Korean Circulation Journal

The Korean Society of Cardiology (대한심장학회)
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Anticoagulation for Stroke Prevention in Older Adults with Atrial Fibrillation and Comorbidity: Current Evidence and Treatment Challenges

  • Sabbag, Avi (Department of Cardiovascular Diseases, Mayo Clinic) ;
  • Yao, Xiaoxi (Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery) ;
  • Siontis, Konstantinos C. (Department of Cardiovascular Diseases, Mayo Clinic) ;
  • Noseworthy, Peter A. (Department of Cardiovascular Diseases, Mayo Clinic)
  • Received : 2018.08.09
  • Accepted : 2018.08.30
  • Published : 2018.10.31
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Abstract

The burden of atrial fibrillation (AF) is projected to increase substantially over the next decade in parallel with the aging of the population. The increasing age, level of comorbidity, and polypharmacy will complicate the treatment of older adults with AF. For instance, advanced age and chronic kidney disease have been shown to increase the risk of both thromboembolism and bleeding in patients with AF. Frailty, recurrent falls and polypharmacy, while very common among elderly patients with AF, are often overlooked in the clinical decision making despite their significant interaction with oral anticoagulant (OAC) and profound impact on the patient's clinical outcomes. Such factors should be recognized, evaluated and considered in a comprehensive decision-making process. The introduction of non-vitamin K oral anticoagulants has radically changed the management of AF allowing for a more individualized selection of OAC. An understanding of the available data regarding the performance of each of the available OAC in a variety of at risk patient populations is paramount for the safe and effective management of this patient population. The aim of this review is to appraise the current evidence, point out the gaps in knowledge, and provide recommendations regarding stroke prevention in older adults with AF and comorbid conditions.

Keywords

References

  1. Chugh SS, Havmoeller R, Narayanan K, et al. Worldwide epidemiology of atrial fibrillation: a Global Burden of Disease 2010 study. Circulation 2014;129:837-47. https://doi.org/10.1161/CIRCULATIONAHA.113.005119
  2. Miyasaka Y, Barnes ME, Gersh BJ, et al. Secular trends in incidence of atrial fibrillation in Olmsted County, Minnesota, 1980 to 2000, and implications on the projections for future prevalence. Circulation 2006;114:119-25. https://doi.org/10.1161/CIRCULATIONAHA.105.595140
  3. Stroke Risk in Atrial Fibrillation Working Group. Independent predictors of stroke in patients with atrial fibrillation: a systematic review. Neurology 2007;69:546-54. https://doi.org/10.1212/01.wnl.0000267275.68538.8d
  4. Lopes RD, Guimaraes PO, Kolls BJ, et al. Intracranial hemorrhage in patients with atrial fibrillation receiving anticoagulation therapy. Blood 2017;129:2980-7. https://doi.org/10.1182/blood-2016-08-731638
  5. Kooiman J, van de Peppel WR, van der Meer FJ, Huisman MV. Incidence of chronic kidney disease in patients with atrial fibrillation and its relevance for prescribing new oral antithrombotic drugs. J Thromb Haemost 2011;9:1652-3. https://doi.org/10.1111/j.1538-7836.2011.04347.x
  6. Hart RG, Eikelboom JW, Brimble KS, McMurtry MS, Ingram AJ. Stroke prevention in atrial fibrillation patients with chronic kidney disease. Can J Cardiol 2013;29:S71-8. https://doi.org/10.1016/j.cjca.2013.04.005
  7. Soliman EZ, Prineas RJ, Go AS, et al.Chronic Renal Insufficiency Cohort (CRIC) Study Group. Chronic kidney disease and prevalent atrial fibrillation: the Chronic Renal Insufficiency Cohort (CRIC). Am Heart J 2010;159:1102-7. https://doi.org/10.1016/j.ahj.2010.03.027
  8. Jha V, Garcia-Garcia G, Iseki K, et al. Chronic kidney disease: global dimension and perspectives. Lancet 2013;382:260-72. https://doi.org/10.1016/S0140-6736(13)60687-X
  9. Kaufman DW, Kelly JP, Rosenberg L, Anderson TE, Mitchell AA. Recent patterns of medication use in the ambulatory adult population of the United States: the Slone survey. JAMA 2002;287:337-44. https://doi.org/10.1001/jama.287.3.337
  10. 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 fibrillation: the Euro Heart Survey. Chest 2010;138:1093-100. https://doi.org/10.1378/chest.10-0134
  11. Lip GY, Nieuwlaat R, Pisters R, Lane DA, Crijns HJ. Refining clinical risk stratification for predicting stroke and thromboembolism in atrial fibrillation using a novel risk factor-based approach: the euro heart survey on atrial fibrillation. Chest 2010;137:263-72. https://doi.org/10.1378/chest.09-1584
  12. Kato ET, Giugliano RP, Ruff CT, et al. Efficacy and safety of edoxaban in elderly patients with atrial fibrillation in the ENGAGE AF-TIMI 48 trial. J Am Heart Assoc 2016;5:e003432.
