageal echocardiographic study. J Am Coll Cardiol. 1995;25(2):452-459. 265. Kleemann T, Becker T, Strauss M, Schneider S, Seidl K. Prevalence of left atrial thrombus and dense spontaneous echo contrast in patients with short-term atrial brillation < 48 hours undergoing cardioversion: value of transesophageal echocardiography to guide cardioversion. J Am Soc Echocardiogr. 2009;22(12):1403-1408. 266. Flaker GC, Belew K, Beckman K, et al. Asymptomatic atrial brillation: demographic features and prognostic information from the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) study. Am Heart J. 2005;149(4):657-663. 267. Airaksinen KE, Gronberg T, Nuotio I, et al. Thromboembolic complications after cardioversion of acute atrial brillation: the FinCV (Finnish CardioVersion) study. J Am Coll Cardiol. 2013;62(13):1187-1192. 268. Weigner MJ, Caul eld TA, Danias PG, Silverman DI, Manning WJ. Risk for clinical thromboembolism associated with conversion to sinus rhythm in patients with atrial brillation lasting less than 48 hours. Ann Intern Med. 1997;126(8):615-620. 269. Michael JA, Stiell IG, Agarwal S, Mandavia DP. Cardioversion of paroxysmal atrial brillation in the emergency department. Ann Emerg Med. 1999;33(4):379-387. 270. Burton JH, Vinson DR, Drummond K, Strout TD, Thode HC, McInturff JJ. Electrical cardioversion of emergency department patients with atrial brillation. Ann Emerg Med. 2004;44(1):20-30. 271. Stiell IG, Clement CM, Perry JJ, et al. Association of the Ottawa Aggressive Protocol with rapid discharge of emergency department patients with recent-onset atrial brillation or utter. CJEM. 2010;12(3):181-191. 272. Xavier Scheuermeyer F, Grafstein E, Stenstrom R, Innes G, Poureslami I, Sighary M. Thirty-day outcomes of emergency department patients undergoing electrical cardioversion for atrial brillation or utter. Acad Emerg Med. 2010;17(4):408-415.


Xavier Scheuermeyer F, Grafstein E, Stenstrom R, Innes G, Poureslami I, Sighary M. Thirty-day outcomes of emergency department patients undergoing electrical cardioversion for atrial brillation or utter. Acad Emerg Med. 2010;17(4):408-415. 273. Jaakkola S, Lip GY, Biancari F, et al. Predicting Unsuccessful Electrical Cardioversion for Acute Atrial Fibrillation (from the AF- CVS Score). Am J Cardiol. 2016. 274. Arnold AZ, Mick MJ, Mazurek RP, Loop FD, Trohman RG. Role of prophylactic anticoagulation for direct current cardioversion in patients with atrial brillation or atrial utter. J Am Coll Cardiol. 1992;19(4):851-855. 275. Chalasani P, Cambre S, Silverman ME. Direct-current cardioversion for the conversion of atrial utter. Am J Cardiol. 1996;77(8):658-660. 276. Basili S, Loffredo L, Pastori D, et al. Carotid plaque detection improves the predictive value of CHA2DS2-VASc score in patients with non-valvular atrial brillation: the ARAPACIS Study. Int J Cardiol. 2017;231:143-149. 277. Lip GYH, Collet JP, Haude M, et al. 2018 Joint European consensus document on the management of antithrombotic therapy in atrial brillation patients presenting with acute coronary syndrome and/ or undergoing percutaneous cardiovascular interventions: A joint consensus document of the European Heart Rhythm Association (EHRA), European Society of Cardiology Working Group on Thrombosis, European Association of Percutaneous Cardiovascular Interventions (EAPCI) and European Association of Acute Cardiac Care (ACCA) endorsed by the Heart Rhythm Society (HRS), Asia- Paci c Heart Rhythm Society (APHRS), Latin America Heart Rhythm Society (LAHRS) and Cardiac Arrhythmia Society of Southern Africa (CASSA) [published online ahead of print July 21, 2018]. Europace. https://doi.org/10.1093/europace/euy174. 278. Bonaca MP, Goto S, Bhatt DL, et al. Prevention of stroke with ticagrelor in patients with prior myocardial infarction: insights from PEGASUS-TIMI 54 (Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin-Thrombolysis in Myocardial Infarction 54). (1524-4539 (Electronic)). 279.


