Subscribe to RSS
DOI: 10.1055/s-0040-1721665
Use of Non-vitamin K Antagonist Oral Anticoagulants for Stroke Prevention across the Stroke Spectrum: Progress and Prospects
Funding This study was supported by Bayer.Abstract
Multiple randomized controlled trials and many real-world evidence studies have consistently shown that non-vitamin K antagonist oral anticoagulants (NOACs) are preferable to vitamin K antagonists for thromboembolic stroke prevention in the majority of patients with atrial fibrillation (AF). However, their role in the management of patients with AF and comorbidities, as well as in other patient populations with a high risk of stroke, such as patients with prior embolic stroke of undetermined source (ESUS) and those with atherosclerosis, is less clear. There is now increasing evidence suggesting that NOACs have a beneficial effect in the prevention of stroke in patients with AF and comorbidities, such as renal impairment and diabetes. In addition, while studies investigating the efficacy and safety of NOACs for the prevention of secondary stroke in patients with a history of ESUS demonstrated neutral results, subanalyses suggested potential benefits in certain subgroups of patients with ESUS. One NOAC, rivaroxaban, has also recently been found to be effective in reducing the risk of stroke in patients with chronic cardiovascular disease including coronary artery disease and peripheral artery disease, further broadening the patient groups that may benefit from NOACs. In this article, we will review recent evidence for the use of NOACs across the stroke spectrum in detail, and discuss the progress and future prospects in the different stroke areas.
Keywords
stroke prevention - non-vitamin K antagonist oral anticoagulants - atrial fibrillation - embolic stroke of undetermined source - atherosclerosisPublication History
Received: 16 July 2020
Accepted: 31 October 2020
Article published online:
07 January 2021
© 2021. Thieme. All rights reserved.
Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany
-
References
- 1 World Health Organization, The top 10 causes of death. 2018 . Accessed October 5, 2020 at: https://www.who.int/news-room/fact-sheets/detail/the-top-10-causes-of-death
- 2 Feigin VL, Norrving B, Mensah GA. Global burden of stroke. Circ Res 2017; 120 (03) 439-448
- 3 Andersen KK, Olsen TS, Dehlendorff C, Kammersgaard LP. Hemorrhagic and ischemic strokes compared: stroke severity, mortality, and risk factors. Stroke 2009; 40 (06) 2068-2072
- 4 Hart RG, Diener HC, Coutts SB. et al; Cryptogenic Stroke/ESUS International Working Group. Embolic strokes of undetermined source: the case for a new clinical construct. Lancet Neurol 2014; 13 (04) 429-438
- 5 Tomek A. Embolic stroke of undetermined source (ESUS). CNS 2018; 4: 92-97
- 6 Hart RG, Catanese L, Perera KS, Ntaios G, Connolly SJ. Embolic stroke of undetermined source: a systematic review and clinical update. Stroke 2017; 48 (04) 867-872
- 7 Kernan WN, Ovbiagele B, Black HR. et al; American Heart Association Stroke Council, Council on Cardiovascular and Stroke Nursing, Council on Clinical Cardiology, and Council on Peripheral Vascular Disease. 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 (07) 2160-2236
- 8 Albers GW, Amarenco P, Easton JD, Sacco RL, Teal P. Antithrombotic and thrombolytic therapy for ischemic stroke: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008; 133 (06) 630S-669S
