Subscribe to RSS
DOI: 10.1055/s-0043-1772773
Non-vitamin K Antagonist Oral Anticoagulant, Warfarin, and ABC Pathway Adherence on Hierarchical Outcomes: Win Ratio Analysis of the COOL-AF Registry
Funding This study was funded by a grant from the Health System Research Institute (grant number 59–053), and the Heart Association of Thailand under the Royal Patronage of H.M. the King. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Abstract
Background Atrial fibrillation (AF) Better Care (ABC) pathway adherence is associated with improved outcomes. Clinical trials have shown that non-vitamin K antagonist oral anticoagulants (NOACs) are as least as effective as warfarin for stroke prevention in AF patients. The Win Ratio method, analyzing hierarchical composite outcomes considering event timing and severity, has limited data on its use in Asians.
Objectives We aim to apply Win Ratio in a registry to access the comparative effectiveness of NOACs versus warfarin and ABC adherence versus nonadherence in Asian patients with AF.
Methods Our study included nonvalvular AF patients from the nationwide prospective COOL-AF registry in Thailand. The NOAC-treated group was compared with the warfarin-treated group using the Win Ratio, with the following order: all-cause death, intracranial hemorrhage (ICH), ischemic stroke/transient ischemic attack/systemic embolism, non-ICH major bleeding, and myocardial infarction or heart failure. ABC pathway adherence versus nonadherence was also compared. A Win Ratio greater than 1.00 indicating a better outcome.
Results The analysis included 2,568 patients, with 228 in the NOAC group and 2,340 in the warfarin group. The NOAC group had more wins than the warfarin group, with an unmatched Win Ratio of 1.64 (95% confidence interval [CI]: 1.22–2.20; p < 0.001). When compared with nonadherence, ABC pathway adherence was associated with a Win Ratio of 1.57 (95% CI: 1.33–1.85; p < 0.001).
Conclusion This Win Ratio analysis demonstrates the significant benefits of NOACs over warfarin and ABC pathway adherence over nonadherence in reducing the composite outcome in patients with AF.
Keywords
hierarchical composite outcome - atrial fibrillation - anticoagulants - ABC pathway - thrombosisData Availability Statement
The data used in this analysis are available from the corresponding author upon reasonable request.
Authors' Contribution
All authors made substantial contributions to conception and design, data interpretation, and revising the manuscript critically for important intellectual content. S.T. and R.K. made contributions to drafting and acquisition of data. S.T. made contributions to data analysis and figure drawing. All authors approved the final version to be published and agree to be accountable for all aspects of the work.
* Joint corresponding authors.
The review process for this paper was fully handled by Christian Weber, Editor in Chief.
Publication History
Received: 27 June 2023
Accepted: 27 July 2023
Article published online:
25 August 2023
© 2023. Thieme. All rights reserved.
Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany
-
References
- 1 Lippi G, Sanchis-Gomar F, Cervellin G. Global epidemiology of atrial fibrillation: an increasing epidemic and public health challenge. Int J Stroke 2021; 16 (02) 217-221
- 2 Kornej J, Börschel CS, Benjamin EJ, Schnabel RB. Epidemiology of atrial fibrillation in the 21st century: novel methods and new insights. Circ Res 2020; 127 (01) 4-20
- 3 Hindricks G, Potpara T, Dagres N. et al; ESC Scientific Document Group. 2020 ESC guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS): The Task Force for the diagnosis and management of atrial fibrillation of the European Society of Cardiology (ESC) Developed with the special contribution of the European Heart Rhythm Association (EHRA) of the ESC. Eur Heart J 2021; 42 (05) 373-498