Prevention of stroke with ticagrelor in patients with prior myocardial infarction: insights from PEGASUS-TIMI 54 (Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin-Thrombolysis in Myocardial Infarction 54). (1524-4539 (Electronic)). 279. Proietti M, Airaksinen KEJ, Rubboli A, et al. Time in therapeutic range and major adverse outcomes in atrial brillation patients undergoing percutaneous coronary intervention: the Atrial Fibrillation Undergoing Coronary Artery Stenting (AFCAS) registry. Am Heart J. 2017;190:86-93. 280. Chaudhary N, Bundhun PK, Yan H. Comparing the clinical outcomes in patients with atrial brillation receiving dual antiplatelet therapy and patients receiving an addition of an anticoagulant after coronary stent implantation: a systematic review and meta-analysis of observational studies. Medicine (Baltimore). 2016;95(50):e5581. 281. Zhu W, Guo L, Liu F, et al. Ef cacy and safety of triple versus dual antithrombotic therapy in atrial brillation and ischemic heart disease: a systematic review and meta-analysis. Oncotarget. 2017;8(46):81154-81166. 282. Bennaghmouch N, de Veer AJWM, Bode K, et al. Ef cacy and safety of the use of non-vitamin K antagonist oral anticoagulants in patients with nonvalvular atrial brillation and concomitant aspirin therapy: a meta-analysis of randomized trials. Circulation. 2018;137(11):1117-1129. 283. Lamberts M, Gislason GH, Olesen JB, et al. Oral anticoagulation and antiplatelets in atrial brillation patients after myocardial infarction and coronary intervention. J Am Coll Cardiol. 2013;62(11):981-989. 284. Dewilde WJ, Oirbans T, Verheugt FW, 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(9872): 1107-1115. 285. Fiedler KA, Maeng M, Mehilli J, et al. Duration of triple therapy in patients requiring oral anticoagulation after drug-eluting stent implantation: the ISAR-TRIPLE Trial. J Am Coll Cardiol. 2015;65(16):1619-1629. 286. Gibson CM, Mehran R, Bode C, et al.


2015;65(16):1619-1629. 286. Gibson CM, Mehran R, Bode C, et al. Prevention of bleeding in patients with atrial brillation undergoing PCI. N Engl J Med. 2016;375(25):2423-2434. 287. Gibson CM, Pinto DS, Chi G, et al. Recurrent hospitalization among patients with atrial brillation undergoing intracoronary stenting treated with 2 treatment strategies of rivaroxaban or a dose-adjusted oral vitamin K antagonist treatment strategy. Circulation. 2017;135(4):323-333. 288. Cannon CP, Bhatt DL, Oldgren J, et al. Dual antithrombotic therapy with dabigatran after PCI in atrial brillation. N Engl J Med. 2017;377(16):1513-1524. 289. Sarafoff N, Martischnig A, Wealer J, et al. Triple therapy with aspirin, prasugrel, and vitamin K antagonists in patients with drug- eluting stent implantation and an indication for oral anticoagulation. J Am Coll Cardiol. 2013;61(20):2060-2066. 290. Ohman EM, Roe MT, Steg PG, et al. Clinically signi cant bleeding with low-dose rivaroxaban versus aspirin, in addition to P2Y12 inhibition, in acute coronary syndromes (GEMINI-ACS-1): a double-blind, multicentre, randomised trial. Lancet. 2017. 291. Nielsen PB, Skjoth F, Rasmussen LH, Larsen TB, Lip GY. Using the CHA2DS2-VASc score for stroke prevention in atrial brillation: a focus on vascular disease, women, and simple practical application. Can J Cardiol. 2015;31(6):820.e9-820.e10. 292. Lin LY, Lee CH, Yu CC, et al. Risk factors and incidence of ischemic stroke in Taiwanese with nonvalvular atrial brillation a nation wide database analysis. Atherosclerosis. 2011;217(1):292-295. 293. Lamberts M, Gislason GH, Lip GY, et al. Antiplatelet therapy for stable coronary artery disease in atrial brillation patients taking an oral anticoagulant: a nationwide cohort study. Circulation. 2014;129(15):1577-1585. 294. Kumar S, Danik SB, Altman RK, et al. Non-vitamin K antagonist oral anticoagulants and antiplatelet therapy for stroke prevention in patients with atrial brillation: a meta-analysis of randomized controlled trials. Cardiol Rev. 2016;24(5):218-223. 295. Dans AL, Connolly SJ, Wallentin L, et al.


