Skip to main content
Top
Published in: BMC Cardiovascular Disorders 1/2019

Open Access 01-12-2019 | Dabigatran | Research article

Indirect comparison of novel Oral anticoagulants among Asians with non-Valvular atrial fibrillation in the real world setting: a network meta-analysis

Authors: Jianchao Zhang, Junnan Tang, Xiaolin Cui, Bo Wang, Mengsen Bu, Yan Bai, Kai Wang, Jiacheng Guo, Deliang Shen, Jinying Zhang

Published in: BMC Cardiovascular Disorders | Issue 1/2019

Login to get access

Abstract

Background

The development of novel oral anticoagulants (NOACs) has changed the landscape of non-valvular atrial fibrillation (NVAF) management. In this study, the effectiveness and the safety of several NOACs were evaluated in a real-world setting among Asian patients with NVAF.

Methods

The literature search was conducted crossing different databases including Embase, MEDLINE, and the Cochrane Library from inception through March 1, 2019, for studies which included real-world perspectives comparing the individual NOACs with each other or with warfarin among Asians with NVAF. The primary outcomes were defined as stroke or systemic embolism (SSE) and major bleeding; ischemic stroke, all-cause death as well as intracranial bleeding were classified as the secondary outcomes.

Results

From sixteen real-world studies, a total of 312,827 Asian patients were included in this analysis. In comparison with warfarin, the utilization of apixaban, dabigatran, and rivaroxaban significantly lowered the risk of major bleeding (apixaban: HR 0.47, 95%CI 0.35–0.63; dabigatran: HR 0.59, 95%CI 0.47–0.73; rivaroxaban: HR 0.66, 95%CI 0.52–0.83) and lessened the all-cause death rate (apixaban: HR 0.29, 95%CI 0.16–0.52; dabigatran: HR 0.40, 95%CI 0.27–0.60; rivaroxaban: HR 0.42, 95%CI 0.28–0.65). Apixaban (HR 0.59; 95%CI 0.40–0.85) reduced the possibility of ischemic stroke when compared against dabigatran. Rivaroxaban showed a higher chance of causing an ischemic stroke (HR 1.61; 95%CI 1.08–2.41) and major bleeding (HR 1.39; 95%CI 1.02–1.90) than Apixaban.

Conclusions

Apixaban, dabigatran and rivaroxaban were more effective than warfarin on reducing the risks of stroke and haemorrhage; meanwhile, apixaban was likely to lower the risk of major bleeding comparing to rivaroxaban.

