Direct comparison of non-vitamin K antagonist oral anticoagulant versus warfarin for stroke prevention in non-valvular atrial fibrillation: a systematic review and meta-analysis of real-world evidences

Springer Science and Business Media LLC - Tập 73 - Trang 1-17 - 2021
Yoga Waranugraha1, Ardian Rizal1, Mokhamad Fahmi Rizki Syaban2, Icha Farihah Deniyati Faratisha2, Nabila Erina Erwan2, Khadijah Cahya Yunita2
1Department of Cardiology and Vascular Medicine, Faculty of Medicine, Universitas Brawijaya, Malang, Indonesia
2Faculty of Medicine, Universitas Brawijaya, Malang, Indonesia

Tóm tắt

To overcome the several drawbacks of warfarin, non-vitamin K antagonist oral anticoagulants (NOACs) were developed. Even though randomized controlled trials (RCTs) provided high-quality evidence, the real-world evidence is still needed. This systematic review and meta-analysis proposed to measure the safety and efficacy profile between warfarin and NOACs in non-valvular atrial fibrillation (NVAF) patients in preventing stroke. We collected articles about the real-world studies comparing warfarin and NOACs for NVAF patients recorded in electronic scientific databases such as Embase, ProQuest, PubMed, and Cochrane. The pooled hazard ratio (HR) and 95% confidence interval (CI) were estimated using the generic inverse variance method. A total of 34 real-world studies, including 2287288 NVAF patients, were involved in this study. NOACs effectively reduced the stroke risk than warfarin (HR 0.77; 95% CI 0.69 to 0.87; p < 0.01). Moreover, NOACs effectively lowered all-cause mortality risk (HR 0.71; 95% CI 0.63 to 0.81; p < 0.01). From the safety aspect, compared to warfarin, NOACs significantly reduced major bleeding risk (HR 0.68; 95% CI 0.54 to 0.86; p < 0.01) and intracranial bleeding risk (HR 0.54; 95% CI 0.42 to 0.70; p < 0.01). However, NOACs administration failed to decrease gastrointestinal bleeding risk (HR 0.78; 95% CI 0.58 to 1.06; p = 0.12). In NVAF patients, NOACs were found to be more effective than warfarin at reducing stroke risk. NOACSs also lowered the risk of all-cause mortality, cerebral hemorrhage, and severe bleeding in NVAF patients compared to warfarin.

Tài liệu tham khảo

Ceornodolea AD, Bal R, Severens JL (2017) Epidemiology and management of atrial fibrillation and stroke: review of data from four European countries. Stroke Res Treat 2017:1–12. https://doi.org/10.1155/2017/8593207 Pistoia F, Sacco S, Tiseo C, Degan D, Ornello R, Carolei A (2016) The epidemiology of atrial fibrillation and stroke. Cardiol Clin 34(2):255–268. https://doi.org/10.1016/j.ccl.2015.12.002 Brieger D, Amerena J, Attia J, Bajorek B, Chan KH, Connell C, Freedman B, Ferguson C, Hall T, Haqqani H, Hendriks J, Hespe C, Hung J, Kalman JM, Sanders P, Worthington J, Yan TD, Zwar N (2018) National Heart Foundation of Australia and the Cardiac Society of Australia and New Zealand: Australian Clinical Guidelines for the Diagnosis and Management of Atrial Fibrillation 2018. Heart Lung Circ 27(10):1209–1266. https://doi.org/10.1016/j.hlc.2018.06.1043 Chiang C-E, Okumura K, Zhang S, Chao TF, Siu CW, Wei Lim T, Saxena A, Takahashi Y, Siong Teo W (2017) 2017 consensus of the Asia Pacific Heart Rhythm Society on stroke prevention in atrial fibrillation. J Arrhythmia 33(4):345–367. https://doi.org/10.1016/j.joa.2017.05.004 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) 2019 AHA/ACC/HRS focused update of the 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation. J