2016;24(5):218-223. 295. Dans AL, Connolly SJ, Wallentin L, et al. Concomitant use of antiplatelet therapy with dabigatran or warfarin in the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) trial. Circulation. 2013;127(5):634-640. 296. Jones WS, Hellkamp AS, Halperin J, et al. Ef cacy and safety of rivaroxaban compared with warfarin in patients with peripheral artery disease and non-valvular atrial brillation: insights from ROCKET AF. Eur Heart J. 2014;35(4):242-249. 297. Calkins H, Hindricks G, Cappato R, et al. 2017 HRS/EHRA/ECAS/ APHRS/SOLAECE expert consensus statement on catheter and surgical ablation of atrial brillation. Europace. 2018;20(1):e1-e160. 298. Di Biase L, Burkhardt JD, Santangeli P, et al. Periprocedural stroke and bleeding complications in patients undergoing catheter ablation of atrial brillation with different anticoagulation management: results from the Role of Coumadin in Preventing Thromboembolism in Atrial Fibrillation (AF) Patients Undergoing Catheter Ablation (COMPARE) randomized trial. Circulation. 2014;129(25):2638-2644. 299. Cappato R, Marchlinski FE, Hohnloser SH, et al. Uninterrupted rivaroxaban vs. uninterrupted vitamin K antagonists for catheter ablation in non-valvular atrial brillation. Eur Heart J. 2015;36(28): 1805-1811. 300. Calkins H, Willems S, Gerstenfeld EP, et al. Uninterrupted dabigatran versus warfarin for ablation in atrial brillation. N Engl J Med. 2017;376(17):1627-1636. 301. Essebag V, Healey JS, Ayala-Paredes F, et al. Strategy of continued vs interrupted novel oral anticoagulant at time of device surgery in patients with moderate to high risk of arterial thromboembolic events: the BRUISE CONTROL-2 trial. Am Heart J. 2016;173:102- 107. 1196 Evidence-Based Medicine [ 1 5 4 # 5 C H E S T N O V E M B E R 2 0 1 8 ] 302. Cardoso R, Knijnik L, Bhonsale A, et al. An updated meta-analysis of novel oral anticoagulants versus vitamin K antagonists for uninterrupted anticoagulation in atrial brillation catheter ablation. Heart Rhythm. 2018;15(1):107-115. 303.