- 9 Lansberg MG, O'Donnell MJ, Khatri P. et al. Antithrombotic and thrombolytic therapy for ischemic stroke: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141 (2, Suppl): e601S-e636S
- 10 Hart RG, Sharma M, Mundl H. et al; NAVIGATE ESUS Investigators. Rivaroxaban for stroke prevention after embolic stroke of undetermined source. N Engl J Med 2018; 378 (23) 2191-2201
- 11 Diener HC, Sacco RL, Easton JD. et al; RE-SPECT ESUS Steering Committee and Investigators. Dabigatran for prevention of stroke after embolic stroke of undetermined source. N Engl J Med 2019; 380 (20) 1906-1917
- 12 Topcuoglu MA, Liu L, Kim DE, Gurol ME. Updates on prevention of cardioembolic strokes. J Stroke 2018; 20 (02) 180-196
- 13 LaMori JC, Mody SH, Gross HJ. et al. Burden of comorbidities among patients with atrial fibrillation. Ther Adv Cardiovasc Dis 2013; 7 (02) 53-62
- 14 Wolf PA, Abbott RD, Kannel WB. Atrial fibrillation as an independent risk factor for stroke: the Framingham Study. Stroke 1991; 22 (08) 983-988
- 15 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 (38) 2893-2962
- 16 Steffel J, Verhamme P, Potpara TS. et al; ESC Scientific Document Group. 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 (16) 1330-1393
- 17 Adams Jr HP. Secondary prevention of atherothrombotic events after ischemic stroke. Mayo Clin Proc 2009; 84 (01) 43-51
- 18 Aboyans V, Ricco JB, Bartelink MEL. et al. Editor's Choice - 2017 ESC Guidelines on the Diagnosis and Treatment of Peripheral Arterial Diseases, in collaboration with the European Society for Vascular Surgery (ESVS). Eur J Vasc Endovasc Surg 2018; 55 (03) 305-368
- 19 Knuuti J, Wijns W, Saraste A. et al; ESC Scientific Document Group. 2019 ESC guidelines for the diagnosis and management of chronic coronary syndromes. Eur Heart J 2020; 41 (03) 407-477
- 20 Smith Jr SC, Benjamin EJ, Bonow RO. et al; World Heart Federation and the Preventive Cardiovascular Nurses Association. AHA/ACCF secondary prevention and risk reduction therapy for patients with coronary and other atherosclerotic vascular disease: 2011 update: a guideline from the American Heart Association and American College of Cardiology Foundation. Circulation 2011; 124 (22) 2458-2473
- 21 Roffi M, Patrono C, Collet JP. et al; ESC Scientific Document Group. 2015 ESC guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: Task Force for the Management of Acute Coronary Syndromes in Patients Presenting without Persistent ST-Segment Elevation of the European Society of Cardiology (ESC). Eur Heart J 2016; 37 (03) 267-315
- 22 Hurlen M, Abdelnoor M, Smith P, Erikssen J, Arnesen H. Warfarin, aspirin, or both after myocardial infarction. N Engl J Med 2002; 347 (13) 969-974
- 23 van Es RF, Jonker JJ, Verheugt FW, Deckers JW, Grobbee DE. Antithrombotics in the Secondary Prevention of Events in Coronary Thrombosis-2 (ASPECT-2) Research Group. Aspirin and coumadin after acute coronary syndromes (the ASPECT-2 study): a randomised controlled trial. Lancet 2002; 360 (9327): 109-113
- 24 Alexander JH, Lopes RD, James S. et al; APPRAISE-2 Investigators. Apixaban with antiplatelet therapy after acute coronary syndrome. N Engl J Med 2011; 365 (08) 699-708
- 25 Oldgren J, Budaj A, Granger CB. et al; RE-DEEM Investigators. Dabigatran vs. placebo in patients with acute coronary syndromes on dual antiplatelet therapy: a randomized, double-blind, phase II trial. Eur Heart J 2011; 32 (22) 2781-2789