  13. Mant J, Hobbs FD, Fletcher K, et al. Warfarin versus aspirin for stroke prevention in an elderly community population with atrial fibrillation (the Birmingham Atrial Fibrillation Treatment of the Aged Study, BAFTA): a randomised controlled trial. Lancet 2007;370:493-503. https://doi.org/10.1016/S0140-6736(07)61233-1
  14. Hart RG, Benavente O, McBride R, Pearce LA. Antithrombotic therapy to prevent stroke in patients with atrial fibrillation: a meta-analysis. Ann Intern Med 1999;131:492-501.
  15. Chao TF, Liu CJ, Lin YJ, et al. Oral anticoagulation in very elderly patients with atrial fibrillation: a nationwide cohort study. Circulation 2018;138:37-47. https://doi.org/10.1161/CIRCULATIONAHA.117.031658
  16. Lauw MN, Eikelboom JW, Coppens M, et al. Effects of dabigatran according to age in atrial fibrillation. Heart 2017;103:1015-23. https://doi.org/10.1136/heartjnl-2016-310358
  17. Romanelli RJ, Nolting L, Dolginsky M, Kym E, Orrico KB. Dabigatran versus warfarin for atrial fibrillation in real-world clinical practice: a systematic review and meta-analysis. Circ Cardiovasc Qual Outcomes 2016;9:126-34. https://doi.org/10.1161/CIRCOUTCOMES.115.002369
  18. Patel MR, Mahaffey KW, Garg J, et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med 2011;365:883-91. https://doi.org/10.1056/NEJMoa1009638
  19. Halperin JL, Hankey GJ, Wojdyla DM, et al. Efficacy and safety of rivaroxaban compared with warfarin among elderly patients with nonvalvular atrial fibrillation in the Rivaroxaban Once Daily, Oral, Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF). Circulation 2014;130:138-46. https://doi.org/10.1161/CIRCULATIONAHA.113.005008
  20. Granger CB, Alexander JH, McMurray JJ, et al. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med 2011;365:981-92. https://doi.org/10.1056/NEJMoa1107039
  21. Halvorsen S, Atar D, Yang H, et al. Efficacy and safety of apixaban compared with warfarin according to age for stroke prevention in atrial fibrillation: observations from the ARISTOTLE trial. Eur Heart J 2014;35:1864-72. https://doi.org/10.1093/eurheartj/ehu046
  22. Giugliano RP, Ruff CT, Braunwald E, et al. Edoxaban versus warfarin in patients with atrial fibrillation. N Engl J Med 2013;369:2093-104. https://doi.org/10.1056/NEJMoa1310907
  23. Kanapuru B, Ershler WB. Inflammation, coagulation, and the pathway to frailty. Am J Med 2009;122:605-13. https://doi.org/10.1016/j.amjmed.2009.01.030
  24. Rockwood K, Song X, MacKnight C, et al. A global clinical measure of fitness and frailty in elderly people. CMAJ 2005;173:489-95. https://doi.org/10.1503/cmaj.050051
  25. Gale CR, Cooper C, Sayer AA. Prevalence of frailty and disability: findings from the English Longitudinal Study of Ageing. Age Ageing 2015;44:162-5. https://doi.org/10.1093/ageing/afu148
  26. Harttgen K, Kowal P, Strulik H, Chatterji S, Vollmer S. Patterns of frailty in older adults: comparing results from higher and lower income countries using the Survey of Health, Ageing and Retirement in Europe (SHARE) and the Study on Global AGEing and Adult Health (SAGE). PLoS One 2013;8:e75847. https://doi.org/10.1371/journal.pone.0075847