Trial registration

PROSPERO registry number: CRD42018086914.
Appendix
Available only for authorised users
Literature
1.
go back to reference Kirchhof P, Benussi S, Kotecha D, et al. 2016 ESC guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur J Cardiothorac Surg. 2016;50(5):e1–e88.CrossRef Kirchhof P, Benussi S, Kotecha D, et al. 2016 ESC guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur J Cardiothorac Surg. 2016;50(5):e1–e88.CrossRef
2.
go back to reference Bai Y, Wang YL, Shantsila A, GYH L. The global burden of atrial fibrillation and stroke: a systematic review of the clinical epidemiology of atrial fibrillation in Asia. Chest. 2017;152(4):810–20.CrossRef Bai Y, Wang YL, Shantsila A, GYH L. The global burden of atrial fibrillation and stroke: a systematic review of the clinical epidemiology of atrial fibrillation in Asia. Chest. 2017;152(4):810–20.CrossRef
3.
go back to reference Hart RG, Pearce LA, Aguilar MI. Meta-analysis: antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial fibrillation. Ann Intern Med. 2007;146(12):857–67.CrossRef Hart RG, Pearce LA, Aguilar MI. Meta-analysis: antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial fibrillation. Ann Intern Med. 2007;146(12):857–67.CrossRef
4.
go back to reference Deitelzweig S, Farmer C, Luo X, et al. Comparison of major bleeding risk in patients with non-valvular atrial fibrillation receiving direct oral anticoagulants in the real-world setting: a network meta-analysis. Curr Med Res Opin. 2018;34(3):487–98.CrossRef Deitelzweig S, Farmer C, Luo X, et al. Comparison of major bleeding risk in patients with non-valvular atrial fibrillation receiving direct oral anticoagulants in the real-world setting: a network meta-analysis. Curr Med Res Opin. 2018;34(3):487–98.CrossRef
5.
go back to reference Mazurek M, Huisman MV, Rothman KJ, et al. Regional differences in antithrombotic treatment for atrial fibrillation: insights from the GLORIA-AF phase II registry. Thromb Haemost. 2017;117(12):2376–88.CrossRef Mazurek M, Huisman MV, Rothman KJ, et al. Regional differences in antithrombotic treatment for atrial fibrillation: insights from the GLORIA-AF phase II registry. Thromb Haemost. 2017;117(12):2376–88.CrossRef
6.
go back to reference Liu T, Hui J, Hou YY, et al. Meta-analysis of efficacy and safety of low-intensity warfarin therapy for east Asian patients with Nonvalvular atrial fibrillation. Am J Cardiol. 2017;120(9):1562–7.CrossRef Liu T, Hui J, Hou YY, et al. Meta-analysis of efficacy and safety of low-intensity warfarin therapy for east Asian patients with Nonvalvular atrial fibrillation. Am J Cardiol. 2017;120(9):1562–7.CrossRef
7.
go back to reference 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):955–62.CrossRef 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):955–62.CrossRef
8.
go back to reference Woo HG, Chung I, Gwak DS, et al. Intracerebral hemorrhage associated with warfarin versus non-vitamin K antagonist oral anticoagulants in Asian patients. J Clin Neurosci. 2019;61:160–5.CrossRef Woo HG, Chung I, Gwak DS, et al. Intracerebral hemorrhage associated with warfarin versus non-vitamin K antagonist oral anticoagulants in Asian patients. J Clin Neurosci. 2019;61:160–5.CrossRef
9.
go back to reference Wang KL, Lip GY, Lin SJ, Chiang CE. Non-vitamin K antagonist Oral anticoagulants for stroke prevention in Asian patients with Nonvalvular atrial fibrillation: meta-analysis. Stroke. 2015;46(9):2555–61.CrossRef Wang KL, Lip GY, Lin SJ, Chiang CE. Non-vitamin K antagonist Oral anticoagulants for stroke prevention in Asian patients with Nonvalvular atrial fibrillation: meta-analysis. Stroke. 2015;46(9):2555–61.CrossRef
10.
