Safety of direct oral anticoagulants in patients with venous thromboembolism (Q14-02)

Safety of direct oral anticoagulants in patients with venous thromboembolism (Q14-02)

Safety of direct oral anticoagulants in patients with venous thromboembolism (Q14-02)

Q14-02

Overview

What is the issue?
  • Direct oral anticoagulants (DOACs) are used in the treatment of venous thromboembolism (VTE). They offer advantages over the use of warfarin, with no need for regular monitoring and dose adjustment.
  • Clinical trials have shown that DOACs have a comparable efficacy to warfarin, however their safety in a real-world setting remains uncertain.
What was the aim of the study?
  • The aim was to evaluate the safety (major bleeding and all-cause mortality) of DOAC (dabigatran, apixaban or rivaroxaban) use compared with warfarin use for the treatment of VTE.
How was the study conducted?
  • We undertook a retrospective, propensity score-matched cohort study using health records from 5 Canadian provinces (Alberta, Manitoba, Ontario, Quebec and Saskatchewan) and the US IBM MarketScan® database.
  • The study cohort included 59,525 adult patients with a new diagnosis of VTE and a prescription for a DOAC or warfarin within 30 days of the diagnosis.
  • The outcomes were major bleeding requiring hospital admission or emergency department visit and all-cause mortality within 90 days of treatment initiation.
  • Hazard ratios (HR) and 95% confidence intervals (CI) were estimated and pooled across sites using meta-analysis.
What did the study find?
  • Among patients with VTE, treatment with DOACs compared to warfarin was not associated with an increased risk of major bleeding (HR 0.92; 95% CI: 0.82 to 1.03) or all-cause mortality (HR 0.99; 95% CI: 0.84 to 1.16).
  • Results were consistent for patients with and without chronic kidney disease, across all age groups, and for men and women.
  • These findings provide reassurance as to the risk of major bleeding and all-cause mortality with DOACs in a real-world setting.
Implications
  • These findings provide evidence for the safety of DOACs in the treatment of VTE in a real-world setting.
  • Physicians may not need to consider the risk of major bleeding when prescribing a DOAC instead of warfarin.
Key Messages
  • Compared to warfarin, treatment of newly-diagnosed VTE with a DOAC was not associated with an increased risk of major bleeding or all-cause mortality.

Manuscripts

Jun M, Lix LM, Durand M, Dahl M, Paterson JM, Dormuth CR, Ernst P, Yao S, Renoux C, Tamim H, Wu C, Mahmud SM, Hemmelgarn BR, For the Canadian Network for Observational Drug Effect Studies (CNODES) Investigators. Comparative safety of direct oral anticoagulants and warfarin in venous thromboembolism: multicentre, population-based, observational study. BMJ. 2017 Oct 17;359:j4323.

Presentations

Project Team

Methods Lead
Lisa Lix BSHEc, MSc, PhD, P Stat
Manitoba
Content Expert
Cynthia Wu
Steering Committee Liaison
Pierre Ernst MD, MSc, FRCPC
Lead Analyst
Matthew Dahl BSc
Site Investigator
Shenzhen Yao MSc
Saskatchewan
Site Investigator
Alexis Matteau MD
Quebec
Site Investigator
Madeleine Durand MD, MSc, FRCPC
Quebec
Site Investigator
Michael Paterson MSc
Ontario
Site Investigator
Hala Tamim PhD
Atlantic
Site Investigator
Colin R. Dormuth ScD
MarketScan
Site Investigator
Salah Mahmud MD MSc PhD FRCP(c)
Manitoba
Site Investigator
Christel Renoux PhD
CPRD
Site Investigator
Min Jun PhD, MScMed(ClinEpi), MSc
Alberta
Analyst
Nianping Hu PhD
Saskatchewan
Analyst
Wenbin Li
Saskatchewan
Analyst
Thierry Ducruet
Quebec
Analyst
Fangyun Wu MSc
Ontario
Analyst
Yan Wang MSc
Atlantic
Analyst
Greg Carney BSc, PhD
MarketScan
Analyst
Matthew Dahl BSc
Manitoba
Analyst
Jianguo (James) Zhang MSc
Alberta
Analyst
Zhihai Ma
Alberta