An updated meta-analysis of novel oral anticoagulants versus vitamin K antagonists for uninterrupted anticoagulation in atrial brillation catheter ablation. Heart Rhythm. 2018;15(1):107-115. 303. Nairooz R, Ayoub K, Sardar P, et al. Uninterrupted new oral anticoagulants compared with uninterrupted vitamin K antagonists in ablation of atrial brillation: a meta-analysis. Can J Cardiol. 2016;32(6):814-823. 304. Daoud EG, Glotzer TV, Wyse DG, et al. Temporal relationship of atrial tachyarrhythmias, cerebrovascular events, and systemic emboli based on stored device data: a subgroup analysis of TRENDS. Heart Rhythm. 2011;8(9):1416-1423. 305. Brambatti M, Connolly SJ, Gold MR, et al. Temporal relationship between subclinical atrial brillation and embolic events. Circulation. 2014;129(21):2094-2099. 306. Gialdini G, Nearing K, Bhave PD, et al. Perioperative atrial brillation and the long-term risk of ischemic stroke. JAMA. 2014;312(6):616-622. 307. Saxena R, Lewis S, Berge E, Sandercock PA, Koudstaal PJ. Risk of early death and recurrent stroke and effect of heparin in 3169 patients with acute ischemic stroke and atrial brillation in the International Stroke Trial. Stroke. 2001;32(10):2333-2337. 308. Hart RG, Coull BM, Hart D. Early recurrent embolism associated with nonvalvular atrial brillation: a retrospective study. Stroke. 1983;14(5):688-693. 309. Berge E, Abdelnoor M, Nakstad PH, Sandset PM. Low molecular- weight heparin versus aspirin in patients with acute ischaemic stroke and atrial brillation: a double-blind randomised study. HAEST Study Group. Heparin in Acute Embolic Stroke Trial. Lancet. 2000;355(9211):1205-1210. 310. Paciaroni M, Agnelli G, Micheli S, Caso V. Ef cacy and safety of anticoagulant treatment in acute cardioembolic stroke: a meta- analysis of randomized controlled trials. Stroke. 2007;38(2):423- 430. 311. CAST: randomised placebo-controlled trial of early aspirin use in 20,000 patients with acute ischaemic stroke. CAST (Chinese Acute Stroke Trial) Collaborative Group. Lancet. 1997;349(9066):1641- 1649. 312. Lin HJ, Wolf PA, Kelly-Hayes M, et al. Stroke severity in atrial brillation. The Framingham Study. Stroke. 1996;27(10):1760-1764. 313.


Stroke severity in atrial brillation. The Framingham Study. Stroke. 1996;27(10):1760-1764. 313. Paciaroni M, Agnelli G, Corea F, et al. Early hemorrhagic transformation of brain infarction: rate, predictive factors, and in uence on clinical outcome: results of a prospective multicenter study. Stroke. 2008;39(8):2249-2256. 314. Paciaroni M, Agnelli G, Falocci N, et al. Early recurrence and cerebral bleeding in patients with acute ischemic stroke and atrial brillation: effect of anticoagulation and its timing: the RAF Study. Stroke. 2015;46(8):2175-2182. 315. Abdul-Rahim AH, Fulton RL, Frank B, et al. Association of improved outcome in acute ischaemic stroke patients with atrial brillation who receive early antithrombotic therapy: analysis from VISTA. Eur J Neurol. 2015;22(7):1048-1055. 316. Kernan WN, Ovbiagele B, Black HR, et al. Guidelines for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2014;45(7): 2160-2236. 317. Kirchhof P, Benussi S, Kotecha D, et al. 2016 ESC Guidelines for the management of atrial brillation developed in collaboration with EACTS [in Polish]. Kardiol Pol. 2016;74(12):1359-1469. 318. Paciaroni M, Agnelli G, Ageno W, Caso V. Timing of anticoagulation therapy in patients with acute ischaemic stroke and atrial brillation. Thromb Haemost. 2016;116(3):410-416. 319. Palm F, Kraus M, Safer A, Wolf J, Becher H, Grau AJ. Management of oral anticoagulation after cardioembolic stroke and stroke survival data from a population based stroke registry (LuSSt). BMC neurology. 2014;14:199. 320. Chamorro A, Vila N, Ascaso C, Blanc R. Heparin in acute stroke with atrial brillation: clinical relevance of very early treatment. Arch Neurol. 1999;56(9):1098-1102. 321. Hahn C, Hill MD. Early Anti-coagulation after ischemic stroke due to atrial brillation is safe and prevents recurrent stroke. Can J Neurol Sci. 2015;42(2):92-95. 322. Hallevi H, Albright KC, Martin-Schild S, et al.