go back to reference 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(4):309–15.CrossRef 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(4):309–15.CrossRef
11.
go back to reference Lee SR, Choi EK, Han KD, Cha MJ, Oh S, GYH L. 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(12):e0189495.CrossRef Lee SR, Choi EK, Han KD, Cha MJ, Oh S, GYH L. 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(12):e0189495.CrossRef
12.
go back to reference Baek S, Park SH, Won E, Park YR, Kim HJ. Propensity score matching: a conceptual review for radiology researchers. Korean J Radiol. 2015;16(2):286–96.CrossRef Baek S, Park SH, Won E, Park YR, Kim HJ. Propensity score matching: a conceptual review for radiology researchers. Korean J Radiol. 2015;16(2):286–96.CrossRef
15.
go back to reference Chaimani A, Higgins JP, Mavridis D, Spyridonos P, Salanti G. Graphical tools for network meta-analysis in STATA. PLoS One. 2013;8(10):e76654.CrossRef Chaimani A, Higgins JP, Mavridis D, Spyridonos P, Salanti G. Graphical tools for network meta-analysis in STATA. PLoS One. 2013;8(10):e76654.CrossRef
16.
go back to reference Salanti G, Ades AE, Ioannidis JP. Graphical methods and numerical summaries for presenting results from multiple-treatment meta-analysis: an overview and tutorial. J Clin Epidemiol. 2011;64(2):163–71.CrossRef Salanti G, Ades AE, Ioannidis JP. Graphical methods and numerical summaries for presenting results from multiple-treatment meta-analysis: an overview and tutorial. J Clin Epidemiol. 2011;64(2):163–71.CrossRef
17.
go back to reference Ho JC, Chang AM, Yan BP, Yu CM, Lam YY, Lee VW. Dabigatran compared with warfarin for stroke prevention with atrial fibrillation: experience in Hong Kong. Clin Cardiol. 2012;35(12):E40–5.CrossRef Ho JC, Chang AM, Yan BP, Yu CM, Lam YY, Lee VW. Dabigatran compared with warfarin for stroke prevention with atrial fibrillation: experience in Hong Kong. Clin Cardiol. 2012;35(12):E40–5.CrossRef
18.
go back to reference Yap LB, Eng DT, Sivalingam L, et al. A comparison of dabigatran with warfarin for stroke prevention in atrial fibrillation in an Asian population. Clin Appl Thromb Hemost. 2016;22(8):792–7.CrossRef Yap LB, Eng DT, Sivalingam L, et al. A comparison of dabigatran with warfarin for stroke prevention in atrial fibrillation in an Asian population. Clin Appl Thromb Hemost. 2016;22(8):792–7.CrossRef
19.
go back to reference Chan YH, Yen KC, See LC, et al. Cardiovascular, bleeding, and mortality risks of dabigatran in Asians with Nonvalvular atrial fibrillation. Stroke. 2016;47(2):441–9.CrossRef Chan YH, Yen KC, See LC, et al. Cardiovascular, bleeding, and mortality risks of dabigatran in Asians with Nonvalvular atrial fibrillation. Stroke. 2016;47(2):441–9.CrossRef
20.
go back to reference Chan YH, Kuo CT, Yeh YH, et al. Thromboembolic, bleeding, and mortality risks of rivaroxaban and dabigatran in Asians with Nonvalvular atrial fibrillation. J Am Coll Cardiol. 2016;68(13):1389–401.CrossRef Chan YH, Kuo CT, Yeh YH, et al. Thromboembolic, bleeding, and mortality risks of rivaroxaban and dabigatran in Asians with Nonvalvular atrial fibrillation. J Am Coll Cardiol. 2016;68(13):1389–401.CrossRef
21.
go back to reference Cha MJ, Choi EK, Han KD, et al. Effectiveness and safety of non-vitamin K antagonist Oral anticoagulants in Asian patients with atrial fibrillation. Stroke. 2017;48(11):3040–8.CrossRef Cha MJ, Choi EK, Han KD, et al. Effectiveness and safety of non-vitamin K antagonist Oral anticoagulants in Asian patients with atrial fibrillation. Stroke. 2017;48(11):3040–8.CrossRef
22.
