Direct oral anticoagulants versus vitamin K antagonists in non-valvular atrial fibrillation (Q16-13B)

Direct oral anticoagulants versus vitamin K antagonists in non-valvular atrial fibrillation (Q16-13B)

Q16-13B

Overview

What is the issue?
  • Both vitamin K antagonists (mostly warfarin) and direct oral anticoagulants (DOAC: dabigatran, rivaroxaban, apixaban and edoxaban) are used for anticoagulation therapy for stroke prevention in patients with non-valvular atrial fibrillation (NVAF).
  • The use of DOACs is increasing due to fewer drug-drug and drug-food interactions and less need for monitoring.
What was the aim of the study?
  • This study, evaluated the safety and effectiveness (clinical benefits and harms) of DOACs in patients with NVAF compared to warfarin.
How was the study conducted?
  • We conducted a retrospective propensity score-matched, cohort study using administrative healthcare records on 255,851 patients newly prescribed anticoagulants, identified from seven Canadian provinces.
  • Patients with NVAF newly prescribed DOACs (dabigatran, rivaroxaban or apixaban) were matched to those newly prescribed warfarin.
  • The primary outcome was ischemic stroke or systemic embolization; secondary outcomes included major bleeding, all-cause mortality, myocardial infarction, and a composite outcome of all strokes, major bleeding and all-cause mortality.
  • Hazard Ratios (HR) and 95% confidence intervals (CI) were estimated and pooled across sites using meta-analysis.
What did the study find?
  • The study cohort included 128,273 new users of DOACs matched to 128,273 new users of warfarin, followed for an average of 2 years.
  • Comparing DOACs with warfarin showed:
    • A similar risk of ischemic stroke (HR 1.02; 95% CI: 0.87 to 1.20),
    • A lower risk of major bleeding (HR 0.81; 95% CI:0.69 to 0.97),
    • A lower risk of the composite outcome of all strokes, major bleeding and all-cause mortality (HR 0.81; 95% CI: 0.74 to 0.89) and
    • A lower risk of all-cause mortality (HR 0.81; 95% CI:0.78 to 0.8).
  • This large pan-Canadian study further demonstrates the ability of CNODES to analyze a large amount of anonymous patient data to contribute to the understanding of a drug’s risks and benefits after they have been marketed.
  • The results of this study, the most comprehensive of its kind in Canada, are consistent with previous research.
Implications
  • DOACs and warfarin provide similar effectiveness for ischemic stroke prevention for patients with NVAF in Canada.
  • However, DOACs carry a lower risk of major bleeding and all-cause mortality compared with warfarin.
Key messages
  • This large pan-Canadian study provides key data on the relative benefits and harms of DOACs as compared with warfarin for the treatment of patients with non-valvular atrial fibrillation.
  • These data can assist in informing physicians prescribing these medications along with other evidence and patient preferences.

Manuscripts

Sinyavskaya L, Matteau A, Johnson S, Durand M. Methodological challenges in assessment of current use of warfarin among patients with atrial fibrillation using dispensation data from administrative healthcare database. Pharmacoepidemiol Drug Saf. 2018 Sep;27(9):979-986.

Schnitzer ME, Platt RW, Durand M. A tutorial on dealing with time-varying eligibility for treatment: Comparing the risk of major bleeding with DOACs versus warfarin. Statistics in Medicine. 2020 Dec 20;39(29):4538-4550.

Douros A, Durand M, Doyle CM, Yoon S, Reynier P, Filion KB. Comparative effectiveness and safety of direct oral anticoagulants in patients with atrial fibrillation: A systematic review and meta-analysis of observational studies. Drug Safety 2019 Oct;42(10):1135-1148.

Sinyavskaya L, Renoux C, Durand M. Defining the duration of the dispensation of oral anticoagulants in administrative healthcare databases. Pharmacoepidemiol Drug Saf. 2022 Jan;31(1):105-109.

Sinyavskaya L, Schnitzer M, Renoux C, Guertin JR, Talbot D, Durand M. Evidence of the different associations of prognostic factors with censoring across treatment groups and impact on censoring weight model specification: the example of anticoagulation in atrial fibrillation. Am J Epidemiol. 2021 Dec 1;190(12):2671-2679.

Durand M, Schnitzer M, Pang M, Carney G, Eltonsy S, Filion KB, Fisher A, Jun M, Matteau A, Paterson JM, Quail J, Renoux C for the Canadian Network for Observational Drug Effect Studies (CNODES) Investigators. Effectiveness and safety among direct oral anticoagulants in nonvalvular atrial fibrillation: A multi-database cohort study with meta-analysis. Br J Clin Pharmacol. 2021 Jun;87(6):2589-2601.

Durand M, Schnitzer M, Pang M, Carney G, Eltonsy S, Filion KB, Fisher A, Jun M, Kuo IF, Renoux C, Paterson JM, Quail J and Matteau A for the Canadian Network for Observational Drug Effect Studies (CNODES) Investigators. Comparative Effectiveness and Safety of Direct Oral Anticoagulants compared to vitamin K antagonists in Non-Valvular Atrial Fibrillation: A Multi-center Observational Cohort Study. CMAJ Open 2020 Dec 18;8(4):E877-E886.

Presentations

Project Team

Methods Lead
Mireille Schnitzer PhD
Steering Committee Liaison
Kristian Filion PhD
Steering Committee Liaison
Pierre Ernst MD, MSc, FRCPC
Lead Analyst
Greg Carney BSc, PhD
Research Assistant
Site Investigator
Michael Paterson MSc
Ontario
Site Investigator
Jacqueline Quail PhD
Saskatchewan
Site Investigator
Alexis Matteau MD
Quebec
Site Investigator
Sherif Eltonsy MSc, PhD
Atlantic
Site Investigator
Hala Tamim PhD
Atlantic
Site Investigator
Anat Fisher MD, PhD
MarketScan
Site Investigator
I Fan Kuo ACPR, MSc, PharmD
Manitoba
Site Investigator
Christel Renoux PhD
CPRD
Site Investigator
Anat Fisher MD, PhD
British Columbia
Site Investigator
Min Jun PhD, MScMed(ClinEpi), MSc
Alberta
Analyst
Nianping Hu PhD
Saskatchewan
Analyst
Anjie Huang
Ontario
Analyst
Yan Wang MSc
Atlantic
Analyst
Greg Carney BSc, PhD
MarketScan
Analyst
Matthew Dahl BSc
Manitoba
Analyst
Rui Nie MSc
CPRD
Analyst
Greg Carney BSc, PhD
British Columbia
Analyst
Jianguo (James) Zhang MSc
Alberta
Analyst
Zhihai Ma
Alberta
Collaborator
Menglan Pang MSc