Am Coll Cardiol 74(1):104–132. https://doi.org/10.1016/j.jacc.2019.01.011 Hindricks G, Potpara T, Dagres N, Arbelo E, Bax JJ, Blomström-Lundqvist C, Boriani G, Castella M, Dan GA, Dilaveris PE, Fauchier L, Filippatos G, Kalman JM, la Meir M, Lane DA, Lebeau JP, Lettino M, Lip GYH, Pinto FJ, Thomas GN, Valgimigli M, van Gelder IC, van Putte BP, Watkins CL, ESC Scientific Document Group, Kirchhof P, Kühne M, Aboyans V, Ahlsson A, Balsam P, Bauersachs J, Benussi S, Brandes A, Braunschweig F, Camm AJ, Capodanno D, Casadei B, Conen D, Crijns HJGM, Delgado V, Dobrev D, Drexel H, Eckardt L, Fitzsimons D, Folliguet T, Gale CP, Gorenek B, Haeusler KG, Heidbuchel H, Iung B, Katus HA, Kotecha D, Landmesser U, Leclercq C, Lewis BS, Mascherbauer J, Merino JL, Merkely B, Mont L, Mueller C, Nagy KV, Oldgren J, Pavlović N, Pedretti RFE, Petersen SE, Piccini JP, Popescu BA, Pürerfellner H, Richter DJ, Roffi M, Rubboli A, Scherr D, Schnabel RB, Simpson IA, Shlyakhto E, Sinner MF, Steffel J, Sousa-Uva M, Suwalski P, Svetlosak M, Touyz RM, Dagres N, Arbelo E, Bax JJ, Blomström-Lundqvist C, Boriani G, Castella M, Dan GA, Dilaveris PE, Fauchier L, Filippatos G, Kalman JM, la Meir M, Lane DA, Lebeau JP, Lettino M, Lip GYH, Pinto FJ, Neil Thomas G, Valgimigli M, van Gelder IC, Watkins CL (2021) 2020 ESC Guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association of Cardio-Thoracic Surgery (EACTS). Eur Heart J 42(5):373–498. https://doi.org/10.1093/eurheartj/ehaa612 Hart RG, Pearce LA, Aguilar MI (2007) Meta-analysis: antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial fibrillation. Ann Intern Med 146(12):857–867. https://doi.org/10.7326/0003-4819-146-12-200706190-00007 Caterina R, Husted S, Wallentin L, Andreotti F, Arnesen H, Bachmann F, Baigent C, Huber K, Jespersen J, Kristensen S, Lip GYH, Morais J, Rasmussen L, Siegbahn A, Verheugt FWA, Weitz JI (2013) 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 110(12):1087–1107. https://doi.org/10.1160/TH13-06-0443 Hylek EM (1996) An analysis of the lowest effective intensity of prophylactic anticoagulation for patients with nonrheumatic atrial fibrillation. N Engl J Med 335(8):540–546. https://doi.org/10.1056/NEJM199608223350802 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 KAA, Califf RM, the ROCKET AF Steering Committee (2011) Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med 365(10):883–891. https://doi.org/10.1056/NEJMoa1009638 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 (2009) Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 361(12):1139–1151. https://doi.org/10.1056/NEJMoa0905561 Granger CB, Alexander JH, McMurray JJV et al (2011) Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med 365(11):981–992. https://doi.org/10.1056/NEJMoa1107039 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 (2013) Edoxaban versus warfarin in patients with atrial fibrillation. N Engl J Med 369(22):2093–2104. https://doi.org/10.1056/NEJMoa1310907 Freedman B, Potpara TS, Lip GYH (2016) Stroke prevention in atrial fibrillation. Lancet 388(10046):806–817. https://doi.org/10.1016/S0140-6736(16)31257-0 Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gøtzsche PC, Ioannidis JPA, Clarke M, Devereaux PJ, Kleijnen J, Moher D (2009) The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. PLoS Med 6(7):e1000100. https://doi.org/10.1371/journal.pmed.1000100 Wells G, Shea B, O’Connell D, et al. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. Accessed February 22, 2021. http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp Cleophas TJ, Zwinderman AH (2017) Modern meta-analysis: review and update of methodologies. Springer International Publishing. https://doi.org/10.1007/978-3-319-55895-0 Begg CB, Mazumdar M (1994) Operating Characteristics of a Rank Correlation Test for Publication Bias. Biometrics. 50(4):1088–1101. https://doi.org/10.2307/2533446 Egger M, Smith GD, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ. 315(7109):629–634. https://doi.org/10.1136/bmj.315.7109.629 Waranugraha Y, Rizal A, Setiawan D, Aziz IJ (2021) The benefit of atrioventricular junction ablation for permanent atrial fibrillation and heart failure patients receiving cardiac resynchronization therapy: an updated systematic review and meta-analysis. Indian Pacing Electrophysiol J 21(2):101–111. https://doi.org/10.1016/j.ipej.2020.12.005 Fletcher J (2007) What is heterogeneity and is it important? BMJ. 334(7584):94–96. https://doi.org/10.1136/bmj.39057.406644.68 Waranugraha Y, Rizal A, Setiawan D, Aziz IJ (2021) Additional complex fractionated atrial electrogram ablation does not improve the outcomes of non-paroxysmal atrial fibrillation: A systematic review and meta-analysis of randomized controlled trials. Indian Heart J 73(1):63–73. https://doi.org/10.1016/j.ihj.2020.11.004 Borenstein M, Hedges LV, Higgins JPT, Rothstein HR, eds. Introduction to Meta-Analysis. Reprinted. Wiley; 2010. Adeboyeje G, Sylwestrzak G, Barron JJ et al (2017) Major bleeding risk during anticoagulation with warfarin, dabigatran, apixaban, or rivaroxaban in patients with nonvalvular atrial fibrillation. J Manag Care Spec Pharm 23(9):968–978. https://doi.org/10.18553/jmcp.2017.23.9.968 Amin A, Keshishian A, Trocio J, Dina O, le H, Rosenblatt L, Liu X, Mardekian J, Zhang Q, Baser O, Vo L (2017) Risk of stroke/systemic embolism, major bleeding and associated costs in non-valvular atrial fibrillation patients who initiated apixaban, dabigatran or rivaroxaban compared with warfarin in the United States Medicare population. Curr Med Res Opin 33(9):1595–1604. https://doi.org/10.1080/03007995.2017.1345729 Bang OY, On YK, Lee M-Y et al (2020) The risk of stroke/systemic embolism and major bleeding in Asian patients with non-valvular atrial fibrillation treated with non-vitamin K oral anticoagulants compared to warfarin: Results from a real-world data analysis. Ai T, ed. PLoS One 15(11):e0242922. https://doi.org/10.1371/journal.pone.0242922 Cha M-J, Choi E-K, Han K-D, Lee SR, Lim WH, Oh S, Lip GYH (2017) Effectiveness and safety of non-vitamin K antagonist oral anticoagulants in Asian patients with atrial fibrillation. Stroke. 48(11):3040–3048. https://doi.org/10.1161/STROKEAHA.117.018773 Chan Y, See L, Tu H et al (2018) Efficacy and safety of apixaban, dabigatran, rivaroxaban, and warfarin in Asians with nonvalvular atrial fibrillation. J Am Heart Assoc 7(8):e008150. https://doi.org/10.1161/JAHA.117.008150 Chan Y-H, Lee H-F, See L-C, Tu HT, Chao TF, Yeh YH, Wu LS, Kuo CT, Chang SH, Lip GYH (2019) Effectiveness and safety of four direct oral anticoagulants in Asian patients with nonvalvular atrial fibrillation. Chest. 156(3):529–543. https://doi.org/10.1016/j.chest.2019.04.108 Cho MS, Yun JE, Park JJ, Kim YJ, Lee J, Kim H, Park DW, Nam GB (2019) Outcomes after use of standard- and low-dose non–vitamin k oral anticoagulants in Asian patients with atrial fibrillation. Stroke. 