Online citations, reference lists, and bibliographies.
← Back to Search

Comparative Efficacy And Safety Of Warfarin Care Bundles And Novel Oral Anticoagulants In Patients With Atrial Fibrillation: A Systematic Review And Network Meta-analysis

Siok Shen Ng, Nai Ming Lai, S. Nathisuwan, N. Jahan, P. Dilokthornsakul, Khachen Kongpakwattana, W. Hollingworth, N. Chaiyakunapruk
Published 2020 · Medicine

Cite This
Download PDF
Analyze on Scholarcy
Share
Warfarin care bundles (e.g. genotype-guided warfarin dosing, patient’s self-testing [PST] or patient’s self-management [PSM] and left atrial appendage closure) are based on the concept of combining several interventions to improve anticoagulation care. NOACs are also introduced for stroke prevention in atrial fibrillation (SPAF). However, these interventions have not been compared in head-to-head trials yet. We did a network meta-analysis based on a systematic review of randomized controlled trials comparing anticoagulant interventions for SPAF. Studies comparing these interventions in adults, whether administered alone or as care bundles were included in the analyses. The primary efficacy outcome was stroke and the primary safety outcome was major bleeding. Thirty-seven studies, involving 100,142 patients were assessed. Compared to usual care, PSM significantly reduced the risk of stroke (risk ratio [RR] 0.24, 95% CI 0.08–0.68). For major bleeding, edoxaban 60 mg (0.80, 0.71–0.90), edoxaban 30 mg (0.48, 0.42–0.56), and dabigatran 110 mg (0.81, 0.71–0.94) significantly reduced the risk of major bleeding compared with usual warfarin care. Cluster rank plot incorporating stroke and major bleeding outcomes indicates that some warfarin care bundles perform as well as NOACs. Both interventions are therefore viable options to be considered for SPAF. Additional studies including head-to-head trials and cost-effectiveness evaluation are still warranted.
This paper references
Using Care Bundles to Improve Health Care Quality
R. Resar (2012)
10.1093/AGEING/AFL129
A randomised controlled trial of warfarin versus aspirin for stroke prevention in octogenarians with atrial fibrillation (WASPO).
Amar Rash (2007)
10.1016/j.jacc.2014.04.029
Prospective randomized evaluation of the Watchman Left Atrial Appendage Closure device in patients with atrial fibrillation versus long-term warfarin therapy: the PREVAIL trial.
D. Holmes (2014)
10.1001/archinte.154.13.1449
Risk factors for stroke and efficacy of antithrombotic therapy in atrial fibrillation. Analysis of pooled data from five randomized controlled trials.
(1994)
10.1007/978-94-007-0753-5_103411
A Randomized Trial
S. V. Desai (2013)
10.1016/0002-8223(94)91977-1
The New England Journal of Medicine
J. (2012)
Low-dose aspirin for prevention of stroke in low-risk patients with atrial fibrillation: Japan Atrial Fibrillation
H Sato (1988)
10.1055/S-2007-996423
State-of-the-art patient self-management for control of oral anticoagulation.
U. Taborski (1999)
10.1160/TH10-07-0451
Safety of edoxaban, an oral factor Xa inhibitor, in Asian patients with non-valvular atrial fibrillation.
N. Chung (2011)
10.1001/ARCHINTE.158.14.1513
Fixed minidose warfarin and aspirin alone and in combination vs adjusted-dose warfarin for stroke prevention in atrial fibrillation: Second Copenhagen Atrial Fibrillation, Aspirin, and Anticoagulation Study.
A. L. Gulløv (1998)
10.1016/S0019-4832(12)60030-3
Apixaban versus warfarin in patients with atrial fibrillation.
N. Deshpande (2012)
10.1007/s00392-005-0199-0
Self-Management of oral Anticoagulation in nonvalvular Atrial Fibrillation (SMAAF study)
P. H. Völler (2005)
Secondary prevention in non-rheumatic atrial fibrillation after transient ischaemic attack or minor stroke
M. Ceravolo (1993)
10.1590/S0066-782X2010005000140
Varfarina ou Aspirina na prevenção de fenômenos embólicos na valvopatia mitral com fibrilação atrial
P. L. Lavítola (2010)
the management of atrial fibrillation (CG180), https://www
National Insitute for Health (2014)
10.1016/j.jacc.2014.01.069
The prognostic value of bleeding academic research consortium (BARC)-defined bleeding complications in ST-segment elevation myocardial infarction: a comparison with the TIMI (Thrombolysis In Myocardial Infarction), GUSTO (Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occlu
W. J. Kikkert (2014)
a randomised cross-over comparison
Cromheecke (2000)
10.1016/j.jclinepi.2010.03.016
Graphical methods and numerical summaries for presenting results from multiple-treatment meta-analysis: an overview and tutorial.