2015;42(2):92-95. 322. Hallevi H, Albright KC, Martin-Schild S, et al. Anticoagulation after cardioembolic stroke: to bridge or not to bridge? Arch Neurol. 2008;65(9):1169-1173. 323. Kim TH, Kim JY, Mun HS, et al. Heparin bridging in warfarin anticoagulation therapy initiation could increase bleeding in non- valvular atrial brillation patients: a multicenter propensity- matched analysis. J Thromb Haemost. 2015;13(2):182-190. 324. Audebert HJ, Schenk B, Tietz V, Schenkel J, Heuschmann PU. Initiation of oral anticoagulation after acute ischaemic stroke or transient ischaemic attack: timing and complications of overlapping heparin or conventional treatment. Cerebrovasc Dis. 2008;26(2): 171-177. 325. Seiffge DJ, Traenka C, Polymeris A, et al. Early start of DOAC after ischemic stroke: Risk of intracranial hemorrhage and recurrent events. Neurology. 2016;87(18):1856-1862. 326. Toyoda K, Arihiro S, Todo K, et al. Trends in oral anticoagulant choice for acute stroke patients with nonvalvular atrial brillation in Japan: the SAMURAI-NVAF study. Int J Stroke. 2015;10(6):836- 842. 327. Arihiro S, Todo K, Koga M, et al. Three-month risk-bene t pro le of anticoagulation after stroke with atrial brillation: the SAMURAI-Nonvalvular Atrial Fibrillation (NVAF) study. Int J Stroke. 2016;11(5):565-574. 328. Terent A, sberg S, Oldgren J, Hijazi Z, Norrving B. Antikoagulantia efter akut ischemisk stroke med f rmaks immer Fr gan om r tt tidpunkt f r ins ttning kr ver randomiserad klinisk pr vning [in Swedish]. Lakartidningen. 2016;113. 329. Hong KS, Choi YJ, Kwon SU; Triple AXEL Investigators. Rationale and design of Triple AXEL: trial for early anticoagulation in acute ischemic stroke patients with nonvalvular atrial brillation. Int J Stroke. 2015;10(1):128-133. 330. Lovelock CE, Molyneux AJ, Rothwell PM, Oxford Vascular S. Change in incidence and aetiology of intracerebral haemorrhage in Oxfordshire, UK, between 1981 and 2006: a population-based study. Lancet Neurol. 2007;6(6):487-493. 331.


Lovelock CE, Molyneux AJ, Rothwell PM, Oxford Vascular S. Change in incidence and aetiology of intracerebral haemorrhage in Oxfordshire, UK, between 1981 and 2006: a population-based study. Lancet Neurol. 2007;6(6):487-493. 331. Horstmann S, Rizos T, Jenetzky E, Gumbinger C, Hacke W, Veltkamp R. Prevalence of atrial brillation in intracerebral hemorrhage. Eur J Neurol. 2014;21(4):570-576. 332. Chao TF, Liu CJ, Liao JN, et al. Use of oral anticoagulants for stroke prevention in patients with atrial brillation who have a history of intracranial hemorrhage. Circulation. 2016;133(16):1540-1547. 333. Poon MT, Fonville AF, Al-Shahi Salman R. Long-term prognosis after intracerebral haemorrhage: systematic review and meta- analysis. J Neurol Neurosurg Psychiatry. 2014;85(6):660-667. 334. Charidimou A, Schmitt A, Wilson D, et al. The Cerebral Haemorrhage Anatomical RaTing inStrument (CHARTS): development and assessment of reliability. J Neurol Sci. 2017;372: 178-183. 335. Knudsen KA, Rosand J, Karluk D, Greenberg SM. Clinical diagnosis of cerebral amyloid angiopathy: validation of the Boston criteria. Neurology. 2001;56(4):537-539. 