go back to reference Naganuma M, Shiga T, Nagao T, Suzuki A, Murasaki K, Hagiwara N. Effectiveness and safety of dabigatran versus warfarin in "real-world" Japanese patients with atrial fibrillation: a single-center observational study. J Arrhythm. 2017;33(2):107–10.CrossRef Naganuma M, Shiga T, Nagao T, Suzuki A, Murasaki K, Hagiwara N. Effectiveness and safety of dabigatran versus warfarin in "real-world" Japanese patients with atrial fibrillation: a single-center observational study. J Arrhythm. 2017;33(2):107–10.CrossRef
23.
go back to reference Lai CL, Chen HM, Liao MT, Lin TT, Chan KA. Comparative Effectiveness and Safety of Dabigatran and Rivaroxaban in Atrial Fibrillation Patients. J Am Heart Assoc. 2017. 6(4). Lai CL, Chen HM, Liao MT, Lin TT, Chan KA. Comparative Effectiveness and Safety of Dabigatran and Rivaroxaban in Atrial Fibrillation Patients. J Am Heart Assoc. 2017. 6(4).
24.
go back to reference Kohsaka S, Murata T, Izumi N, Katada J, Wang F, Terayama Y. Bleeding risk of apixaban, dabigatran, and low-dose rivaroxaban compared with warfarin in Japanese patients with non-valvular atrial fibrillation: a propensity matched analysis of administrative claims data. Curr Med Res Opin. 2017;33(11):1955–63.CrossRef Kohsaka S, Murata T, Izumi N, Katada J, Wang F, Terayama Y. Bleeding risk of apixaban, dabigatran, and low-dose rivaroxaban compared with warfarin in Japanese patients with non-valvular atrial fibrillation: a propensity matched analysis of administrative claims data. Curr Med Res Opin. 2017;33(11):1955–63.CrossRef
25.
go back to reference Hsu CC, Hsu PF, Sung SH, et al. Is there a preferred stroke prevention strategy for diabetic patients with non-Valvular atrial fibrillation? Comparing warfarin. Dabigatran and Rivaroxaban Thromb Haemost. 2018;118(1):72–81.CrossRef Hsu CC, Hsu PF, Sung SH, et al. Is there a preferred stroke prevention strategy for diabetic patients with non-Valvular atrial fibrillation? Comparing warfarin. Dabigatran and Rivaroxaban Thromb Haemost. 2018;118(1):72–81.CrossRef
26.
go back to reference Deitelzweig S, Luo X, Gupta K, et al. Comparison of effectiveness and safety of treatment with apixaban vs. other oral anticoagulants among elderly nonvalvular atrial fibrillation patients. Curr Med Res Opin. 2017;33(10):1745–54.CrossRef Deitelzweig S, Luo X, Gupta K, et al. Comparison of effectiveness and safety of treatment with apixaban vs. other oral anticoagulants among elderly nonvalvular atrial fibrillation patients. Curr Med Res Opin. 2017;33(10):1745–54.CrossRef
27.
go back to reference Lee HF, Chan YH, Chang SH, et al. Effectiveness and safety of non-vitamin K antagonist Oral anticoagulant and warfarin in cirrhotic patients with Nonvalvular atrial fibrillation. J Am Heart Assoc. 2019;8(5):e011112.CrossRef Lee HF, Chan YH, Chang SH, et al. Effectiveness and safety of non-vitamin K antagonist Oral anticoagulant and warfarin in cirrhotic patients with Nonvalvular atrial fibrillation. J Am Heart Assoc. 2019;8(5):e011112.CrossRef
28.
go back to reference Huang HY, Lin SY, Cheng SH, Wang CC. Effectiveness and safety of different rivaroxaban dosage regimens in patients with non-Valvular atrial fibrillation: a Nationwide. Population-Based Cohort Study Sci Rep. 2018;8(1):3451.PubMed Huang HY, Lin SY, Cheng SH, Wang CC. Effectiveness and safety of different rivaroxaban dosage regimens in patients with non-Valvular atrial fibrillation: a Nationwide. Population-Based Cohort Study Sci Rep. 2018;8(1):3451.PubMed
29.
go back to reference Chan YH, See LC, Tu HT, et al. Efficacy and Safety of Apixaban, Dabigatran, Rivaroxaban, and Warfarin in Asians With Nonvalvular Atrial Fibrillation. J Am Heart Assoc. 2018. 7(8). Chan YH, See LC, Tu HT, et al. Efficacy and Safety of Apixaban, Dabigatran, Rivaroxaban, and Warfarin in Asians With Nonvalvular Atrial Fibrillation. J Am Heart Assoc. 2018. 7(8).