G. Salanti (2011)
10.1136/bmj.j5058
Oral anticoagulants for prevention of stroke in atrial fibrillation: systematic review, network meta-analysis, and cost effectiveness analysis
J. López-López (2017)
10.1056/NEJMoa1002617
Effect of home testing of international normalized ratio on clinical events.
D. Matchar (2010)
10.1038/clpt.2013.190
Cost‐Effectiveness of Pharmacogenetics‐Guided Warfarin Therapy vs. Alternative Anticoagulation in Atrial Fibrillation
J. Pink (2014)
10.1002/sim.3767
Checking consistency in mixed treatment comparison meta-analysis.
S. Dias (2010)
10.1016/J.JEMERMED.2014.02.015
A Pharmacogenetic versus a Clinical Algorithm for Warfarin Dosing
W. G. Sungar (2014)
10.3121/CMR.3.3.137
A prospective, randomized pilot trial of model-based warfarin dose initiation using CYP2C9 genotype and clinical data.
Michael A Hillman (2005)
10.1007/s11239-006-5580-y
Worldwide Management of Oral Anticoagulant Therapy: the ISAM Study
V. Pengo (2006)
10.1136/bmj.327.7414.557
Measuring inconsistency in meta-analyses
J. Higgins (2003)
Warfarin versus aspirin for prevention of thromboembolism in atrial fibrillation : stroke prevention in atrial fibrillation II study. Commentary
H. White (1994)
systematic review, network meta-analysis, and cost effectiveness analysis
Lopez-Lopez (2020)
10.1016/S0140-6736(94)91577-6
Warfarin versus aspirin for prevention of thromboembolism in atrial fibrillation: Stroke Prevention in Atrial Fibrillation II Study
Stroke Prevention in Atrial Fibrillation Investigators (1994)
10.1016/J.AMJCARD.2007.06.034
Dabigatran with or without concomitant aspirin compared with warfarin alone in patients with nonvalvular atrial fibrillation (PETRO Study).
M. Ezekowitz (2007)
10.1111/j.1365-2141.2004.05074.x
The value of education and self‐monitoring in the management of warfarin therapy in older patients with unstable control of anticoagulation
T. Khan (2004)
10.1161/CIRCULATIONAHA.110.009449
Standardized Bleeding Definitions for Cardiovascular Clinical Trials: A Consensus Report From the Bleeding Academic Research Consortium
R. Mehran (2011)
10.1161/01.STR.0000198839.61112.EE
Low-dose aspirin for prevention of stroke in low-risk patients with atrial fibrillation: Japan Atrial Fibrillation Stroke Trial.
H. Sato (2006)
3
Balshem (2011)
10.1016/j.jclinepi.2010.07.015
GRADE guidelines: 3. Rating the quality of evidence.
Howard Balshem (2011)
10.1056/NEJMoa1310907
Edoxaban versus warfarin in patients with atrial fibrillation.
R. Giugliano (2013)
10.1592/phco.31.12.1232
Dabigatran Etexilate in Clinical Practice: Confronting Challenges to Improve Safety and Effectiveness
Michael P. Gulseth (2011)
10.1038/sj.clpt.6100316
CYP2C9 Genotype‐guided Warfarin Prescribing Enhances the Efficacy and Safety of Anticoagulation: A Prospective Randomized Controlled Study
Y. Caraco (2008)
10.1056/nejmc0909962
Dabigatran versus warfarin in patients with atrial fibrillation.
J. Worthington (2009)
10.1016/j.amjmed.2009.11.025
Underuse of oral anticoagulants in atrial fibrillation: a systematic review.
I. Ogilvie (2010)
an overview and tutorial
G. Salanti (2011)
10.1177/1708538113490423
Prevention of stroke and systemic embolism with rivaroxaban compared with warfarin in Chinese patients with atrial fibrillation
L. Mao (2014)
10.1017/S1121189X00000452
What is a randomised controlled trial?
A. Cipriani (2009)
confronting challenges to improve safety and effectiveness
Gulseth (2011)
10.1111/joor.12540
Network meta-analysis.
A. De Laat (2017)
10.1056/nejm197210192871623
The randomized clinical trial.
E. M. Glaser (1972)
10.1097/GIM.0b013e31820ad77d
A randomized controlled trial of genotype-based Coumadin initiation
J. K. Burmester (2011)
The Efficacy and Safety of Rivaroxaban as an Alternative to Warfarin for the Prevention of Thromboembolism in Patients with Atrial Fibrillation
R. I. Shosha (2017)
10.2147/CPAA.S105165
Systematic review and network meta-analysis of stroke prevention treatments in patients with atrial fibrillation
A. Tawfik (2016)
10.1136/bmj.d5928
The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials
J. P. Higgins (2011)
10.1002/j.1875-9114.2012.01116
Impact of a Pharmacist‐Led Warfarin Self‐Management Program on Quality of Life and Anticoagulation Control: A Randomized Trial
L. Verret (2012)
10.1056/NEJMC1112233#SA3
Rivaroxaban versus warfarin in nonvalvular atrial fibrillation.