- 26 Mega JL, Braunwald E, Wiviott SD. et al; ATLAS ACS 2–TIMI 51 Investigators. Rivaroxaban in patients with a recent acute coronary syndrome. N Engl J Med 2012; 366 (01) 9-19
- 27 Eikelboom JW, Connolly SJ, Bosch J. et al; COMPASS Investigators. Rivaroxaban with or without aspirin in stable cardiovascular disease. N Engl J Med 2017; 377 (14) 1319-1330
- 28 Go AS, Fang MC, Udaltsova N. et al; ATRIA Study Investigators. Impact of proteinuria and glomerular filtration rate on risk of thromboembolism in atrial fibrillation: the Anticoagulation and Risk Factors in Atrial Fibrillation (ATRIA) study. Circulation 2009; 119 (10) 1363-1369
- 29 Connolly SJ, Ezekowitz MD, Yusuf S. et al; RE-LY Steering Committee and Investigators. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 2009; 361 (12) 1139-1151
- 30 Patel MR, Mahaffey KW, Garg J. et al; ROCKET AF Investigators. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med 2011; 365 (10) 883-891
- 31 Granger CB, Alexander JH, McMurray JJ. et al; ARISTOTLE Committees and Investigators. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med 2011; 365 (11) 981-992
- 32 Giugliano RP, Ruff CT, Braunwald E. et al; ENGAGE AF-TIMI 48 Investigators. Edoxaban versus warfarin in patients with atrial fibrillation. N Engl J Med 2013; 369 (22) 2093-2104
- 33 Ruff CT, Giugliano RP, Braunwald E. et al. Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials. Lancet 2014; 383 (9921): 955-962
- 34 Coleman CI, Peacock WF, Bunz TJ, Alberts MJ. Effectiveness and safety of apixaban, dabigatran, and rivaroxaban versus warfarin in patients with nonvalvular atrial fibrillation and previous stroke or transient ischemic attack. Stroke 2017; 48 (08) 2142-2149
- 35 Camm AJ, Amarenco P, Haas S. et al; XANTUS Investigators. XANTUS: a real-world, prospective, observational study of patients treated with rivaroxaban for stroke prevention in atrial fibrillation. Eur Heart J 2016; 37 (14) 1145-1153
- 36 Coleman CI, Briere JB, Fauchier L. et al. Meta-analysis of real-world evidence comparing non-vitamin K antagonist oral anticoagulants with vitamin K antagonists for the treatment of patients with non-valvular atrial fibrillation. J Mark Access Health Policy 2019; 7 (01) 1574541
- 37 Ntaios G, Papavasileiou V, Makaritsis K, Vemmos K, Michel P, Lip GYH. Real-world setting comparison of non-vitamin-K antagonist oral anticoagulants versus vitamin-K antagonists for stroke prevention in atrial fibrillation: a systematic review and meta-analysis. Stroke 2017; 48 (09) 2494-2503
- 38 Yao X, Shah ND, Sangaralingham LR, Gersh BJ, Noseworthy PA. Non-vitamin K antagonist oral anticoagulant dosing in patients with atrial fibrillation and renal dysfunction. J Am Coll Cardiol 2017; 69 (23) 2779-2790
- 39 Kumar S, Lim E, Covic A. , et al. Anticoagulation in Concomitant Chronic Kidney Disease and Atrial Fibrillation: JACC Review Topic of the Week. J Am Coll Cardiol 2019; 74 (17) 2204-2215
- 40 Potpara TS, Ferro CJ, Lip GYH. Use of oral anticoagulants in patients with atrial fibrillation and renal dysfunction. Nat Rev Nephrol 2018; 14 (05) 337-351
- 41 Olesen JB, Lip GYH, Kamper AL. et al. Stroke and bleeding in atrial fibrillation with chronic kidney disease. N Engl J Med 2012; 367 (07) 625-635
- 42 Yao X, Tangri N, Gersh BJ. et al. Renal outcomes in anticoagulated patients with atrial fibrillation. J Am Coll Cardiol 2017; 70 (21) 2621-2632