- 4 Chao TF, Joung B, Takahashi Y. et al. 2021 focused update consensus guidelines of the Asia Pacific Heart Rhythm Society on Stroke Prevention in Atrial Fibrillation: executive summary. Thromb Haemost 2022; 122 (01) 20-47
- 5 Romiti GF, Pastori D, Rivera-Caravaca JM. et al. Adherence to the 'Atrial Fibrillation Better Care' pathway in patients with atrial fibrillation: impact on clinical outcomes-a systematic review and meta-analysis of 285,000 patients. Thromb Haemost 2022; 122 (03) 406-414
- 6 De Caterina R, Husted S, Wallentin L. et al. 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 2013; 110 (06) 1087-1107
- 7 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
- 8 López-López JA, Sterne JAC, Thom HHZ. et al. Oral anticoagulants for prevention of stroke in atrial fibrillation: systematic review, network meta-analysis, and cost effectiveness analysis. BMJ 2017; 359: j5058
- 9 Ferreira-González I, Busse JW, Heels-Ansdell D. et al. Problems with use of composite end points in cardiovascular trials: systematic review of randomised controlled trials. BMJ 2007; 334 (7597): 786
- 10 Pocock SJ, Ariti CA, Collier TJ, Wang D. The win ratio: a new approach to the analysis of composite endpoints in clinical trials based on clinical priorities. Eur Heart J 2012; 33 (02) 176-182
- 11 Redfors B, Gregson J, Crowley A. et al. The win ratio approach for composite endpoints: practical guidance based on previous experience. Eur Heart J 2020; 41 (46) 4391-4399
- 12 Berwanger O, Pfeffer M, Claggett B. et al. Sacubitril/valsartan versus ramipril for patients with acute myocardial infarction: win-ratio analysis of the PARADISE-MI trial. Eur J Heart Fail 2022; 24 (10) 1918-1927
- 13 Sorajja P, Whisenant B, Hamid N. et al; TRILUMINATE Pivotal Investigators. Transcatheter repair for patients with tricuspid regurgitation. N Engl J Med 2023; 388 (20) 1833-1842
- 14 Pocock SJ, Ferreira JP, Collier TJ. et al. The win ratio method in heart failure trials: lessons learnt from EMPULSE. Eur J Heart Fail 2023; 25 (05) 632-641
- 15 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
- 16 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
- 17 Granger CB, Alexander JH, McMurray JJV. et al; ARISTOTLE Committees and Investigators. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med 2011; 365 (11) 981-992
- 18 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
- 19 Chowdhury KR, Michaud J, Yu OHY, Yin H, Azoulay L, Renoux C. Effectiveness and safety of apixaban versus rivaroxaban in patients with atrial fibrillation and type 2 diabetes mellitus. Thromb Haemost 2022; 122 (10) 1794-1803
- 20 Romiti GF, Proietti M, Bonini N. et al; GLORIA-AF Investigators. Clinical complexity domains, anticoagulation, and outcomes in patients with atrial fibrillation: a report from the GLORIA-AF registry phase II and III. Thromb Haemost 2022; 122 (12) 2030-2041
- 21 Krittayaphong R, Winijkul A, Methavigul K. et al; COOL-AF Investigators. Risk profiles and pattern of antithrombotic use in patients with non-valvular atrial fibrillation in Thailand: a multicenter study. BMC Cardiovasc Disord 2018; 18 (01) 174
- 22 Mehran R, Rao SV, Bhatt DL. et al. Standardized bleeding definitions for cardiovascular clinical trials: a consensus report from the Bleeding Academic Research Consortium. Circulation 2011; 123 (23) 2736-2747
- 23 Schulman S, Kearon C. Subcommittee on Control of Anticoagulation of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. J Thromb Haemost 2005; 3 (04) 692-694
- 24 Thygesen K, Alpert JS, Jaffe AS. et al; Executive Group on behalf of the Joint European Society of Cardiology (ESC)/American College of Cardiology (ACC)/American Heart Association (AHA)/World Heart Federation (WHF) Task Force for the Universal Definition of Myocardial Infarction. Fourth universal definition of myocardial infarction (2018). Circulation 2018; 138 (20) e618-e651