50(1):110–118. https://doi.org/10.1161/STROKEAHA.118.023093 Coleman CI, Peacock WF, Bunz TJ, Alberts MJ (2017) Effectiveness and safety of apixaban, dabigatran, and rivaroxaban versus warfarin in patients with nonvalvular atrial fibrillation and previous stroke or transient ischemic attack. Stroke. 48(8):2142–2149. https://doi.org/10.1161/STROKEAHA.117.017474 Costa OS, Beyer-Westendorf J, Ashton V, Milentijevic D, Moore KT, Bunz TJ, Coleman CI (2020) Effectiveness and safety of rivaroxaban versus warfarin in obese nonvalvular atrial fibrillation patients: analysis of electronic health record data. Curr Med Res Opin 36(7):1081–1088. https://doi.org/10.1080/03007995.2020.1762554 Deitelzweig S, Luo X, Gupta K, Trocio J, Mardekian J, Curtice T, Lingohr-Smith M, Menges B, Lin J (2017) Comparison of effectiveness and safety of treatment with apixaban vs. other oral anticoagulants among elderly nonvalvular atrial fibrillation patients. Curr Med Res Opin 33(10):1745–1754. https://doi.org/10.1080/03007995.2017.1334638 Graham DJ, Reichman ME, Wernecke M, Zhang R, Southworth MR, Levenson M, Sheu TC, Mott K, Goulding MR, Houstoun M, MaCurdy TE, Worrall C, Kelman JA (2015) Cardiovascular, bleeding, and mortality risks in elderly medicare patients treated with dabigatran or warfarin for nonvalvular atrial fibrillation. Circulation. 131(2):157–164. https://doi.org/10.1161/CIRCULATIONAHA.114.012061 Graham DJ, Baro E, Zhang R et al (2019) Comparative stroke, bleeding, and mortality risks in older medicare patients treated with oral anticoagulants for nonvalvular atrial fibrillation. Am J Med 132(5):596–604.e11. https://doi.org/10.1016/j.amjmed.2018.12.023 Halvorsen S, Ghanima W, Fride Tvete I, Hoxmark C, Falck P, Solli O, Jonasson C (2017) A nationwide registry study to compare bleeding rates in patients with atrial fibrillation being prescribed oral anticoagulants. Eur Heart J - Cardiovasc Pharmacother 3(1):28–36. https://doi.org/10.1093/ehjcvp/pvw031 Hernandez I, Baik SH, Piñera A, Zhang Y (2015) Risk of Bleeding With Dabigatran in Atrial Fibrillation. JAMA Intern Med 175(1):18–24. https://doi.org/10.1001/jamainternmed.2014.5398 Hsu C-C, Hsu P-F, Sung S-H, Tu ST, Yu BH, Huang CJ, Cheng HM (2018) Is there a preferred stroke prevention strategy for diabetic patients with non-valvular atrial fibrillation? Comparing warfarin, dabigatran and rivaroxaban. Thromb Haemost 118(01):072–081. https://doi.org/10.1160/TH17-02-0095 Huybrechts KF, Gopalakrishnan C, Bartels DB, Zint K, Gurusamy VK, Landon J, Schneeweiss S (2020) Safety and effectiveness of dabigatran and other direct oral anticoagulants compared with warfarin in patients with atrial fibrillation. Clin Pharmacol Ther 107(6):1405–1419. https://doi.org/10.1002/cpt.1753 Kjerpeseth LJ, Selmer R, Ariansen I, Karlstad Ø, Ellekjær H, Skovlund E (2019) Comparative effectiveness of warfarin, dabigatran, rivaroxaban and apixaban in non-valvular atrial fibrillation: A nationwide pharmacoepidemiological study. Garcia de Frutos P, ed. PLoS One 14(8):e0221500. https://doi.org/10.1371/journal.pone.0221500 Kohsaka S, Katada J, Saito K, Jenkins A, Li B, Mardekian J, Terayama Y (2020) Safety and effectiveness of non-vitamin K oral anticoagulants versus warfarin in real-world patients with non-valvular atrial fibrillation: a retrospective analysis of contemporary Japanese administrative claims data. Open Heart 7(1):e001232. https://doi.org/10.1136/openhrt-2019-001232 Larsen TB, Skjøth F, Nielsen PB, Kjældgaard JN, Lip GYH. Comparative effectiveness and safety of non-vitamin K antagonist