Electronic Thesis and Dissertation Repository

Thesis Format

Integrated Article


Master of Science


Epidemiology and Biostatistics


Sarma, Sisira


Atrial fibrillation patients are at high risk of ischemic strokes, which can be drastically reduced using oral anticoagulants (OACs). Warfarin has been the standard OAC for this population but its effectiveness rests on consistent monitoring with the potential for severe bleeding events. