Cardiovasc Prev Pharmacother.  2020 Jan;2(1):1-10. 10.36011/cpp.2020.2.e5.

Dose Selection of Non-Vitamin K Antagonist Oral Anticoagulants in Korean Patients with Non-Valvular Atrial Fibrillation

Affiliations
  • 1Division of cardiology, Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea
  • 2Division of Cardiology, Department of Internal Medicine, Heart Vascular Stroke Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea

Abstract

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia. In the Asian population, patients with AF have been shown to have increased risks of ischemic stroke and all-cause death compared to patients without AF by 3.34- and 2.61-fold, respectively. AF guidelines recommend oral anticoagulation (OAC) therapy in AF patients with a CHA2DS2-VASc score of ≥1 for men and ≥2 for women with non-valvular AF. After the introduction of non-vitamin K antagonist oral anticoagulants (NOACs) as a treatment for AF, their use has become widespread. Compared to warfarin, NOACs showed comparable efficacy for the prevention of thromboembolic events and superior safety in terms of bleeding complications, especially intracranial hemorrhage. Physicians should keep in mind considerations for optimal OAC therapy to achieve the best outcome. Furthermore, appropriate dose selection in order to achieve the best clinical outcome is an important issue in clinical practice. All NOACs do not have the same rules for dose reduction, and dose reduction of NOACs is primarily recommended according to the dose reduction criteria investigated in pivotal randomized control trials. In this review, we focus on the optimal dose of NOAC and summarize current guidelines and evidence for appropriate dosing of NOACs.