- 43 Fox KAA, 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 (19) 2387-2394
- 44 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 (09) 961-970
- 45 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 (22) 2821-2830
- 46 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 (01) 24-36
- 47 Weir MR, Berger JS, Ashton V. et al. Impact of renal function on ischemic stroke and major bleeding rates in nonvalvular atrial fibrillation patients treated with warfarin or rivaroxaban: a retrospective cohort study using real-world evidence. Curr Med Res Opin 2017; 33 (10) 1891-1900
- 48 Coleman CI, Martinez BK, Turpie AGG, Sood N, Bunz TJ, Kreutz R. Effectiveness and safety of rivaroxaban vs. warfarin in patients with nonvalvular atrial fibrillation and moderate-to-severe chronic kidney disease. Blood 2017; 130: 2393
- 49 Bonnemeier H, Huelsebeck M, Kloss S. Comparative effectiveness of rivaroxaban versus a vitamin K antagonist in patients with renal impairment treated for non-valvular atrial fibrillation in Germany - a retrospective cohort study. Int J Cardiol Heart Vasc 2019; 23: 100367
- 50 Bonnemeier H, Kreutz R, Kloss S, Enders D, Häckl D, Schmedt N. Comparative safety and effectiveness of non-vitamin-K oral anticoagulants vs phenprocoumon in patients with non-valvular atrial fibrillation and renal disease - results from the RELOADED study. Paper presented at: 5th European Stroke Organisation Conference, Milan, Italy, May 22–24,2019. Abstract AS25–066. Accessed October 5, 2020 at: https://journals.sagepub.com/toc/esoa/4/1_suppl
- 51 Chan KE, Edelman ER, Wenger JB, Thadhani RI, Maddux FW. Dabigatran and rivaroxaban use in atrial fibrillation patients on hemodialysis. Circulation 2015; 131 (11) 972-979
- 52 Stanton BE, Barasch NS, Tellor KB. Comparison of the safety and effectiveness of apixaban versus warfarin in patients with severe renal impairment. Pharmacotherapy 2017; 37 (04) 412-419
- 53 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; 138 (15) 1519-1529
- 54 Coleman CI, Kreutz R, Sood NA. et al. Rivaroxaban versus warfarin in patients with nonvalvular atrial fibrillation and severe kidney disease or undergoing hemodialysis. Am J Med 2019; 132 (09) 1078-1083
- 55 Chang SH, Wu CV, Yeh YH. et al. Efficacy and safety of oral anticoagulants in patients with atrial fibrillation and stages 4 or 5 chronic kidney disease. Am J Med 2019; 132 (11) 1335-1343.e6
- 56 Marti HP, Serebruany V, Atar D. Challenging anticoagulation in advanced renal failure. Am J Med 2019; 132 (11) 1258-1259
- 57 Janssen Pharmaceuticals Inc., Xarelto (rivaroxaban): Prescribing Information. 2020 . Accessed October 5, 2020 at: http://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/XARELTO-pi.pdf
- 58 Boehringer Ingelheim Pharmaceuticals Inc., Pradaxa ® (dabigatran etexilate): Prescribing Information. 2020 . Accessed October 5, 2020 at: http://bidocs.boehringer-ingelheim.com/BIWebAccess/ViewServlet.ser?docBase=renetnt&folderPath=/Prescribing%20Information/PIs/Pradaxa/Pradaxa.pdf
- 59 Daiichi Sankyo Inc., Savaysa ® (edoxaban): Prescribing information. 2020 . Accessed October 5, 2020 at: http://dsi.com/prescribing-information-portlet/getPIContent?productName=Savaysa&inline=true
- 60 Bristol-Myers Squibb Company, Pfizer Inc. Eliquis ® (apixaban): Prescribing Information. 2019 . Accessed October 5, 2020 at: http://packageinserts.bms.com/pi/pi_eliquis.pdf
- 61 Pokorney SD. RENAL-AF: Apixaban vs. warfarin for stroke prevention in patients with end stage renal disease on hemodialysis and AFib. 2019 . Accessed February 4, 2020 at: https://www.acc.org/education-and-meetings/image-and-slide-gallery/media-detail?id=469e5bd88fff4d2bb8ec183e71521637
- 62 Atrial Fibrillation Network, Bristol-Myers Squibb, Pfizer, Compare apixaban and vitamin-K antagonists in patients with atrial fibrillation (AF) and end-stage kidney disease (ESKD) (AXADIA). 2019 . Accessed October 5, 2020 at: https://clinicaltrials.gov/ct2/show/NCT02933697
- 63 St Michael's Hospital, Canadian Institutes of Health Research, Strategies for the management of atrial fibrillation in patients receiving hemodialysis (SAFE-HD). 2019 . Accessed October 5, 2020 at: https://clinicaltrials.gov/ct2/show/NCT03987711
- 64 Wheeler DS, Giugliano RP, Rangaswami J. Anticoagulation-related nephropathy. J Thromb Haemost 2016; 14 (03) 461-467
- 65 Brodsky S, Eikelboom J, Hebert LA. Anticoagulant-related nephropathy. J Am Soc Nephrol 2018; 29 (12) 2787-2793
- 66 Posch F, Ay C, Stöger H, Kreutz R, Beyer-Westendorf J. Exposure to vitamin k antagonists and kidney function decline in patients with atrial fibrillation and chronic kidney disease. Res Pract Thromb Haemost 2019; 3 (02) 207-216
- 67 Peeters FECM, Dudink EAMP, Kimenai DM. et al. Vitamin K antagonists, non-vitamin K antagonist oral anticoagulants, and vascular calcification in patients with atrial fibrillation. TH Open 2018; 2 (04) e391-e398
- 68 Di Lullo L, Ronco C, Cozzolino M. et al. Non-vitamin K-dependent oral anticoagulants (NOACs) in chronic kidney disease patients with atrial fibrillation. Thromb Res 2017; 155: 38-47
- 69 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 (02) 181-189
- 70 Ryan M, Ware K, Qamri Z. et al. Warfarin-related nephropathy is the tip of the iceberg: direct thrombin inhibitor dabigatran induces glomerular hemorrhage with acute kidney injury in rats. Nephrol Dial Transplant 2014; 29 (12) 2228-2234
- 71 van Gorp RH, Schurgers LJ. New insights into the pros and cons of the clinical use of vitamin K antagonists (VKAs) versus direct oral anticoagulants (DOACs). Nutrients 2015; 7 (11) 9538-9557
- 72 de Aquino Moura KB, Behrens PMP, Pirolli R. et al. Anticoagulant-related nephropathy: systematic review and meta-analysis. Clin Kidney J 2019; 12 (03) 400-407
- 73 Brodsky SV, Mhaskar NS, Thiruveedi S. et al. Acute kidney injury aggravated by treatment initiation with apixaban: another twist of anticoagulant-related nephropathy. Kidney Res Clin Pract 2017; 36 (04) 387-392
- 74 Shin JI, Luo S, Alexander GC. et al. Direct oral anticoagulants and risk of acute kidney injury in patients with atrial fibrillation. J Am Coll Cardiol 2018; 71 (02) 251-252
- 75 Chan YH, Yeh YH, See LC. et al. Acute kidney injury in Asians with atrial fibrillation treated with dabigatran or warfarin. J Am Coll Cardiol 2016; 68 (21) 2272-2283
- 76 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: 83-89
- 77 Klil-Drori AJ, Azoulay L, Nie R, Renoux C, Nessim SJ, Filion KB. Comparative risk of acute kidney injury with oral anticoagulant use among patients with nonvalvular atrial fibrillation. Blood 2017; 130: 700
- 78 Coleman CI, Kreutz R, Sood N. et al. Rivaroxaban's impact on renal decline in patients with nonvalvular atrial fibrillation: a US MarketScan claims database analysis. Clin Appl Thromb Hemost 2019; 25 DOI: 1076029619868535.
- 79 Bonnemeier H, Kreutz R, Kloss S, Enders D, Häckl D, Schmedt N. Comparative safety and effectiveness of non-vitamin-K oral anticoagulants vs phenprocoumon in patients with non-valvular atrial fibrillation and diabetes - results from the RELOADED study. Paper presented at: 5th European Stroke Organisation Conference. Milan, Italy, 22-24 May 2019, AS25-069. Accessed October 5, 2020 at: https://journals.sagepub.com/toc/esoa/4/1_suppl
- 80 Vaitsiakhovich T, Coleman CI, Kleinjung F. et al. Worsening of renal function in atrial fibrillation patients with stage 3 or 4 chronic kidney disease treated with warfarin or rivaroxaban - evidence from the real-world CALLIPER study in the US claims. European Society of Cardiology Congress. Paris, France, 31 August–5 September 2019, Poster P4746. Accessed October 5, 2020 at: https://academic.oup.com/eurheartj/article-abstract/40/Supplement_1/ehz745.1122/5596296?redirectedFrom=fulltext
- 81 Hernandez AV, Bradley G, Khan M. et al. Rivaroxaban vs. warfarin and renal outcomes in non-valvular atrial fibrillation patients with diabetes. Eur Heart J Qual Care Clin Outcomes 2020; 6 (04) 301-307
- 82 GWT-TUD GmbH, ClinStat GmbH, Factor XA - inhibition in renal patients with non-valvular atrial fibrillation - observational registry (XARENO). 2019 . Accessed October 5, 2020 at: https://clinicaltrials.gov/ct2/show/NCT02663076
- 83 January CT, Wann LS, Calkins H. et al. 2019 AHA/ACC/HRS Focused Update of the 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 Clinical Practice Guidelines and the Heart Rhythm Society in collaboration with the Society of Thoracic Surgeons. Circulation 2019; 140 (02) e125-e151
- 84 De Sensi F, De Potter T, Cresti A, Severi S, Breithardt G. Atrial fibrillation in patients with diabetes: molecular mechanisms and therapeutic perspectives. Cardiovasc Diagn Ther 2015; 5 (05) 364-373
- 85 Bhatt DL, Steg PG, Ohman EM. et al; REACH Registry Investigators. International prevalence, recognition, and treatment of cardiovascular risk factors in outpatients with atherothrombosis. JAMA 2006; 295 (02) 180-189
- 86 Stroke Risk in Atrial Fibrillation Working Group. Independent predictors of stroke in patients with atrial fibrillation: a systematic review. Neurology 2007; 69 (06) 546-554
- 87 Olesen JB, Fauchier L, Lane DA, Taillandier S, Lip GYH. Risk factors for stroke and thromboembolism in relation to age among patients with atrial fibrillation: the Loire Valley Atrial Fibrillation Project. Chest 2012; 141 (01) 147-153
- 88 Fangel MV, Nielsen PB, Larsen TB. et al. Type 1 versus type 2 diabetes and thromboembolic risk in patients with atrial fibrillation: a Danish nationwide cohort study. Int J Cardiol 2018; 268: 137-142
- 89 Plitt A, McGuire DK, Giugliano RP. Atrial fibrillation, type 2 diabetes, and non-vitamin K antagonist oral anticoagulants: a review. JAMA Cardiol 2017; 2 (04) 442-448
- 90 Wang A, Green JB, Halperin JL, Piccini Sr JP. Atrial fibrillation and diabetes mellitus: JACC review topic of the week. J Am Coll Cardiol 2019; 74 (08) 1107-1115
- 91 American Diabetes Association. 10. Cardiovascular disease and risk management: standards of medical care in diabetes—2019. Diabetes Care 2019; 42 (Suppl. 01) S103-S123
- 92 Koye DN, Magliano DJ, Nelson RG, Pavkov ME. The global epidemiology of diabetes and kidney disease. Adv Chronic Kidney Dis 2018; 25 (02) 121-132
- 93 Cavanaugh KL. Diabetes management issues for patients with chronic kidney disease. Clin Diabetes 2007; 25: 90-97
- 94 Coresh J, Astor BC, Greene T, Eknoyan G, Levey AS. Prevalence of chronic kidney disease and decreased kidney function in the adult US population: Third National Health and Nutrition Examination Survey. Am J Kidney Dis 2003; 41 (01) 1-12
- 95 Middleton RJ, Foley RN, Hegarty J. et al. The unrecognized prevalence of chronic kidney disease in diabetes. Nephrol Dial Transplant 2006; 21 (01) 88-92
- 96 Hertig A, Rondeau E. Role of the coagulation/fibrinolysis system in fibrin-associated glomerular injury. J Am Soc Nephrol 2004; 15 (04) 844-853
- 97 Farquhar A, MacDonald MK, Ireland JT. The role of fibrin deposition in diabetic glomerulosclerosis: a light, electron and immunofluorescence microscopy study. J Clin Pathol 1972; 25 (08) 657-667
- 98 Tanaka M, Arai H, Liu N. et al. Role of coagulation factor Xa and protease-activated receptor 2 in human mesangial cell proliferation. Kidney Int 2005; 67 (06) 2123-2133
- 99 Sumi A, Yamanaka-Hanada N, Bai F, Makino T, Mizukami H, Ono T. Roles of coagulation pathway and factor Xa in the progression of diabetic nephropathy in db/db mice. Biol Pharm Bull 2011; 34 (06) 824-830
- 100 Amdur RL, Feldman HI, Gupta J. et al; CRIC Study Investigators. Inflammation and progression of CKD: the CRIC study. Clin J Am Soc Nephrol 2016; 11 (09) 1546-1556
- 101 Afkarian M, Sachs MC, Kestenbaum B. et al. Kidney disease and increased mortality risk in type 2 diabetes. J Am Soc Nephrol 2013; 24 (02) 302-308
- 102 Ezekowitz JA, Lewis BS, Lopes RD. et al. Clinical outcomes of patients with diabetes and atrial fibrillation treated with apixaban: results from the ARISTOTLE trial. Eur Heart J Cardiovasc Pharmacother 2015; 1 (02) 86-94
- 103 Brambatti M, Darius H, Oldgren J. et al. Comparison of dabigatran versus warfarin in diabetic patients with atrial fibrillation: Results from the RE-LY trial. Int J Cardiol 2015; 196: 127-131
- 104 Bansilal S, Bloomgarden Z, Halperin JL. et al; ROCKET AF Steering Committee and Investigators. Efficacy and safety of rivaroxaban in patients with diabetes and nonvalvular atrial fibrillation: 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 Trial). Am Heart J 2015; 170 (04) 675.e8-682.e8
- 105 Plitt A, Ruff CT, Goudev A. et al. Efficacy and safety of edoxaban in patients with diabetes mellitus in the ENGAGE AF-TIMI 48 trial. Int J Cardiol 2020; 304: 185-191
- 106 Coleman CI, Bunz TJ, Eriksson D, Meinecke AK, Sood NA. Effectiveness and safety of rivaroxaban vs warfarin in people with non-valvular atrial fibrillation and diabetes: an administrative claims database analysis. Diabet Med 2018; 35 (08) 1105-1110
- 107 Baker WL, Beyer-Westendorf J, Bunz TJ. et al. Effectiveness and safety of rivaroxaban and warfarin for prevention of major adverse cardiovascular or limb events in patients with non-valvular atrial fibrillation and type 2 diabetes. Diabetes Obes Metab 2019; 21 (09) 2107-2114
- 108 Bayer AG. Xarelto ® (rivaroxaban): summary of product characteristics. 2020 . Accessed July 30, 2020 at: https://www.ema.europa.eu/documents/product-information/xarelto-epar-product-information_en.pdf
- 109 Bristol Myers Squibb, Pfizer, Eliquis® (apixaban): summary of product characteristics. 2020 . Accessed July 30, 2020 at: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002148/WC500107728.pdf
- 110 Boehringer Ingelheim International GmbH, Pradaxa® (dabigatran etexilate): summary of product characteristics. 2020 . Accessed September 8, 2020 at: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000829/WC500041059.pdf
- 111 Daiichi Sankyo Europe Gmb H. Lixiana® (edoxaban): summary of product characteristics. 2019 . Accessed April 9, 2020 at: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002629/WC500189045.pdf
- 112 Steinberg BA, Shrader P, Thomas L. et al; ORBIT-AF Investigators and Patients. Off-label dosing of non-vitamin K antagonist oral anticoagulants and adverse outcomes: the ORBIT-AF II registry. J Am Coll Cardiol 2016; 68 (24) 2597-2604
