Interventions and Strategies to Improve Oral Anticoagulant Use in Patients with Atrial Fibrillation: A Systematic Review of Systematic Reviews

  • Siok Shen Ng
  • Nai Ming Lai
  • Surakit Nathisuwan
  • Nathorn Chaiyakunapruk
Systematic Review
  • 53 Downloads

Abstract

Introduction

Anticoagulation therapy is the fundamental approach for stroke prevention in atrial fibrillation (AF) patients. Numerous systematic reviews comparing anticoagulation strategies have been published. We aim to summarize the efficacy and safety evidence of these strategies in AF patients from previously published systematic reviews.

Methods

We searched PubMed, EMBASE and Cochrane library from inception to Feb 24th, 2017, to identify systematic reviews and meta-analyses of randomized controlled trials that assessed interventions or strategies to improve oral anticoagulant use in AF patients.

Results

Thirty-four systematic reviews were eligible for inclusion but only 11 were included in the qualitative analyses, corresponding to 40 unique meta-analyses, as the remaining systematic reviews had overlapping primary studies. There was insufficient evidence to support the efficacy of genotype-guided dosing and pharmacist-managed anticoagulation clinics for stroke prevention in AF patients. Conversely, patient’s self-management and novel oral anticoagulants (NOACs), in general were superior to warfarin for preventing stroke and reducing mortality. All interventions showed comparable risk of major bleeding with warfarin.

Conclusion

Findings from this overview support the superiority of NOACs and patient’s self-management for preventing stroke in AF patients. However, uncertainties remain on the benefits of genotype-guided dosing and pharmacist-managed anticoagulation clinics due to poor quality evidence, and future research is warranted.

Notes

Acknowledgements

We are grateful for the help of Dr. Shaun Lee Wen Huey from School of Pharmacy, Monash University Malaysia for his invaluable advice and support in the preparation of this manuscript.

Compliance with Ethical Standards

Funding

This research did not receive any specific Grant from funding agencies in the public, commercial, or not-for-profit sectors.

Conflict of interest

Siok Shen Ng, Nai Ming Lai, Surakit Nathisuwan and Nathorn Chaiyakunapruk have no conflict of interest to declare.

Author Contributions

All authors have made substantial contributions to the research design, or the acquisition, analysis, or interpretation of data; and to drafting the paper or revising it critically; and that all authors have approved the submitted version.

Supplementary material

40261_2018_641_MOESM1_ESM.pdf (956 kb)
Supplementary material 1 (PDF 957 kb)