oral anticoagulants and warfarin in patients with atrial fibrillation: propensity weighted nationwide cohort study. BMJ. Published online June 16, 2016:i3189. doi:https://doi.org/10.1136/bmj.i3189 Lauffenburger JC, Farley JF, Gehi AK, Rhoney DH, Brookhart MA, Fang G (2015) Effectiveness and safety of dabigatran and warfarin in real-world US patients with non-valvular atrial fibrillation: a retrospective cohort study. J Am Heart Assoc 4(4):e001798. https://doi.org/10.1161/JAHA.115.001798 Lee S-R, Choi E-K, Han K-D, Jung J-H, Oh S, Lip GYH (2018) Edoxaban in Asian patients with atrial fibrillation. J Am Coll Cardiol 72(8):838–853. https://doi.org/10.1016/j.jacc.2018.05.066 Lee S-R, Choi E-K, Han K-D, Jung JH, Cha MJ, Oh S, Lip GYH (2019) Non–vitamin K antagonist oral anticoagulants in Asian patients with supranormal renal function. Stroke. 50(6):1480–1489. https://doi.org/10.1161/STROKEAHA.118.024264 Lee S-R, Choi E-K, Kwon S, Han KD, Jung JH, Cha MJ, Oh S, Lip GYH (2019) Effectiveness and safety of contemporary oral anticoagulants among Asians with nonvalvular atrial fibrillation. Stroke. 50(8):2245–2249. https://doi.org/10.1161/STROKEAHA.119.025536 Li X, Deitelzweig S, Keshishian A, Hamilton M, Horblyuk R, Gupta K, Luo X, Mardekian J, Friend K, Nadkarni A, Pan X, Lip GYH (2017) Effectiveness and safety of apixaban versus warfarin in non-valvular atrial fibrillation patients in “real-world” clinical practice: A propensity-matched analysis of 76,940 patients. Thromb Haemost 117(06):1072–1082. https://doi.org/10.1160/TH17-01-0068 Lip GYH, Pan X, Kamble S, Kawabata H, Mardekian J, Masseria C, Bruno A, Phatak H (2016) Major bleeding risk among non-valvular atrial fibrillation patients initiated on apixaban, dabigatran, rivaroxaban or warfarin: a “real-world” observational study in the United States. Int J Clin Pract 70(9):752–763. https://doi.org/10.1111/ijcp.12863 Lip GYH, Keshishian A, Kamble S, Pan X, Mardekian J, Horblyuk R, Hamilton M (2016) Real-world comparison of major bleeding risk among non-valvular atrial fibrillation patients initiated on apixaban, dabigatran, rivaroxaban, or warfarin: A propensity score matched analysis. Thromb Haemost 116(11):975–986. https://doi.org/10.1160/TH16-05-0403 Maura G, Blotière P-O, Bouillon K, Billionnet C, Ricordeau P, Alla F, Zureik M (2015) Comparison of the short-term risk of bleeding and arterial thromboembolic events in nonvalvular atrial fibrillation patients newly treated with dabigatran or rivaroxaban versus vitamin K antagonists: a French Nationwide Propensity-Matched Cohort Study. Circulation. 132(13):1252–1260. https://doi.org/10.1161/CIRCULATIONAHA.115.015710 Mitsuntisuk P, Nathisuwan S, Junpanichjaroen A, et al. Real-world comparative effectiveness and safety of non-vitamin K antagonist oral anticoagulants vs. warfarin in a developing country. Clin Pharmacol Ther. Published online November 22, 2020:cpt.2090. doi:10.1002/cpt.2090 Nielsen PB, Skjøth F, Søgaard M, Kjældgaard JN, Lip GYH, Larsen TB (2017) 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. 