  27. Bandeen-Roche K, Seplaki CL, Huang J, et al. Frailty in older adults: a nationally representative profile in the United States. J Gerontol A Biol Sci Med Sci 2015;70:1427-34. https://doi.org/10.1093/gerona/glv133
  28. Fried LP, Tangen CM, Walston J, et al. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci 2001;56:M146-57. https://doi.org/10.1093/gerona/56.3.M146
  29. Rockwood K, Howlett SE, MacKnight C, et al. Prevalence, attributes, and outcomes of fitness and frailty in community-dwelling older adults: report from the Canadian study of health and aging. J Gerontol A Biol Sci Med Sci 2004;59:1310-7. https://doi.org/10.1093/gerona/59.12.1310
  30. Shamliyan T, Talley KM, Ramakrishnan R, Kane RL. Association of frailty with survival: a systematic literature review. Ageing Res Rev 2013;12:719-36. https://doi.org/10.1016/j.arr.2012.03.001
  31. Sourial N, Wolfson C, Bergman H, et al. A correspondence analysis revealed frailty deficits aggregate and are multidimensional. J Clin Epidemiol 2010;63:647-54. https://doi.org/10.1016/j.jclinepi.2009.08.007
  32. Polidoro A, Stefanelli F, Ciacciarelli M, Pacelli A, Di Sanzo D, Alessandri C. Frailty in patients affected by atrial fibrillation. Arch Gerontol Geriatr 2013;57:325-7. https://doi.org/10.1016/j.archger.2013.04.014
  33. Kim SW, Yoon SJ, Choi JY, et al. Clinical implication of frailty assessment in older patients with atrial fibrillation. Arch Gerontol Geriatr 2017;70:1-7. https://doi.org/10.1016/j.archger.2016.12.001
  34. Lefebvre MC, St-Onge M, Glazer-Cavanagh M, et al. The effect of bleeding risk and frailty status on anticoagulation patterns in octogenarians with atrial fibrillation: the FRAIL-AF study. Can J Cardiol 2016;32:169-76. https://doi.org/10.1016/j.cjca.2015.05.012
  35. Perera V, Bajorek BV, Matthews S, Hilmer SN. The impact of frailty on the utilisation of antithrombotic therapy in older patients with atrial fibrillation. Age Ageing 2009;38:156-62.
  36. Martinez BK, Sood NA, Bunz TJ, Coleman CI. Effectiveness and safety of apixaban, dabigatran, and rivaroxaban versus warfarin in frail patients with nonvalvular atrial fibrillation. J Am Heart Assoc 2018;7:e008643.
  37. Segal JB, Chang HY, Du Y, Walston JD, Carlson MC, Varadhan R. Development of a claims-based frailty indicator anchored to a well-established frailty phenotype. Med Care 2017;55:716-22. https://doi.org/10.1097/MLR.0000000000000729
  38. Andrassy KM. Comments on 'KDIGO 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease'. Kidney Int 2013;84:622-3.
  39. Yagmur E, Frank RD, Neulen J, Floege J, Muhlfeld AS. Platelet Hyperaggregability is highly prevalent in patients with chronic kidney disease: an underestimated risk indicator of thromboembolic events. Clin Appl Thromb Hemost 2015;21:132-8. https://doi.org/10.1177/1076029613490828
  40. Nelson SE, Shroff GR, Li S, Herzog CA. Impact of chronic kidney disease on risk of incident atrial fibrillation and subsequent survival in Medicare patients. J Am Heart Assoc 2012;1:e002097.