30.
go back to reference Jeong HK, Lee KH, Park HW, et al. Real world comparison of rivaroxaban and warfarin in Korean patients with atrial fibrillation: propensity matching cohort analysis. Chonnam Med J. 2019;55(1):54–61.CrossRef Jeong HK, Lee KH, Park HW, et al. Real world comparison of rivaroxaban and warfarin in Korean patients with atrial fibrillation: propensity matching cohort analysis. Chonnam Med J. 2019;55(1):54–61.CrossRef
31.
go back to reference Koretsune Y, Yamashita T, Yasaka M, et al. Comparative effectiveness and safety of warfarin and dabigatran in patients with non-valvular atrial fibrillation in Japan: a claims database analysis. J Cardiol. 2019;73(3):204–9.CrossRef Koretsune Y, Yamashita T, Yasaka M, et al. Comparative effectiveness and safety of warfarin and dabigatran in patients with non-valvular atrial fibrillation in Japan: a claims database analysis. J Cardiol. 2019;73(3):204–9.CrossRef
32.
go back to reference Cho MS, Yun JE, Park JJ, et al. Outcomes After Use of Standard- and Low-Dose Non-Vitamin K Oral Anticoagulants in Asian Patients with Atrial Fibrillation. Stroke. 2018: STROKEAHA118023093. Cho MS, Yun JE, Park JJ, et al. Outcomes After Use of Standard- and Low-Dose Non-Vitamin K Oral Anticoagulants in Asian Patients with Atrial Fibrillation. Stroke. 2018: STROKEAHA118023093.
33.
go back to reference Akao M, Chun YH, Esato M, et al. Inappropriate use of oral anticoagulants for patients with atrial fibrillation. Circ J. 2014;78(9):2166–72.CrossRef Akao M, Chun YH, Esato M, et al. Inappropriate use of oral anticoagulants for patients with atrial fibrillation. Circ J. 2014;78(9):2166–72.CrossRef
34.
go back to reference Teo KC, Mahboobani NR, Lee R, et al. Warfarin associated intracerebral hemorrhage in Hong Kong Chinese. Neurol Res. 2014;36(2):143–9.CrossRef Teo KC, Mahboobani NR, Lee R, et al. Warfarin associated intracerebral hemorrhage in Hong Kong Chinese. Neurol Res. 2014;36(2):143–9.CrossRef
35.
go back to reference Rasmussen LH, Larsen TB, Graungaard T, Skjøth F, Lip GY. Primary and secondary prevention with new oral anticoagulant drugs for stroke prevention in atrial fibrillation: indirect comparison analysis. BMJ. 2012;345:e7097.CrossRef Rasmussen LH, Larsen TB, Graungaard T, Skjøth F, Lip GY. Primary and secondary prevention with new oral anticoagulant drugs for stroke prevention in atrial fibrillation: indirect comparison analysis. BMJ. 2012;345:e7097.CrossRef
36.
go back to reference Lip GY, Mitchell SA, Liu X, et al. Relative efficacy and safety of non-vitamin K oral anticoagulants for non-valvular atrial fibrillation: network meta-analysis comparing apixaban, dabigatran, rivaroxaban and edoxaban in three patient subgroups. Int J Cardiol. 2016;204:88–94.CrossRef Lip GY, Mitchell SA, Liu X, et al. Relative efficacy and safety of non-vitamin K oral anticoagulants for non-valvular atrial fibrillation: network meta-analysis comparing apixaban, dabigatran, rivaroxaban and edoxaban in three patient subgroups. Int J Cardiol. 2016;204:88–94.CrossRef
37.
go back to reference Proietti M, Romanazzi I, Romiti GF, Farcomeni A, GYH L. Real-world use of Apixaban for stroke prevention in atrial fibrillation: a systematic review and meta-analysis. Stroke. 2018;49(1):98–106.CrossRef Proietti M, Romanazzi I, Romiti GF, Farcomeni A, GYH L. Real-world use of Apixaban for stroke prevention in atrial fibrillation: a systematic review and meta-analysis. Stroke. 2018;49(1):98–106.CrossRef
38.