Keyword

Atrial fibrillation; Stroke; Anticoagulants; Factor Xa inhibitors

Reference

1. Lee SR, Choi EK, Han KD, Cha MJ, Oh S. Trends in the incidence and prevalence of atrial fibrillation and estimated thromboembolic risk using the CHA2DS2-VASc score in the entire Korean population. Int J Cardiol. 2017; 236:226–31.
2. Rahman F, Kwan GF, Benjamin EJ. Global epidemiology of atrial fibrillation. Nat Rev Cardiol. 2016; 13:501.
Article
3. Kim D, Yang PS, Jang E, Yu HT, Kim TH, Uhm JS, Kim JY, Pak HN, Lee MH, Joung B, Lip GY. Increasing trends in hospital care burden of atrial fibrillation in Korea, 2006 through 2015. Heart. 2018; 104:2010–7.
Article
4. Chao TF, Liu CJ, Tuan TC, Chen TJ, Hsieh MH, Lip GY, Chen SA. Lifetime risks, projected numbers, and adverse outcomes in Asian patients with atrial fibrillation: a report from the Taiwan Nationwide AF Cohort Study. Chest. 2018; 153:453–66.
Article
5. Kirchhof P, Benussi S, Kotecha D, Ahlsson A, Atar D, Casadei B, Castella M, Diener HC, Heidbuchel H, Hendriks J, Hindricks G, Manolis AS, Oldgren J, Popescu BA, Schotten U, Van Putte B, Vardas P; 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.
Article
6. January CT, Wann LS, Calkins H, Chen LY, Cigarroa JE, Cleveland JC Jr, Ellinor PT, Ezekowitz MD, Field ME, Furie KL, Heidenreich PA, Murray KT, Shea JB, Tracy CM, Yancy CW. 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. J Am Coll Cardiol. 2019; 74:104–32.
7. Lip GY, Banerjee A, Boriani G, Chiang CE, Fargo R, Freedman B, Lane DA, Ruff CT, Turakhia M, Werring D, Patel S, Moores L. Antithrombotic therapy for atrial fibrillation: CHEST guideline and expert panel report. Chest. 2018; 154:1121–201.
8. Joung B, Lee JM, Lee KH, Kim TH, Choi EK, Lim WH, Kang KW, Shim J, Lim HE, Park J, Lee SR, Lee YS, Kim JB; KHRS Atrial Fibrillation Guideline Working Group. 2018 Korean guideline of atrial fibrillation management. Korean Circ J. 2018; 48:1033–80.
Article
9. Ruff CT, Giugliano RP, Braunwald E, Hoffman EB, Deenadayalu N, Ezekowitz MD, Camm AJ, Weitz JI, Lewis BS, Parkhomenko A, Yamashita T, Antman EM. 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; 383:955–62.
Article
10. Huisman MV, Rothman KJ, Paquette M, Teutsch C, Diener HC, Dubner SJ, Halperin JL, Ma CS, Zint K, Elsaesser A, Bartels DB, Lip GY; GLORIA-AF Investigators. The changing landscape for stroke prevention in af: findings from the GLORIA-AF Registry Phase 2. J Am Coll Cardiol. 2017; 69:777–85.
11. Camm AJ, Accetta G, Ambrosio G, Atar D, Bassand JP, Berge E, Cools F, Fitzmaurice DA, Goldhaber SZ, Goto S, Haas S, Kayani G, Koretsune Y, Mantovani LG, Misselwitz F, Oh S, Turpie AG, Verheugt FW, Kakkar AK; GARFIELD-AF Investigators. Evolving antithrombotic treatment patterns for patients with newly diagnosed atrial fibrillation. Heart. 2017; 103:307–14.
Article
12. Lee SR, Choi EK, Han KD, Cha MJ, Oh S, Lip GY. Temporal trends of antithrombotic therapy for stroke prevention in Korean patients with non-valvular atrial fibrillation in the era of non-vitamin K antagonist oral anticoagulants: a nationwide population-based study. PLoS One. 2017; 12:e0189495.
Article
13. Chao TF, Chiang CE, Lin YJ, Chang SL, Lo LW, Hu YF, Tuan TC, Liao JN, Chung FP, Chen TJ, Lip GY, Chen SA. Evolving changes of the use of oral anticoagulants and outcomes in patients with newly diagnosed atrial fibrillation in Taiwan. Circulation. 2018; 138:1485–7.
Article
14. Steffel J, Verhamme P, Potpara TS, Albaladejo P, Antz M, Desteghe L, Haeusler KG, Oldgren J, Reinecke H, Roldan-Schilling V, Rowell N, Sinnaeve P, Collins R, Camm AJ, Heidbüchel H; 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; 39:1330–93.
15. Connolly SJ, Ezekowitz MD, Yusuf S, Eikelboom J, Oldgren J, Parekh A, Pogue J, Reilly PA, Themeles E, Varrone J, Wang S, Alings M, Xavier D, Zhu J, Diaz R, Lewis BS, Darius H, Diener HC, Joyner CD, Wallentin L; RE-LY Steering Committee and Investigators. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009; 361:1139–51.
Article
16. Patel MR, Mahaffey KW, Garg J, Pan G, Singer DE, Hacke W, Breithardt G, Halperin JL, Hankey GJ, Piccini JP, Becker RC, Nessel CC, Paolini JF, Berkowitz SD, Fox KA, Califf RM; ROCKET AF Investigators. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med. 2011; 365:883–91.