  41. Hwang HS, Park MW, Yoon HE, et al. Clinical significance of chronic kidney disease and atrial fibrillation on morbidity and mortality in patients with acute myocardial infarction. Am J Nephrol 2014;40:345-52. https://doi.org/10.1159/000368422
  42. Watanabe H, Watanabe T, Sasaki S, Nagai K, Roden DM, Aizawa Y. Close bidirectional relationship between chronic kidney disease and atrial fibrillation: the Niigata preventive medicine study. Am Heart J 2009;158:629-36. https://doi.org/10.1016/j.ahj.2009.06.031
  43. Bansal N, Fan D, Hsu CY, Ordonez JD, Marcus GM, Go AS. Incident atrial fibrillation and risk of end-stage renal disease in adults with chronic kidney disease. Circulation 2013;127:569-74. https://doi.org/10.1161/CIRCULATIONAHA.112.123992
  44. Olesen JB, Lip GY, Kamper AL, et al. Stroke and bleeding in atrial fibrillation with chronic kidney disease. N Engl J Med 2012;367:625-35. https://doi.org/10.1056/NEJMoa1105594
  45. Molshatzki N, Orion D, Tsabari R, et al. Chronic kidney disease in patients with acute intracerebral hemorrhage: association with large hematoma volume and poor outcome. Cerebrovasc Dis 2011;31:271-7. https://doi.org/10.1159/000322155
  46. Lee JG, Lee KB, Jang IM, et al. Low glomerular filtration rate increases hemorrhagic transformation in acute ischemic stroke. Cerebrovasc Dis 2013;35:53-9. https://doi.org/10.1159/000345087
  47. Sohal AS, Gangji AS, Crowther MA, Treleaven D. Uremic bleeding: pathophysiology and clinical risk factors. Thromb Res 2006;118:417-22. https://doi.org/10.1016/j.thromres.2005.03.032
  48. Benigni A, Boccardo P, Galbusera M, et al. Reversible activation defect of the platelet glycoprotein IIb-IIIa complex in patients with uremia. Am J Kidney Dis 1993;22:668-76. https://doi.org/10.1016/S0272-6386(12)80429-X
  49. Ng KP, Edwards NC, Lip GY, Townend JN, Ferro CJ. Atrial fibrillation in CKD: balancing the risks and benefits of anticoagulation. Am J Kidney Dis 2013;62:615-32. https://doi.org/10.1053/j.ajkd.2013.02.381
  50. Kirchhof P, Benussi S, Kotecha D, et al.ESC Scientific Document Group. 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur Heart J 2016;37:2893-962. https://doi.org/10.1093/eurheartj/ehw210
  51. January CT, Wann LS, Alpert JS, et al. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol 2014;64:e1-76. https://doi.org/10.1016/j.jacc.2014.03.022
  52. Piccini JP, Stevens SR, Chang Y, et al. Renal dysfunction as a predictor of stroke and systemic embolism in patients with nonvalvular atrial fibrillation: validation of the R2CHADS2 index in the ROCKET AF (Rivaroxaban Once-daily, oral, direct factor Xa inhibition Compared with vitamin K antagonism for prevention of stroke and Embolism Trial in Atrial Fibrillation) and ATRIA (AnTicoagulation and Risk factors In Atrial fibrillation) study cohorts. Circulation 2013;127:224-32. https://doi.org/10.1161/CIRCULATIONAHA.112.107128
  53. Roldan V, Marin F, Manzano-Fernandez S, et al. Does chronic kidney disease improve the predictive value of the CHADS2 and CHA2DS2-VASc stroke stratification risk scores for atrial fibrillation? Thromb Haemost 2013;109:956-60. https://doi.org/10.1160/TH13-01-0054