go back to reference Tawfik A, Bielecki JM, Krahn M, et al. Systematic review and network meta-analysis of stroke prevention treatments in patients with atrial fibrillation. Clin Pharmacol. 2016;8:93–107.PubMedPubMedCentral Tawfik A, Bielecki JM, Krahn M, et al. Systematic review and network meta-analysis of stroke prevention treatments in patients with atrial fibrillation. Clin Pharmacol. 2016;8:93–107.PubMedPubMedCentral
39.
go back to reference Roche N, Reddel H, Martin R, et al. Quality standards for real-world research. Focus on observational database studies of comparative effectiveness. Ann Am Thorac Soc. 2014. 11 Suppl 2: S99–104.CrossRef Roche N, Reddel H, Martin R, et al. Quality standards for real-world research. Focus on observational database studies of comparative effectiveness. Ann Am Thorac Soc. 2014. 11 Suppl 2: S99–104.CrossRef
40.
go back to reference de Lusignan S, Crawford L, Munro N. Creating and using real-world evidence to answer questions about clinical effectiveness. J Innov Health Inform. 2015;22(3):368–73.CrossRef de Lusignan S, Crawford L, Munro N. Creating and using real-world evidence to answer questions about clinical effectiveness. J Innov Health Inform. 2015;22(3):368–73.CrossRef
41.
go back to reference Kardos P, Worsley S, Singh D, Román-Rodríguez M, Newby DE, Müllerová H. Randomized controlled trials and real-world observational studies in evaluating cardiovascular safety of inhaled bronchodilator therapy in COPD. Int J Chron Obstruct Pulmon Dis. 2016;11:2885–95.CrossRef Kardos P, Worsley S, Singh D, Román-Rodríguez M, Newby DE, Müllerová H. Randomized controlled trials and real-world observational studies in evaluating cardiovascular safety of inhaled bronchodilator therapy in COPD. Int J Chron Obstruct Pulmon Dis. 2016;11:2885–95.CrossRef
42.
go back to reference Wang KL, Giugliano RP, Goto S, et al. Standard dose versus low dose non-vitamin K antagonist oral anticoagulants in Asian patients with atrial fibrillation: a meta-analysis of contemporary randomized controlled trials. Heart Rhythm. 2016;13(12):2340–7.CrossRef Wang KL, Giugliano RP, Goto S, et al. Standard dose versus low dose non-vitamin K antagonist oral anticoagulants in Asian patients with atrial fibrillation: a meta-analysis of contemporary randomized controlled trials. Heart Rhythm. 2016;13(12):2340–7.CrossRef
43.
go back to reference Gamra H, Murin J, Chiang CE, Naditch-Brûlé L, Brette S, Steg PG. Use of antithrombotics in atrial fibrillation in Africa, Europe, Asia and South America: insights from the international RealiseAF survey. Arch Cardiovasc Dis. 2014;107(2):77–87.CrossRef Gamra H, Murin J, Chiang CE, Naditch-Brûlé L, Brette S, Steg PG. Use of antithrombotics in atrial fibrillation in Africa, Europe, Asia and South America: insights from the international RealiseAF survey. Arch Cardiovasc Dis. 2014;107(2):77–87.CrossRef
44.
go back to reference Lee KH, Park HW, Lee N, et al. Optimal dose of dabigatran for the prevention of thromboembolism with minimal bleeding risk in Korean patients with atrial fibrillation. Europace. 2017. 19(suppl_4): iv1-iv9.CrossRef Lee KH, Park HW, Lee N, et al. Optimal dose of dabigatran for the prevention of thromboembolism with minimal bleeding risk in Korean patients with atrial fibrillation. Europace. 2017. 19(suppl_4): iv1-iv9.CrossRef
Metadata
Title
Indirect comparison of novel Oral anticoagulants among Asians with non-Valvular atrial fibrillation in the real world setting: a network meta-analysis
Authors
Jianchao Zhang
Junnan Tang
Xiaolin Cui
Bo Wang
Mengsen Bu
Yan Bai
Kai Wang
Jiacheng Guo
Deliang Shen
Jinying Zhang
Publication date
01-12-2019
Publisher
BioMed Central
Published in
BMC Cardiovascular Disorders / Issue 1/2019
Electronic ISSN: 1471-2261
DOI
https://doi.org/10.1186/s12872-019-1165-5

Other articles of this Issue 1/2019

BMC Cardiovascular Disorders 1/2019 Go to the issue