Direct oral anticoagulants in non-valvular atrial fibrillation (Q16-13A)

Direct oral anticoagulants in non-valvular atrial fibrillation (Q16-13A)

Q16-13A

Overview

What is the issue?
  • Anticoagulation therapy is indicated to prevent systemic arterial embolization and ischemic stroke for patients with non-valvular atrial fibrillation (NVAF).
  • Direct oral anticoagulants (DOACs) are replacing warfarin in clinical use due to warfarin’s need for frequent monitoring and numerous food and drug interactions.
  • No large, head-to-head randomized controlled trials (RCTs) have directly compared different DOACs for efficacy or safety.
What was the aim of the study?
  • This study evaluated the effectiveness and safety (clinical benefits and harms) of different DOACs in NVAF.
How was the study conducted?
  • We conducted retrospective, propensity score-matched, cohort studies using administrative healthcare data on 227,579 patients with NVAF who were new users of oral anticoagulants, identified from seven Canadian provinces and two international databases.
  • Dabigatran, rivaroxaban, and apixaban were compared pairwise.
  • 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 death.
  • Hazard ratios (HR) and 95% confidence intervals (CI) were estimated and pooled across sites using meta-analysis
What did the study find?
  • Rivaroxaban, compared with dabigatran, did not find a significant difference in the risk of ischemic stroke (HR 1.11; 95% CI: 0.93 to 1.32) but found an increased risk of major bleeding (HR 1.26; 95% CI: 1.09 to 1.46).
  • Apixaban, compared with dabigatran, did not find significant differences in the risks of ischemic stroke (HR 0.91; 95% CI: 0.74 to 1.12) and major bleeding (HR 0.89; 95% CI: 0.75 to 1.05).
  • Apixaban, compared with rivaroxaban, showed reduced risks of ischemic stroke (HR 0.85; 95% CI: 0.74 to 0.99) and major bleeding (HR 0.61; 95% CI: 0.53 to 0.70).
Implications
  • Apixaban is associated with lower risks of ischemic stroke and major bleeding, compared with rivaroxaban, and similar risks of these outcomes when compared with dabigatran.
  • Rivaroxaban is associated with an increased risk of major bleeding and a similar risk of ischemic stroke, when compared with dabigatran.
Key messages
  • This is one of the largest observational studies to date including patients initiating apixaban, rivaroxaban and dabigatran for stroke prevention in non-valvular atrial fibrillation.
  • Our findings of lower risks of both bleeding and stroke with apixaban compared with rivaroxaban contribute to the understanding of benefits and risks of DOACs after marketing in the Canadian setting.

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