- 25 Hicks KA, Tcheng JE, Bozkurt B. et al; American College of Cardiology, American Heart Association. 2014 ACC/AHA key data elements and definitions for cardiovascular endpoint events in clinical trials: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Data Standards (Writing Committee to Develop Cardiovascular Endpoints Data Standards). Circulation 2015; 132 (04) 302-361
- 26 Lip GYH. The ABC pathway: an integrated approach to improve AF management. Nat Rev Cardiol 2017; 14 (11) 627-628
- 27 Cui Y, Huang B. WINS: The R WINS Package. Comprehensive R Archive Network (CRAN). Accessed April 27, 2023 at: https://cran.r-project.org/web/packages/WINS/index.html
- 28 Ho D, Imai K, King G, Stuart EA. MatchIt: nonparametric preprocessing for parametric causal inference. J Stat Softw 2011; 42 (08) 1-28
- 29 Finkelstein DM, Schoenfeld DA. Graphing the Win Ratio and its components over time. Stat Med 2019; 38 (01) 53-61
- 30 Oakes D. On the win-ratio statistic in clinical trials with multiple types of event. Biometrika 2016; 103 (03) 742-745
- 31 Cui Y, Dong G, Kuan PF, Huang B. Evidence synthesis analysis with prioritized benefit outcomes in oncology clinical trials. J Biopharm Stat 2023; 33 (03) 272-288
- 32 Carnicelli AP, Hong H, Connolly SJ. et al; COMBINE AF (A Collaboration Between Multiple Institutions to Better Investigate Non-Vitamin K Antagonist Oral Anticoagulant Use in Atrial Fibrillation) Investigators. Direct oral anticoagulants versus warfarin in patients with atrial fibrillation: patient-level network meta-analyses of randomized clinical trials with interaction testing by age and sex. Circulation 2022; 145 (04) 242-255
- 33 Deitelzweig S, Bergrath E, di Fusco M. et al. Real-world evidence comparing oral anticoagulants in non-valvular atrial fibrillation: a systematic review and network meta-analysis. Future Cardiol 2022; 18 (05) 393-405
- 34 Waranugraha Y, Rizal A, Syaban MFR, Faratisha IFD, Erwan NE, Yunita KC. 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. Egypt Heart J 2021; 73 (01) 70
- 35 Lip GYH, Keshishian A, Li X. et al. Effectiveness and safety of oral anticoagulants among nonvalvular atrial fibrillation patients. Stroke 2018; 49 (12) 2933-2944
- 36 Shen AY-J, 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 (04) 309-315
- 37 Wang K-L, Lip GYH, Lin S-J, Chiang C-E. Non-vitamin K antagonist oral anticoagulants for stroke prevention in asian patients with nonvalvular atrial fibrillation: meta-analysis. Stroke 2015; 46 (09) 2555-2561
- 38 Ambe K, Akita A, Wei J, Yoshii Y, Onishi M, Tohkin M. Comparison of efficacy and safety of direct oral anticoagulants and warfarin between patients in Asian and non-Asian regions: a systematic review and meta-regression analysis. Clin Pharmacol Ther 2023; 113 (06) 1240-1250
- 39 Xue Z, Zhang H. Non-vitamin K antagonist oral anticoagulants versus warfarin in Asians with atrial fibrillation: meta-analysis of randomized trials and real-world studies. Stroke 2019; 50 (10) 2819-2828
- 40 Chan Y-H, Lee H-F, Chao T-F. et al. 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 2019; 33 (06) 701-710
- 41 Romiti GF, Guo Y, Corica B, Proietti M, Zhang H, Lip GYH. mAF-App II trial investigators. Mobile health-technology-integrated care for atrial fibrillation: a win ratio analysis from the mAFA-II randomized clinical trial. Thromb Haemost 2023;
- 42 Zandecki L, Janion-Sadowska A, Kurzawski J. et al. Clinical presentation and 3-year outcomes of patients with acute coronary syndromes and non-obstructive coronary arteries on angiography. PLoS One 2020; 15 (06) e0234735
- 43 Prakash R, Horsfall M, Markwick A. et al. Prognostic impact of moderate or severe mitral regurgitation (MR) irrespective of concomitant comorbidities: a retrospective matched cohort study. BMJ Open 2014; 4 (07) e004984