356:j510. https://doi.org/10.1136/bmj.j510 Rutherford O-CW, Jonasson C, Ghanima W, Söderdahl F, Halvorsen S (2020) Comparison of dabigatran, rivaroxaban, and apixaban for effectiveness and safety in atrial fibrillation: a nationwide cohort study. Eur Heart J - Cardiovasc Pharmacother 6(2):75–85. https://doi.org/10.1093/ehjcvp/pvz086 Staerk L, Fosbøl EL, Lip GYH, Lamberts M, Bonde AN, Torp-Pedersen C, Ozenne B, Gerds TA, Gislason GH, Olesen JB (2017) Ischaemic and haemorrhagic stroke associated with non-vitamin K antagonist oral anticoagulants and warfarin use in patients with atrial fibrillation: a nationwide cohort study. Eur Heart J 38:907–915. https://doi.org/10.1093/eurheartj/ehw496 Villines TC, Schnee J, Fraeman K, Siu K, Reynolds MW, Collins J, Schwartzman E (2015) A comparison of the safety and effectiveness of dabigatran and warfarin in non-valvular atrial fibrillation patients in a large healthcare system. Thromb Haemost 114(12):1290–1298. https://doi.org/10.1160/TH15-06-0453 Yao X, Abraham NS, Sangaralingham LR, Bellolio MF, McBane RD, Shah ND, Noseworthy PA (2016) Effectiveness and safety of dabigatran, rivaroxaban, and apixaban versus warfarin in nonvalvular atrial fibrillation. J Am Heart Assoc 5(6):e003725. https://doi.org/10.1161/JAHA.116.003725 Yu HT, Yang P-S, Kim T-H, Jang E, Kim D, Uhm JS, Kim JY, Pak HN, Lee MH, Lip GYH, Joung B (2018) Impact of renal function on outcomes with edoxaban in real-world patients with atrial fibrillation: a nationwide cohort study. Stroke. 49(10):2421–2429. https://doi.org/10.1161/STROKEAHA.118.021387 Wang YP, Kehar R, Iansavitchene A, Lazo-Langner A (2020) Bleeding risk in nonvalvular atrial fibrillation patients receiving direct oral anticoagulants and warfarin: a systematic review and meta-analysis of observational studies. TH Open 04(03):e145–e152. https://doi.org/10.1055/s-0040-1714918 Capodanno D, Capranzano P, Giacchi G, Calvi V, Tamburino C (2013) Novel oral anticoagulants versus warfarin in non-valvular atrial fibrillation: A meta-analysis of 50,578 patients. Int J Cardiol 167(4):1237–1241. https://doi.org/10.1016/j.ijcard.2012.03.148 Hicks T, Stewart F, Eisinga A (2016) NOACs versus warfarin for stroke prevention in patients with AF: a systematic review and meta-analysis. Open Heart 3(1):e000279. https://doi.org/10.1136/openhrt-2015-000279 Xue Z, Zhou Y, Wu C, Lin J, Liu X, Zhu W (2020) Non-vitamin K antagonist oral anticoagulants in Asian patients with atrial fibrillation: evidences from the real-world data. Heart Fail Rev 25(6):957–964. https://doi.org/10.1007/s10741-019-09878-y Ruff CT, Giugliano RP, Braunwald E, Hoffman EB, Deenadayalu N, Ezekowitz MD, Camm AJ, Weitz JI, Lewis BS, Parkhomenko A, Yamashita T, Antman EM (2014) Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials. Lancet 383(9921):955–962. https://doi.org/10.1016/S0140-6736(13)62343-0 Chan Y-H, Lee H-F, Chao T-F, Wu CT, Chang SH, Yeh YH, See LC, Kuo CT, Chu PH, Wang CL, Lip GYH (2019) Real-world comparisons of direct oral anticoagulants for stroke prevention in asian patients with non-valvular atrial fibrillation: a systematic review and meta-analysis. Cardiovasc Drugs Ther 33(6):701–710. https://doi.org/10.1007/s10557-019-06910-z Proietti M, Romanazzi I, Romiti GF, Farcomeni A, Lip GYH (2018) Real-world use of apixaban for stroke prevention in atrial fibrillation: a systematic review and meta-analysis. Stroke. 49(1):98–106. https://doi.org/10.1161/STROKEAHA.117.018395 Wadhera RK, Russell CE, Piazza G (2014) Warfarin versus novel oral anticoagulants: how to choose? Circulation. 130(22):e191–e193. https://doi.org/10.1161/CIRCULATIONAHA.114.010426 Mekaj A, Mekaj Y, Duci S, Miftari E (2015) New oral anticoagulants: their advantages and disadvantages compared with vitamin K antagonists in the prevention and treatment of patients with thromboembolic events. Ther Clin Risk Manag 11:967–977. https://doi.org/10.2147/TCRM.S84210