  54. Lau YC, Proietti M, Guiducci E, Blann AD, Lip GY. Atrial fibrillation and thromboembolism in patients with chronic kidney disease. J Am Coll Cardiol 2016;68:1452-64. https://doi.org/10.1016/j.jacc.2016.06.057
  55. Lip GY, Skjoth F, Nielsen PB, Kjaeldgaard JN, Larsen TB. The HAS-BLED, ATRIA, and ORBIT bleeding scores in atrial fibrillation patients using non-vitamin K antagonist oral anticoagulants. Am J Med 2018;131:574.e13-27. https://doi.org/10.1016/j.amjmed.2017.11.046
  56. Olesen JB, Lip GY, Lindhardsen J, et al. Risks of thromboembolism and bleeding with thromboprophylaxis in patients with atrial fibrillation: a net clinical benefit analysis using a 'real world' nationwide cohort study. Thromb Haemost 2011;106:739-49. https://doi.org/10.1160/TH11-05-0364
  57. Providencia R, Marijon E, Boveda S, et al. Meta-analysis of the influence of chronic kidney disease on the risk of thromboembolism among patients with nonvalvular atrial fibrillation. Am J Cardiol 2014;114:646-53. https://doi.org/10.1016/j.amjcard.2014.05.048
  58. Bonde AN, Lip GY, Kamper AL, et al. Net clinical benefit of antithrombotic therapy in patients with atrial fibrillation and chronic kidney disease: a nationwide observational cohort study. J Am Coll Cardiol 2014;64:2471-82. https://doi.org/10.1016/j.jacc.2014.09.051
  59. Friberg L, Rosenqvist M, Lip GY. Evaluation of risk stratification schemes for ischaemic stroke and bleeding in 182,678 patients with atrial fibrillation: the Swedish Atrial Fibrillation cohort study. Eur Heart J 2012;33:1500-10. https://doi.org/10.1093/eurheartj/ehr488
  60. Yang F, Hellyer JA, Than C, et al. Warfarin utilisation and anticoagulation control in patients with atrial fibrillation and chronic kidney disease. Heart 2017;103:818-26. https://doi.org/10.1136/heartjnl-2016-309266
  61. Bohula EA, Giugliano RP, Ruff CT, et al. Impact of renal function on outcomes with edoxaban in the ENGAGE AF-TIMI 48 trial. Circulation 2016;134:24-36. https://doi.org/10.1161/CIRCULATIONAHA.116.022361
  62. Fox KA, Piccini JP, Wojdyla D, et al. Prevention of stroke and systemic embolism with rivaroxaban compared with warfarin in patients with non-valvular atrial fibrillation and moderate renal impairment. Eur Heart J 2011;32:2387-94. https://doi.org/10.1093/eurheartj/ehr342
  63. Hijazi Z, Hohnloser SH, Oldgren J, et al. Efficacy and safety of dabigatran compared with warfarin in relation to baseline renal function in patients with atrial fibrillation: a RE-LY (Randomized Evaluation of Long-term Anticoagulation Therapy) trial analysis. Circulation 2014;129:961-70. https://doi.org/10.1161/CIRCULATIONAHA.113.003628
  64. Hohnloser SH, Hijazi Z, Thomas L, et al. Efficacy of apixaban when compared with warfarin in relation to renal function in patients with atrial fibrillation: insights from the ARISTOTLE trial. Eur Heart J 2012;33:2821-30. https://doi.org/10.1093/eurheartj/ehs274
  65. Kimachi M, Furukawa TA, Kimachi K, Goto Y, Fukuma S, Fukuhara S. Direct oral anticoagulants versus warfarin for preventing stroke and systemic embolic events among atrial fibrillation patients with chronic kidney disease. Cochrane Database Syst Rev 2017:CD011373.