References

  1. 1.
    Wolf PA, Abbott RD, Kannel WB. Atrial fibrillation as an independent risk factor for stroke: the Framingham Study. Stroke. 1991;22(8):983–8.CrossRefPubMedGoogle Scholar
  2. 2.
    Lip GY. Stroke and bleeding risk assessment in atrial fibrillation: when, how, and why? Eur Heart J. 2013;34(14):1041–9.  https://doi.org/10.1093/eurheartj/ehs435.CrossRefPubMedGoogle Scholar
  3. 3.
    Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Ann Intern Med. 2009;151(4):264–9.CrossRefPubMedGoogle Scholar
  4. 4.
    Keisu M, Andersson TB. Drug-induced liver injury in humans: the case of ximelagatran. Handb Exp Pharmacol. 2010;196:407–18.  https://doi.org/10.1007/978-3-642-00663-0_13.CrossRefGoogle Scholar
  5. 5.
    Apostolakis S, Lip GY. Novel oral anticoagulants: focus on the direct factor Xa inhibitor darexaban. Exp Opin Investig Drugs. 2012;21(7):1057–64.  https://doi.org/10.1517/13543784.2012.689286.CrossRefGoogle Scholar
  6. 6.
    Bafeta A, Trinquart L, Seror R, Ravaud P. Analysis of the systematic reviews process in reports of network meta-analyses: methodological systematic review. BMJ (Clinical research ed). 2013;347:f3675.  https://doi.org/10.1136/bmj.f3675.PubMedCentralGoogle Scholar
  7. 7.
    Whiting P, Savovic J, Higgins JP, Caldwell DM, Reeves BC, Shea B, et al. ROBIS: a new tool to assess risk of bias in systematic reviews was developed. J Clin Epidemiol. 2016;69:225–34.  https://doi.org/10.1016/j.jclinepi.2015.06.005.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Schulman S, Kearon C. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. J Thromb Haemost JTH. 2005;3(4):692–4.  https://doi.org/10.1111/j.1538-7836.2005.01204.x.CrossRefPubMedGoogle Scholar
  9. 9.
    Belley-Cote EP, Hanif H, D’Aragon F, Eikelboom JW, Anderson JL, Borgman M, et al. Genotype-guided versus standard vitamin K antagonist dosing algorithms in patients initiating anticoagulation. A systematic review and meta-analysis. Thromb Haemost. 2015;114(4):768–77.  https://doi.org/10.1160/th15-01-0071.CrossRefPubMedGoogle Scholar
  10. 10.
    Bloom BJ, Filion KB, Atallah R, Eisenberg MJ. Meta-analysis of randomized controlled trials on the risk of bleeding with dabigatran. Am J Cardiol. 2014;113(6):1066–74.  https://doi.org/10.1016/j.amjcard.2013.11.049.CrossRefPubMedGoogle Scholar
  11. 11.
    Dentali F, Riva N, Crowther M, Turpie AG, Lip GY, Ageno W. Efficacy and safety of the novel oral anticoagulants in atrial fibrillation: a systematic review and meta-analysis of the literature. Circulation. 2012;126(20):2381–91.  https://doi.org/10.1161/circulationaha.112.115410.CrossRefPubMedGoogle Scholar
  12. 12.
    Garg J, Chaudhary R, Krishnamoorthy P, Palaniswamy C, Shah N, Bozorgnia B, et al. Safety and efficacy of oral factor-Xa inhibitors versus vitamin K antagonist in patients with non-valvular atrial fibrillation: meta-analysis of phase II and III randomized controlled trials. Int J Cardiol. 2016;218:235–9.  https://doi.org/10.1016/j.ijcard.2016.05.059.CrossRefPubMedGoogle Scholar
  13. 13.
    Heneghan CJ, Garcia-Alamino JM, Spencer EA, Ward AM, Perera R, Bankhead C et al. Self-monitoring and self-management of oral anticoagulation. Cochrane Database Syst Rev. 2016;7.  https://doi.org/10.1002/14651858.cd003839.pub3.
  14. 14.
    Katsanos AH, Mavridis D, Parissis J, Deftereos S, Frogoudaki A, Vrettou AR, et al. Novel oral anticoagulants for the secondary prevention of cerebral ischemia: a network meta-analysis. Ther Adv Neurol Disord. 2016;9(5):359–68.  https://doi.org/10.1177/1756285616659411.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Morilla MA, Tumulak CD, Gulay CB, Dioquino CP, Morales DD. A meta-analysis on the efficacy of dabigatran versus warfarin among patients with atrial fibrillation. Philipp J Intern Med. 2012;50(4):1–4.Google Scholar
  16. 16.
    Ruff CT, Giugliano RP, Braunwald E, Hoffman EB, Deenadayalu N, Ezekowitz MD, 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 (London, England). 2014;383(9921):955–62.  https://doi.org/10.1016/s0140-6736(13)62343-0.CrossRefGoogle Scholar
  17. 17.
    Sadlon AH, Tsakiris DA. Direct oral anticoagulants in the elderly: systematic review and meta-analysis of evidence, current and future directions. Swiss Med Wkly. 2016;146:w14356.  https://doi.org/10.4414/smw.2016.14356.PubMedGoogle Scholar
  18. 18.
    Wells PS, Brown A, Jaffey J, McGahan L, Poon MC, Cimon K. Safety and effectiveness of point-of-care monitoring devices in patients on oral anticoagulant therapy: a meta-analysis. Open Med Peer Rev Indep Open Access J. 2007;1(3):e131–46.Google Scholar
  19. 19.
    Zhou S, Sheng XY, Xiang Q, Wang ZN, Zhou Y, Cui YM. Comparing the effectiveness of pharmacist-managed warfarin anticoagulation with other models: a systematic review and meta-analysis. J Clin Pharm Ther. 2016;41(6):602–11.  https://doi.org/10.1111/jcpt.12438.CrossRefPubMedGoogle Scholar
  20. 20.