R. Rosenstein (2011)
10.1136/bmj.g5630
A GRADE Working Group approach for rating the quality of treatment effect estimates from network meta-analysis
M. Puhan (2014)
10.1016/0735-1097(91)90585-W
Canadian Atrial Fibrillation Anticoagulation (CAFA) Study.
S. Connolly (1991)
10.7326/0003-4819-133-9-200011070-00010
A Multicomponent Intervention To Prevent Major Bleeding Complications in Older Patients Receiving Warfarin
R. Beyth (2000)
CYP 2 C 9 Genotype-guided Warfarin Prescribing Enhances the Efficacy and Safety of Anticoagulation : A Prospective Randomized Controlled Study
Y. Caraco (2011)
10.1016/0197-2456(86)90046-2
Meta-analysis in clinical trials.
R. Dersimonian (1986)
10.2217/pgs.13.145
Impact of genotype-guided dosing on anticoagulation visits for adults starting warfarin: a randomized controlled trial.
D. Jonas (2013)
positive effects on quality of life
A. P. Gadisseur (2004)
A GRADE Working Group approach for rating the quality of treatment effect estimates from network metaanalysis. BMJ (Clinical research ed
Puhan (2014)
10.1590/S0066-782X2010005000140
Warfarin or aspirin in embolism prevention in patients with mitral valvulopathy and atrial fibrillation.
P. L. Lavítola (2010)
10.1016/S0140-6736(94)92620-4
Stroke Prevention in Atrial Fibrillation II Study.
S. Connolly (1994)
10.1055/S-0037-1613888
A prospective controlled trial comparing weekly self-testing and self-dosing with the standard management of patients on stable oral anticoagulation.
H. Watzke (2000)
10.1177/0193945910394380
Systematic Review
F. Nabavi (2012)
Safety of edoxaban, an oral factor Xa inhibitor, in Asian patients with nonvalvular atrial fibrillation. Thrombosis and haemostasis
N Chung (2011)
10.1253/CIRCJ.CJ-11-1140
Randomized, multicenter, warfarin-controlled phase II study of edoxaban in Japanese patients with non-valvular atrial fibrillation.
T. Yamashita (2012)
10.1001/jamaneurol.2017.2161
Rivaroxaban vs Warfarin Sodium in the Ultra-Early Period After Atrial Fibrillation–Related Mild Ischemic Stroke: A Randomized Clinical Trial
Keun‐Sik Hong (2017)
10.1056/NEJM199011293232201
The effect of low-dose warfarin on the risk of stroke in patients with nonrheumatic atrial fibrillation.
D. Singer (1990)
10.1056/NEJMoa0905561
Dabigatran versus warfarin in patients with atrial fibrillation.
S. Connolly (2009)
combining direct and indirect evidence
D. M. Caldwell (2005)
10.5414/CP201996
Warfarin compared with aspirin for older Chinese patients with stable coronary heart diseases and atrial fibrillation complications.
Xinbing Liu (2014)
10.1016/S0140-6736(00)02470-3
Oral anticoagulation self-management and management by a specialist anticoagulation clinic: a randomised cross-over comparison
M. Cromheecke (2000)
10.2147/TCRM.S84210
New oral anticoagulants: their advantages and disadvantages compared with vitamin K antagonists in the prevention and treatment of patients with thromboembolic events
Y. Mekaj (2015)
10.1136/bmjopen-2015-007758
Is self-monitoring an effective option for people receiving long-term vitamin K antagonist therapy? A systematic review and economic evaluation
P. Sharma (2015)
Japan Atrial Fibrillation Stroke Trial
Sato (2006)
the ISAM study
V. Pengo (2006)
10.1016/S0140-6736(89)91200-2
PLACEBO-CONTROLLED, RANDOMISED TRIAL OF WARFARIN AND ASPIRIN FOR PREVENTION OF THROMBOEMBOLIC COMPLICATIONS IN CHRONIC ATRIAL FIBRILLATION: The Copenhagen AFASAK Study
P. Petersen (1989)
10.1253/CIRCJ.CJ-12-0454
Rivaroxaban vs. warfarin in Japanese patients with atrial fibrillation – the J-ROCKET AF study –.
M. Hori (2012)
10.7326/M14-2385
The PRISMA Extension Statement for Reporting of Systematic Reviews Incorporating Network Meta-analyses of Health Care Interventions: Checklist and Explanations
B. Hutton (2015)
10.1093/eurheartj/ehu161
Prospective validation of the Bleeding Academic Research Consortium classification in the all-comer PRODIGY trial.