Article
17. Granger CB, Alexander JH, McMurray JJ, Lopes RD, Hylek EM, Hanna M, Al-Khalidi HR, Ansell J, Atar D, Avezum A, Bahit MC, Diaz R, Easton JD, Ezekowitz JA, Flaker G, Garcia D, Geraldes M, Gersh BJ, Golitsyn S, Goto S, Hermosillo AG, Hohnloser SH, Horowitz J, Mohan P, Jansky P, Lewis BS, Lopez-Sendon JL, Pais P, Parkhomenko A, Verheugt FW, Zhu J, Wallentin L; ARISTOTLE Committees and Investigators. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2011; 365:981–92.
Article
18. Giugliano RP, Ruff CT, Braunwald E, Murphy SA, Wiviott SD, Halperin JL, Waldo AL, Ezekowitz MD, Weitz JI, Špinar J, Ruzyllo W, Ruda M, Koretsune Y, Betcher J, Shi M, Grip LT, Patel SP, Patel I, Hanyok JJ, Mercuri M, Antman EM; ENGAGE AF-TIMI 48 Investigators. Edoxaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2013; 369:2093–104.
Article
19. Eikelboom JW, Wallentin L, Connolly SJ, Ezekowitz M, Healey JS, Oldgren J, Yang S, Alings M, Kaatz S, Hohnloser SH, Diener HC, Franzosi MG, Huber K, Reilly P, Varrone J, Yusuf S. Risk of bleeding with 2 doses of dabigatran compared with warfarin in older and younger patients with atrial fibrillation: an analysis of the randomized evaluation of long-term anticoagulant therapy (RE-LY) trial. Circulation. 2011; 123:2363–72.
Article
20. Steinberg BA, Shrader P, Thomas L, Ansell J, Fonarow GC, Gersh BJ, Kowey PR, Mahaffey KW, Naccarelli G, Reiffel J, Singer DE, Peterson ED, Piccini JP; 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; 68:2597–604.
21. Steinberg BA, Shrader P, Pieper K, Thomas L, Allen LA, Ansell J, Chan PS, Ezekowitz MD, Fonarow GC, Freeman JV, Gersh BJ, Kowey PR, Mahaffey KW, Naccarelli GV, Reiffel JA, Singer DE, Peterson ED, Piccini JP; 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 ORBITAF II (The Outcomes Registry for Better Informed Treatment of Atrial Fibrillation II). J Am Heart Assoc. 2018; 7:e007633.
Article
22. Chan YH, Kuo CT, Yeh YH, Chang SH, Wu LS, Lee HF, Tu HT, See LC. Thromboembolic, bleeding, and mortality risks of rivaroxaban and dabigatran in Asians with nonvalvular atrial fibrillation. J Am Coll Cardiol. 2016; 68:1389–401.
23. Cha MJ, Choi EK, Han KD, Lee SR, Lim WH, Oh S, Lip GY. Effectiveness and safety of non-vitamin K antagonist oral anticoagulants in Asian patients with atrial fibrillation. Stroke. 2017; 48:3040–8.
Article
24. Lee SR, Choi EK, Han KD, Jung JH, Oh S, Lip GY. Edoxaban in Asian patients with atrial fibrillation: effectiveness and safety. J Am Coll Cardiol. 2018; 72:838–53.
25. Yu HT, Yang PS, Kim TH, Jang E, Kim D, Uhm JS, Kim JY, Pak HN, Lee MH, Lip GY, Joung B. Impact of Renal Function on Outcomes With Edoxaban in Real-World Patients With Atrial Fibrillation. Stroke. 2018; 49:2421–9.
Article
26. Lee SR, Choi EK, Han KD, Jung JH, Oh S, Lip GY. Optimal rivaroxaban dose in Asian patients with atrial fibrillation and normal or mildly impaired renal function. Stroke. 2019; 50:1140–8.
Article
27. Lee SR, Choi EK, Han KD, Jung JH, Cha MJ, Oh S, Lip GYH. Non-vitamin K antagonist oral anticoagulants in Asian patients with supranormal renal function. Stroke. 2019; 50:1480–9.
Article
28. Lee SR, Choi EK, Park CS, Han KD, Jung JH, Oh S, Lip GY. Direct oral anticoagulants in patients with nonvalvular atrial fibrillation and low body weight. J Am Coll Cardiol. 2019; 73:919–31.
29. Cho MS, Yun JE, Park JJ, Kim YJ, Lee J, Kim H, Park DW, Nam GB. Outcomes after use of standard- and low-dose non-vitamin K oral anticoagulants in Asian patients with atrial fibrillation. Stroke. 2019; 50:110–8.
Article
30. Chan YH, Lee HF, See LC, Tu HT, Chao TF, Yeh YH, Wu LS, Kuo CT, Chang SH, Lip GY. Effectiveness and safety of four direct oral anticoagulants in Asian patients with nonvalvular atrial fibrillation. Chest. 2019; 156:529–43.
Article
31. Lee SR, Choi EK, Kwon S, Han KD, Jung JH, Cha MJ, Oh S, Lip GY. Effectiveness and safety of contemporary oral anticoagulants among Asians with nonvalvular atrial fibrillation. Stroke. 2019; 50:2245–9.
Article
32. Lee SR, Choi EK, Kwon S, Jung JH, Han KD, Cha MJ, Oh S, Lip GY. Oral anticoagulation in Asian patients with atrial fibrillation and a history of intracranial hemorrhage. Stroke. 2020; 51:416–23.
Article