- 113 Steinberg BA, Shrader P, Pieper K. et al; Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT, ‐AF) II Investigators. Frequency and outcomes of reduced dose non-vitamin K antagonist anticoagulants: results from ORBIT-AF II (The Outcomes Registry for Better Informed Treatment of Atrial Fibrillation II). J Am Heart Assoc 2018; 7 (04) e007633
- 114 Atar D, Grundvold I. On-label reduced doses of non-vitamin K anticoagulants prove safe and efficient; yet how to ensure the correct dose for the right patient?. Eur Heart J 2019; 40 (19) 1501-1503
- 115 Lowres N, Giskes K, Hespe C, Freedman B. Reducing stroke risk in atrial fibrillation: adherence to guidelines has improved, but patient persistence with anticoagulant therapy remains suboptimal. Korean Circ J 2019; 49 (10) 883-907
- 116 Geisler T, Poli S, Meisner C. et al. Apixaban for treatment of embolic stroke of undetermined source (ATTICUS randomized trial): rationale and study design. Int J Stroke 2017; 12 (09) 985-990
- 117 Kamel H, Longstreth Jr WT, Tirschwell DL. et al. The AtRial Cardiopathy and Antithrombotic Drugs In prevention After cryptogenic stroke randomized trial: rationale and methods. Int J Stroke 2019; 14 (02) 207-214
- 118 Healey JS, Gladstone DJ, Swaminathan B. et al. Recurrent stroke with rivaroxaban compared with aspirin according to predictors of atrial fibrillation: secondary analysis of the NAVIGATE ESUS randomized clinical trial. JAMA Neurol 2019; 76 (07) 764-773
- 119 Ntaios G, Perlepe K, Lambrou D. et al. Prevalence and overlap of potential embolic sources in patients with embolic stroke of undetermined source. J Am Heart Assoc 2019; 8 (15) e012858
- 120 University of Thessaly, University of Lausanne, University of Athens, Prediction of AF in ESUS (AF-ESUS). 2019 . Accessed October 5, 2020 at: https://clinicaltrials.gov/ct2/show/NCT02766205
- 121 University of British Columbia, Boehringer Ingelheim, Thirty day heart monitoring for detection of atrial fibrillation among cryptogenic stroke patients (PROPhecy). 2019 . Accessed October 5, 2020 at: https://clinicaltrials.gov/ct2/show/NCT03712865
- 122 Ntaios G. Embolic stroke of undetermined source: JACC review topic of the week. J Am Coll Cardiol 2020; 75 (03) 333-340
- 123 Sharma M, Hart RG, Connolly SJ. et al. Stroke outcomes in the COMPASS trial. Circulation 2019; 139 (09) 1134-1145
- 124 Alexander JH, Becker RC, Bhatt DL. et al; APPRAISE Steering Committee and Investigators. Apixaban, an oral, direct, selective factor Xa inhibitor, in combination with antiplatelet therapy after acute coronary syndrome: results of the Apixaban for Prevention of Acute Ischemic and Safety Events (APPRAISE) trial. Circulation 2009; 119 (22) 2877-2885
- 125 Perera KS, Ng KKH, Nayar S. et al. Association between low-dose rivaroxaban with or without aspirin and ischemic stroke subtypes: a secondary analysis of the COMPASS trial. JAMA Neurol 2020; 77 (01) 43-48
- 126 Ferreira JP, Girerd N, Gregson J. et al; High-Risk Myocardial Infarction Database Initiative. Stroke risk in patients with reduced ejection fraction after myocardial infarction without atrial fibrillation. J Am Coll Cardiol 2018; 71 (07) 727-735
- 127 Melgaard L, Gorst-Rasmussen A, Lane DA, Rasmussen LH, Larsen TB, Lip GYH. Assessment of the CHA2DS2-VASc score in predicting ischemic stroke, thromboembolism, and death in patients with heart failure with and without atrial fibrillation. JAMA 2015; 314 (10) 1030-1038
- 128 Zannad F, Anker SD, Byra WM. et al; COMMANDER HF Investigators. Rivaroxaban in patients with heart failure, sinus rhythm, and coronary disease. N Engl J Med 2018; 379 (14) 1332-1342
- 129 Mehra MR, Vaduganathan M, Fu M. et al. A comprehensive analysis of the effects of rivaroxaban on stroke or transient ischaemic attack in patients with heart failure, coronary artery disease, and sinus rhythm: the COMMANDER HF trial. Eur Heart J 2019; 40 (44) 3593-3602