  66. Seliger SL, Gillen DL, Tirschwell D, Wasse H, Kestenbaum BR, Stehman-Breen CO. Risk factors for incident stroke among patients with end-stage renal disease. J Am Soc Nephrol 2003;14:2623-31. https://doi.org/10.1097/01.ASN.0000088722.56342.A8
  67. Zimmerman D, Sood MM, Rigatto C, Holden RM, Hiremath S, Clase CM. Systematic review and meta-analysis of incidence, prevalence and outcomes of atrial fibrillation in patients on dialysis. Nephrol Dial Transplant 2012;27:3816-22. https://doi.org/10.1093/ndt/gfs416
  68. Poli D, Antonucci E, Zanazzi M, et al. Impact of glomerular filtration estimate on bleeding risk in very old patients treated with vitamin K antagonists. Results of EPICA study on the behalf of FCSA (Italian Federation of Anticoagulation Clinics). Thromb Haemost 2012;107:1100-6. https://doi.org/10.1160/TH11-10-0721
  69. Shah M, Avgil Tsadok M, Jackevicius CA, et al. Warfarin use and the risk for stroke and bleeding in patients with atrial fibrillation undergoing dialysis. Circulation 2014;129:1196-203. https://doi.org/10.1161/CIRCULATIONAHA.113.004777
  70. Galloway PA, El-Damanawi R, Bardsley V, et al. Vitamin K antagonists predispose to calciphylaxis in patients with end-stage renal disease. Nephron 2015;129:197-201. https://doi.org/10.1159/000371449
  71. Lomashvili KA, Wang X, Wallin R, O'Neill WC. Matrix Gla protein metabolism in vascular smooth muscle and role in uremic vascular calcification. J Biol Chem 2011;286:28715-22. https://doi.org/10.1074/jbc.M111.251462
  72. Nigwekar SU, Zhao S, Wenger J, et al. A nationally representative study of calcific uremic arteriolopathy risk factors. J Am Soc Nephrol 2016;27:3421-9. https://doi.org/10.1681/ASN.2015091065
  73. Chan KE, Edelman ER, Wenger JB, Thadhani RI, Maddux FW. Dabigatran and rivaroxaban use in atrial fibrillation patients on hemodialysis. Circulation 2015;131:972-9. https://doi.org/10.1161/CIRCULATIONAHA.114.014113
  74. Stangier J, Rathgen K, Stahle H, Mazur D. Influence of renal impairment on the pharmacokinetics and pharmacodynamics of oral dabigatran etexilate: an open-label, parallel-group, single-centre study. Clin Pharmacokinet 2010;49:259-68. https://doi.org/10.2165/11318170-000000000-00000
  75. Kubitza D, Becka M, Mueck W, et al. Effects of renal impairment on the pharmacokinetics, pharmacodynamics and safety of rivaroxaban, an oral, direct factor Xa inhibitor. Br J Clin Pharmacol 2010;70:703-12. https://doi.org/10.1111/j.1365-2125.2010.03753.x
  76. Wang X, Tirucherai G, Marbury TC, et al. Pharmacokinetics, pharmacodynamics, and safety of apixaban in subjects with end-stage renal disease on hemodialysis. J Clin Pharmacol 2016;56:628-36. https://doi.org/10.1002/jcph.628
  77. Mavrakanas TA, Samer CF, Nessim SJ, Frisch G, Lipman ML. Apixaban pharmacokinetics at steady state in hemodialysis patients. J Am Soc Nephrol 2017;28:2241-8. https://doi.org/10.1681/ASN.2016090980
  78. Chokesuwattanaskul R, Thongprayoon C, Tanawuttiwat T, Kaewput W, Pachariyanon P, Cheungpasitporn W. Safety and efficacy of apixaban versus warfarin in patients with end-stage renal disease: meta-analysis. Pacing Clin Electrophysiol 2018;41:627-34. https://doi.org/10.1111/pace.13331
  79. Siontis KC, Zhang X, Eckard A, et al. Outcomes associated with apixaban use in end-stage kidney disease patients with atrial fibrillation in the United States. Circulation. 2018 [Epub ahead of print].