P. Vranckx (2014)
checklist and explanations
Hutton (2015)
10.1016/j.ijcard.2013.08.054
Is home warfarin self-management effective? Results of the randomised Self-Management of Anticoagulation Research Trial.
R. Dignan (2013)
10.1056/NEJMoa1311386
A randomized trial of genotype-guided dosing of warfarin.
M. Pirmohamed (2013)
10.1371/journal.pone.0076654
Graphical Tools for Network Meta-Analysis in STATA
A. Chaimani (2013)
10.1161/JAHA.116.003206
Comparative Effectiveness of Interventions for Stroke Prevention in Atrial Fibrillation: A Network Meta‐Analysis
L. Tereshchenko (2016)
the PREVAIL trial
Holmes (2014)
Measuring inconsistency in meta-analyses. BMJ (Clinical research ed
J. P. Higgins (2003)
10.1016/S0140-6736(74)92478-7
Letter: Psychosomatic medicine.
Z. J. Lipowski (1974)
10.3760/CMA.J.ISSN.0366-6999.2012.24.007
Anticoagulation therapy in Chinese patients with non-valvular atrial fibrillation: a prospective, multi-center, randomized, controlled study.
K. Chen (2012)
10.1016/J.SPINEE.2010.07.215
A Prospective, Multi-center, Randomized Controlled Study to Compare a Low Swell Formulation of a PEG Hydrogel Spinal Sealant as an Adjunct to Sutured Dural Repair with Common Dural Sealing Methods
D. Chou (2010)
10.7326/0003-4819-142-1-200501040-00006
Comparing Self-Management of Oral Anticoagulant Therapy with Clinic Management
Brbara Menndez-Jndula (2005)
10.1002/SIM.1875
Combination of direct and indirect evidence in mixed treatment comparisons.
G. Lu (2004)
10.1001/jama.2014.15192
Percutaneous left atrial appendage closure vs warfarin for atrial fibrillation: a randomized clinical trial.
V. Reddy (2014)
10.1111/j.1538-7836.2004.00659.x
Patient self‐management of oral anticoagulant care vs. management by specialized anticoagulation clinics: positive effects on quality of life
A. P. A. Gadisseur (2004)
10.1161/01.CIR.84.2.527
Stroke Prevention in Atrial Fibrillation Study: Final Results
Lippincott Williams Wilkins (1991)
A randomised controlled trial of warfarin versus aspirin for stroke prevention in octogenarians with atrial fibrillation (WASPO). Age and ageing
A Rash (2007)
10.1056/NEJMoa1007432
Apixaban in patients with atrial fibrillation.
S. Connolly (2011)
10.1016/S0140-6736(06)68845-4
Clopidogrel plus aspirin versus oral anticoagulation for atrial fibrillation in the Atrial fibrillation Clopidogrel Trial with Irbesartan for prevention of Vascular Events (ACTIVE W): a randomised controlled trial.
S. Connolly (2006)
10.1016/S0140-6736(07)61233-1
Warfarin versus aspirin for stroke prevention in an elderly community population with atrial fibrillation (the Birmingham Atrial Fibrillation Treatment of the Aged Study, BAFTA): a randomised controlled trial
J. Mant (2007)
10.1160/TH10-01-0066
Randomised, parallel-group, multicentre, multinational phase 2 study comparing edoxaban, an oral factor Xa inhibitor, with warfarin for stroke prevention in patients with atrial fibrillation.
J. Weitz (2010)
10.1007/S00268-005-1100-Z
Randomized controlled trial.
A. Sanabria (2005)
10.1136/bmj.331.7521.897
Simultaneous comparison of multiple treatments: combining direct and indirect evidence
D. Caldwell (2005)
10.1056/NEJMc1112233
Rivaroxaban versus warfarin in nonvalvular atrial fibrillation.
S. Pearson (2011)
a prospective randomized controlled study
Y. Caraco (2008)
10.1253/CIRCJ.CJ-10-1183
Safety and efficacy of the oral direct factor xa inhibitor apixaban in Japanese patients with non-valvular atrial fibrillation. -The ARISTOTLE-J study-.
S. Ogawa (2011)
10.1136/bmjopen-2013-004301
Systematic review and network meta-analysis comparing antithrombotic agents for the prevention of stroke and major bleeding in patients with atrial fibrillation
Chris Cameron (2014)
The Efficacy and Safety of Rivaroxaban as an Alternative to Warfarin for the Prevention of Thromboembolism in Patients with Atrial Fibrillation
R. I. Shosa (2017)



Semantic Scholar Logo Some data provided by SemanticScholar