    Jia B, Lynn HS, Rong F, Zhang W. Meta-analysis of efficacy and safety of the new anticoagulants versus warfarin in patients with atrial fibrillation. J Cardiovasc Pharmacol. 2014;64(4):368–74.  https://doi.org/10.1097/fjc.0000000000000129.CrossRefPubMedGoogle Scholar
  21. 21.
    Saposnik G, Hill MD, O’Donnell M, Fang J, Hachinski V, Kapral MK. Variables associated with 7-day, 30-day, and 1-year fatality after ischemic stroke. Stroke. 2008;39(8):2318–24.  https://doi.org/10.1161/strokeaha.107.510362.CrossRefPubMedGoogle Scholar
  22. 22.
    Steger C, Pratter A, Martinek-Bregel M, Avanzini M, Valentin A, Slany J, et al. Stroke patients with atrial fibrillation have a worse prognosis than patients without: data from the Austrian Stroke registry. Eur Heart J. 2004;25(19):1734–40.  https://doi.org/10.1016/j.ehj.2004.06.030.CrossRefPubMedGoogle Scholar
  23. 23.
    Providencia R, Grove EL, Husted S, Barra S, Boveda S, Morais J. A meta-analysis of phase III randomized controlled trials with novel oral anticoagulants in atrial fibrillation: comparisons between direct thrombin inhibitors vs. factor Xa inhibitors and different dosing regimens. Thromb Res. 2014;134(6):1253–64.  https://doi.org/10.1016/j.thromres.2014.10.002.CrossRefPubMedGoogle Scholar
  24. 24.
    Patel MR, Mahaffey KW, Garg J, Pan G, Singer DE, Hacke W, et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med. 2011;365(10):883–91.  https://doi.org/10.1056/NEJMoa1009638.CrossRefPubMedGoogle Scholar
  25. 25.
    Granger CB, Alexander JH, McMurray JJ, Lopes RD, Hylek EM, Hanna M, et al. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2011;365(11):981–92.  https://doi.org/10.1056/NEJMoa1107039.CrossRefPubMedGoogle Scholar
  26. 26.
    Pirmohamed M, Burnside G, Eriksson N, Jorgensen AL, Toh CH, Nicholson T, et al. A randomized trial of genotype-guided dosing of warfarin. N Engl J Med. 2013;369(24):2294–303.  https://doi.org/10.1056/NEJMoa1311386.CrossRefPubMedGoogle Scholar
  27. 27.
    Sharma P, Scotland G, Cruickshank M, Tassie E, Fraser C, Burton C, et al. Is self-monitoring an effective option for people receiving long-term vitamin K antagonist therapy? A systematic review and economic evaluation. BMJ Open. 2015;5(6):e007758.  https://doi.org/10.1136/bmjopen-2015-007758.CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    National Institute for Health and Care Excellence. Atrial fibrillation: management (CG180) [Internet]. NICE, London 2014. https://www.nice.org.uk/guidance/cg180.
  29. 29.
    White HD, Gruber M, Feyzi J, Kaatz S, Tse HF, Husted S, et al. Comparison of outcomes among patients randomized to warfarin therapy according to anticoagulant control: results from SPORTIF III and V. Arch Intern Med. 2007;167(3):239–45.  https://doi.org/10.1001/archinte.167.3.239.CrossRefPubMedGoogle Scholar
  30. 30.
    Stergiopoulos K, Brown DL. Genotype-guided vs clinical dosing of warfarin and its analogues: meta-analysis of randomized clinical trials. JAMA Intern Med. 2014;174(8):1330–8.  https://doi.org/10.1001/jamainternmed.2014.2368.CrossRefPubMedGoogle Scholar
  31. 31.
    Connolly SJ, Ezekowitz MD, Yusuf S, Eikelboom J, Oldgren J, Parekh A, et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009;361(12):1139–51.  https://doi.org/10.1056/NEJMoa0905561.CrossRefPubMedGoogle Scholar
  32. 32.
    Giugliano RP, Ruff CT, Braunwald E, Murphy SA, Wiviott SD, Halperin JL, et al. Edoxaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2013;369(22):2093–104.  https://doi.org/10.1056/NEJMoa1310907.CrossRefPubMedGoogle Scholar
  33. 33.
    Trusler M. Well-managed warfarin is superior to NOACs. Can Fam Phys. 2015;61(1):23–4.Google Scholar
  34. 34.
    Raschi E, Bianchin M, Ageno W, De Ponti R, De Ponti F. Risk–benefit profile of direct-acting oral anticoagulants in established therapeutic indications: an overview of systematic reviews and observational studies. Drug Saf. 2016;39(12):1175–87.  https://doi.org/10.1007/s40264-016-0464-3.CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Moher D, Shamseer L, Clarke M, Ghersi D, Liberati A, Petticrew M, et al. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement. Syst Rev. 2015;4:1.  https://doi.org/10.1186/2046-4053-4-1.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.School of PharmacyMonash University MalaysiaBandar SunwayMalaysia
  2. 2.Department of PharmacyHospital MelakaMelakaMalaysia
  3. 3.School of MedicineTaylor’s University MalaysiaSubang JayaMalaysia
  4. 4.Clinical Pharmacy Division, Department of Pharmacy, Faculty of PharmacyMahidol UniversityBangkokThailand
  5. 5.Department of Pharmacy Practice, Faculty of Pharmaceutical Sciences, Center of Pharmaceutical Outcomes Research (CPOR)Naresuan UniversityPhitsanulokThailand
  6. 6.School of PharmacyUniversity of WisconsinMadisonUSA
  7. 7.Asian Centre for Evidence Synthesis in Population, Implementation and Clinical Outcomes (PICO), Health and Well-Being Cluster, Global Asia in the 21st Century (GA21) Platform, Monash University MalaysiaBandar SunwayMalaysia

Personalised recommendations