  80. Koretsune Y, Yamashita T, Kimura T, Fukuzawa M, Abe K, Yasaka M. Short-term safety and plasma concentrations of edoxaban in Japanese patients with non-valvular atrial fibrillation and severe renal impairment. Circ J 2015;79:1486-95. https://doi.org/10.1253/circj.CJ-14-0942
  81. De Vriese AS, Caluwe R, Bailleul E, et al. Dose-finding study of rivaroxaban in hemodialysis patients. Am J Kidney Dis 2015;66:91-8. https://doi.org/10.1053/j.ajkd.2015.01.022
  82. Steffel J, Verhamme P, Potpara TS, et al. The 2018 European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation. Eur Heart J 2018;39:1330-93. https://doi.org/10.1093/eurheartj/ehy136
  83. January CT, Wann LS, Alpert JS, et al. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society. Circulation 2014;130:e199-267.
  84. Brodsky SV, Collins M, Park E, et al. Warfarin therapy that results in an international normalization ratio above the therapeutic range is associated with accelerated progression of chronic kidney disease. Nephron Clin Pract 2010;115:c142-6. https://doi.org/10.1159/000312877
  85. Brodsky SV, Nadasdy T, Rovin BH, et al. Warfarin-related nephropathy occurs in patients with and without chronic kidney disease and is associated with an increased mortality rate. Kidney Int 2011;80:181-9. https://doi.org/10.1038/ki.2011.44
  86. Brodsky SV, Satoskar A, Chen J, et al. Acute kidney injury during warfarin therapy associated with obstructive tubular red blood cell casts: a report of 9 cases. Am J Kidney Dis 2009;54:1121-6. https://doi.org/10.1053/j.ajkd.2009.04.024
  87. Ware K, Brodsky P, Satoskar AA, et al. Warfarin-related nephropathy modeled by nephron reduction and excessive anticoagulation. J Am Soc Nephrol 2011;22:1856-62. https://doi.org/10.1681/ASN.2010101110
  88. Bohm M, Ezekowitz MD, Connolly SJ, et al. Changes in renal function in patients with atrial fibrillation: an analysis from the RE-LY trial. J Am Coll Cardiol 2015;65:2481-93. https://doi.org/10.1016/j.jacc.2015.03.577
  89. Hijazi Z, Hohnloser SH, Andersson U, et al. Efficacy and safety of apixaban compared with warfarin in patients with atrial fibrillation in relation to renal function over time: Insights from the aristotle randomized clinical trial. JAMA Cardiol 2016;1:451-60. https://doi.org/10.1001/jamacardio.2016.1170
  90. Chan YH, Yeh YH, Hsieh MY, et al. The risk of acute kidney injury in Asians treated with apixaban, rivaroxaban, dabigatran, or warfarin for non-valvular atrial fibrillation: a nationwide cohort study in Taiwan. Int J Cardiol 2018;265:83-9. https://doi.org/10.1016/j.ijcard.2018.02.075
  91. Yao X, Tangri N, Gersh BJ, et al. Renal outcomes in anticoagulated patients with atrial fibrillation. J Am Coll Cardiol 2017;70:2621-32. https://doi.org/10.1016/j.jacc.2017.09.1087
  92. Banerjee A, Clementy N, Haguenoer K, Fauchier L, Lip GY. Prior history of falls and risk of outcomes in atrial fibrillation: the Loire Valley Atrial Fibrillation Project. Am J Med 2014;127:972-8. https://doi.org/10.1016/j.amjmed.2014.05.035
  93. Man-Son-Hing M, Nichol G, Lau A, Laupacis A. Choosing antithrombotic therapy for elderly patients with atrial fibrillation who are at risk for falls. Arch Intern Med 1999;159:677-85. https://doi.org/10.1001/archinte.159.7.677
  94. Gage BF, Birman-Deych E, Kerzner R, Radford MJ, Nilasena DS, Rich MW. Incidence of intracranial hemorrhage in patients with atrial fibrillation who are prone to fall. Am J Med 2005;118:612-7. https://doi.org/10.1016/j.amjmed.2005.02.022
