Comparative effectiveness and safety of oral anticoagulants for atrial fibrillation: A retrospective cohort study
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Updated: Dec 23, 2025
The WATCHMAN Left Atrial Appendage Closure Device for Atrial Fibrillation
Published on: February 28, 2012
Anne Holbrook1,2, Richard Morrow3, Agnes Y Y Lee4
1Division of Clinical Pharmacology & Toxicology, McMaster University, Hamilton, ON, Canada. holbrook@mcmaster.ca.
Abstract:
Oral anticoagulants (OACs) are high-priority medications, frequently used with clinically important benefit and serious harm. Our objective was to compare the safety and effectiveness of direct-acting oral anticoagulants (DOACs) versus warfarin in a population where anticoagulation management and DOACs were readily available. A retrospective cohort study of all adults living in British Columbia with a diagnosis of atrial fibrillation and a first prescription for an OAC was conducted. Co-primary outcomes were ischemic stroke and systemic embolism, and major bleeding. Secondary outcomes included a net clinical outcome composite and analysis of discontinuation, switching, and key subgroups. We estimated the effects of treatment using time-to-event models with high-dimensional propensity score adjustment to control confounding. After adjustment for prescribing bias, a cohort (n = 20,113, 43.8% female, mean age 72.4 years) with a mean follow-up of 18.1 months showed that patients taking warfarin tended to be poorer, sicker, and less likely to have a cardiologist prescriber. Outcome event rates were not significantly different for DOACs compared to warfarin [adjusted rate ratio of 1.15 (0.91, 1.46) for systemic embolism, 0.94 (0.82, 1.08) for major bleeding, and 0.98 (0.90, 1.06) for net clinical outcome]. Only the effect of age on net clinical outcome met our strict criteria for predicting which group might be superior. Switch of drug class was associated with increased risk of events (p < 0.003). In this population, we found no difference in important clinical outcomes between warfarin and DOACs. Switching compared to not switching was associated with harm.
Insights
Direct-acting oral anticoagulants (DOACs) and warfarin showed similar safety and effectiveness for atrial fibrillation patients. Switching between these oral anticoagulants increased event risk, highlighting the importance of stable anticoagulation management.
Area of Science:
- Cardiology
- Pharmacology
- Public Health
Background:
- Oral anticoagulants (OACs) are crucial for preventing stroke in atrial fibrillation but carry risks.
- Direct-acting oral anticoagulants (DOACs) offer an alternative to warfarin, with varying real-world effectiveness data.
- Understanding comparative outcomes in accessible healthcare settings is vital for clinical decision-making.
Purpose of the Study:
- To compare the safety and effectiveness of DOACs versus warfarin in British Columbia adults with atrial fibrillation.
- To evaluate co-primary outcomes of ischemic stroke, systemic embolism, and major bleeding.
- To assess secondary outcomes including net clinical benefit and drug discontinuation/switching patterns.
Main Methods:
- Retrospective cohort study of 20,113 adults diagnosed with atrial fibrillation and initiating OAC therapy.
- Utilized time-to-event models with high-dimensional propensity score adjustment to control for confounding factors.
- Analyzed co-primary outcomes (ischemic stroke, systemic embolism, major bleeding) and secondary outcomes over an 18.1-month follow-up.
Main Results:
- No significant differences in event rates for systemic embolism, major bleeding, or net clinical outcome between DOACs and warfarin.
- Warfarin users were generally poorer, sicker, and less likely to have a cardiologist.
- Switching OAC drug class was associated with an increased risk of adverse events (p < 0.003).
Conclusions:
- In this population with readily available anticoagulation management, DOACs and warfarin demonstrated comparable safety and effectiveness.
- Switching between OACs is associated with increased harm and should be avoided.
- Further research may explore age-specific effects on net clinical outcomes.
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