336. Charidimou A, Imaizumi T, Moulin S, et al. Brain hemorrhage recurrence, small vessel disease type, and cerebral microbleeds: a meta-analysis. Neurology. 2017;89(8):820-829. 337. Wilson D, Charidimou A, Ambler G, et al. Recurrent stroke risk and cerebral microbleed burden in ischemic stroke and TIA: a meta-analysis. Neurology. 2016;87(14):1501-1510. 338. Wilson D, Werring DJ. Antithrombotic therapy in patients with cerebral microbleeds. Curr Opin Neurol. 2017;30(1):38-47. 339. Eckman MH, Rosand J, Knudsen KA, Singer DE, Greenberg SM. Can patients be anticoagulated after intracerebral hemorrhage? A decision analysis. Stroke. 2003;34(7):1710-1716. 340. Murthy SB, Gupta A, Merkler AE, et al. Restarting anticoagulant therapy after intracranial hemorrhage: a systematic review and meta-analysis. Stroke. 2017;48(6):1594-1600. 341. Orken DN, Kenangil G, Ozkurt H, et al. Prevention of deep venous thrombosis and pulmonary embolism in patients with acute intracerebral hemorrhage. Neurologist. 2009;15(6):329-331. 342.


Prevention of deep venous thrombosis and pulmonary embolism in patients with acute intracerebral hemorrhage. Neurologist. 2009;15(6):329-331. 342. Dickmann U, Voth E, Schicha H, Henze T, Prange H, Emrich D. Heparin therapy, deep-vein thrombosis and pulmonary embolism after intracerebral hemorrhage. Klin Wochenschr. 1988;66(23): 1182-1183. 343. Majeed A, Kim YK, Roberts RS, Holmstrom M, Schulman S. Optimal timing of resumption of warfarin after intracranial hemorrhage. Stroke. 2010;41(12):2860-2866. 344. Wilson D, Seiffge DJ, Traenka C, et al. Outcome of intracerebral hemorrhage associated with different oral anticoagulants. Neurology. 2017;88(18):1693-1700. 345. Lewalter T, Kanagaratnam P, Schmidt B, et al. Ischaemic stroke prevention in patients with atrial brillation and high bleeding risk: opportunities and challenges for percutaneous left atrial appendage occlusion. Europace. 2014;16(5):626-630. 346. Boersma LV, Ince H, Kische S, et al. Ef cacy and safety of left atrial appendage closure with WATCHMAN in patients with or without contraindication to oral anticoagulation: 1-year follow-up outcome data of the EWOLUTION trial. Heart Rhythm. 2017;14(9):1302- 1308. 347. Renou P, Thambo JB, Iriart X, et al. Left Atrial Appendage Closure in Patients with Atrial Fibrillation and Previous Intracerebral Hemorrhage. J Stroke Cerebrovasc Dis. 2017;26(3):545-551. 348. Horstmann S, Zugck C, Krumsdorf U, et al. Left atrial appendage occlusion in atrial brillation after intracranial hemorrhage. Neurology. 2014;82(2):135-138. 349. Mineva PP, Manchev IC, Hadjiev DI. Prevalence and outcome of asymptomatic carotid stenosis: a population-based ultrasonographic study. Eur J Neurol. 2002;9(4):383-388. 350. Lehtola H, Airaksinen KEJ, Hartikainen P, et al. Stroke recurrence in patients with atrial brillation: concomitant carotid artery stenosis doubles the risk. Eur J Neurol. 2017;24(5):719-725. 351. Bonati LH, Dobson J, Featherstone RL, et al. Long-term outcomes after stenting versus endarterectomy for treatment of symptomatic carotid stenosis: the International Carotid Stenting Study (ICSS) randomised trial. Lancet. 2015;385(9967):529-538. 352. Saver JL. Cryptogenic stroke. N Engl J Med. 2016;375(11):e26. 353.