33. Park J, Lee SR, Choi EK, Kwon S, Jung JH, Han KD, Cha MJ, Ko SB, Oh S, Lip GY. Effectiveness and safety of direct oral anticoagulant for secondary prevention in Asians with atrial fibrillation. J Clin Med. 2019; 8:E2228.
Article
34. Larsen TB, Skjøth F, Nielsen PB, Kjældgaard JN, Lip GY. Comparative effectiveness and safety of nonvitamin K antagonist oral anticoagulants and warfarin in patients with atrial fibrillation: propensity weighted nationwide cohort study. BMJ. 2016; 353:i3189.
Article
35. Nielsen PB, Skjøth F, Søgaard M, Kjældgaard JN, Lip GY, Larsen TB. Effectiveness and safety of reduced dose non-vitamin K antagonist oral anticoagulants and warfarin in patients with atrial fibrillation: propensity weighted nationwide cohort study. BMJ. 2017; 356:j510.
Article
36. Noseworthy PA, Yao X, Abraham NS, Sangaralingham LR, McBane RD, Shah ND. Direct comparison of dabigatran, rivaroxaban, and apixaban for effectiveness and safety in nonvalvular atrial fibrillation. Chest. 2016; 150:1302–12.
Article
37. Lip GY, Keshishian A, Li X, Hamilton M, Masseria C, Gupta K, Luo X, Mardekian J, Friend K, Nadkarni A, Pan X, Baser O, Deitelzweig S. Effectiveness and safety of oral anticoagulants among nonvalvular atrial fibrillation patients. Stroke. 2018; 49:2933–44.
Article
38. Blin P, Fauchier L, Dureau-Pournin C, Sacher F, Dallongeville J, Bernard MA, Lassalle R, Droz-Perroteau C, Moore N. Effectiveness and safety of rivaroxaban 15 or 20 mg versus vitamin K antagonists in nonvalvular atrial fibrillation. Stroke. 2019; 50:2469–76.
Article
39. Shen AY, Yao JF, Brar SS, Jorgensen MB, Chen W. Racial/ethnic differences in the risk of intracranial hemorrhage among patients with atrial fibrillation. J Am Coll Cardiol. 2007; 50:309–15.
Article
40. Hori M, Matsumoto M, Tanahashi N, Momomura S, Uchiyama S, Goto S, Izumi T, Koretsune Y, Kajikawa M, Kato M, Ueda H, Iwamoto K, Tajiri M; J-ROCKET AF study investigators. Rivaroxaban vs. warfarin in Japanese patients with atrial fibrillation - the J-ROCKET AF study -. Circ J. 2012; 76:2104–11.
Article
41. Lin YC, Chien SC, Hsieh YC, Shih CM, Lin FY, Tsao NW, Chen CW, Kao YT, Chiang KH, Chen WT, Chien LN, Huang CY. Effectiveness and safety of standard- and low-dose rivaroxaban in Asians with atrial fibrillation. J Am Coll Cardiol. 2018; 72:477–85.
42. Lee SR, Lee YS, Park JS, Cha MJ, Kim TH, Park J, Park JK, Lee JM, Kang KW, Shim J, Uhm JS, Kim J, Kim C, Kim JB, Park HW, Joung B, Choi EK. Label adherence for non-vitamin K antagonist oral anticoagulants in a prospective cohort of Asian patients with atrial fibrillation. Yonsei Med J. 2019; 60:277–84.
Article
43. Wallentin L, Yusuf S, Ezekowitz MD, Alings M, Flather M, Franzosi MG, Pais P, Dans A, Eikelboom J, Oldgren J, Pogue J, Reilly PA, Yang S, Connolly SJ; RE-LY investigators. Efficacy and safety of dabigatran compared with warfarin at different levels of international normalised ratio control for stroke prevention in atrial fibrillation: an analysis of the RE-LY trial. Lancet. 2010; 376:975–83.
Article
44. Wang KL, Lopes RD, Patel MR, Büller HR, Tan DS, Chiang CE, Giugliano RP. Efficacy and safety of reduced-dose non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation: a metaanalysis of randomized controlled trials. Eur Heart J. 2019; 40:1492–500.
Article
45. 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; 69:2779–90.
Article
46. Jung YH, Choi HY, Lee KY, Cheon K, Han SW, Park JH, Cho HJ, Park HJ, Nam HS, Heo JH, Lee HS, Kim YD. Stroke severity in patients on non-vitamin K antagonist oral anticoagulants with a standard or insufficient dose. Thromb Haemost. 2018; 118:2145–51.
Article
47. ClinicalTrials.gov. Safety and effectiveness of low dose edoxaban in patients with NVAF (LEDIOS) [Internet]. Bethesda, MD: U.S. National Library of Medicine; 2018 [cited 2019]. Available from https://www.clinicaltrials.gov/ct2/show/NCT03554837?term=LEDIOS&draw=2&rank=1.
48. ClinicalTrials.gov. Rivaroxaban in elderly NVAF patients with or without renal impairment (XAIENT) [Internet]. Bethesda, MD: U.S. National Library of Medicine; 2018 [cited 2019]. Available from https://www.clinicaltrials.gov/ct2/show/NCT04096547?term=XAIENT&draw=2&rank=1.
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