  95. Garwood CL, Corbett TL. Use of anticoagulation in elderly patients with atrial fibrillation who are at risk for falls. Ann Pharmacother 2008;42:523-32. https://doi.org/10.1345/aph.1K498
  96. Donze J, Clair C, Hug B, et al. Risk of falls and major bleeds in patients on oral anticoagulation therapy. Am J Med 2012;125:773-8. https://doi.org/10.1016/j.amjmed.2012.01.033
  97. Steffel J, Giugliano RP, Braunwald E, et al. Edoxaban versus warfarin in atrial fibrillation patients at risk of falling: ENGAGE AF-TIMI 48 analysis. J Am Coll Cardiol 2016;68:1169-78. https://doi.org/10.1016/j.jacc.2016.06.034
  98. Rao MP, Vinereanu D, Wojdyla DM, et al. Clinical outcomes and history of fall in patients with atrial fibrillation treated with oral anticoagulation: insights from the ARISTOTLE trial. Am J Med 2018;131:269-275.e2. https://doi.org/10.1016/j.amjmed.2017.10.036
  99. Bushardt RL, Massey EB, Simpson TW, Ariail JC, Simpson KN. Polypharmacy: misleading, but manageable. Clin Interv Aging 2008;3:383-9. https://doi.org/10.2147/CIA.S2468
  100. Proietti M, Raparelli V, Olshansky B, Lip GY. Polypharmacy and major adverse events in atrial fibrillation: observations from the AFFIRM trial. Clin Res Cardiol 2016;105:412-20. https://doi.org/10.1007/s00392-015-0936-y
  101. Wang Y, Singh S, Bajorek B. Old age, high risk medication, polypharmacy: a 'trilogy' of risks in older patients with atrial fibrillation. Pharm Pract (Granada) 2016;14:706. https://doi.org/10.18549/PharmPract.2016.02.706
  102. Gomez C, Vega-Quiroga S, Bermejo-Pareja F, Medrano MJ, Louis ED, Benito-Leon J. Polypharmacy in the elderly: a marker of increased risk of mortality in a population-based prospective study (NEDICES). Gerontology 2015;61:301-9.
  103. Maher RL, Hanlon J, Hajjar ER. Clinical consequences of polypharmacy in elderly. Expert Opin Drug Saf 2014;13:57-65.
  104. Lim LM, McStea M, Chung WW, et al. Prevalence, risk factors and health outcomes associated with polypharmacy among urban community-dwelling older adults in multi-ethnic Malaysia. PLoS One 2017;12:e0173466. https://doi.org/10.1371/journal.pone.0173466
  105. Jaspers Focks J, Brouwer MA, Wojdyla DM, et al. Polypharmacy and effects of apixaban versus warfarin in patients with atrial fibrillation: post hoc analysis of the ARISTOTLE trial. BMJ 2016;353:i2868.
  106. 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:e152S-184S. https://doi.org/10.1378/chest.11-2295
  107. Battistella M, Mamdami MM, Juurlink DN, Rabeneck L, Laupacis A. Risk of upper gastrointestinal hemorrhage in warfarin users treated with nonselective NSAIDs or COX-2 inhibitors. Arch Intern Med 2005;165:189-92. https://doi.org/10.1001/archinte.165.2.189
  108. Chang SH, Chou IJ, Yeh YH, et al. Association between use of non-vitamin K oral anticoagulants with and without concurrent medications and risk of major bleeding in nonvalvular atrial fibrillation. JAMA 2017;318:1250-9. https://doi.org/10.1001/jama.2017.13883
  109. Piccini JP, Hellkamp AS, Washam JB, et al. Polypharmacy and the efficacy and safety of rivaroxaban versus warfarin in the prevention of stroke in patients with nonvalvular atrial fibrillation. Circulation 2016;133:352-60. https://doi.org/10.1161/CIRCULATIONAHA.115.018544

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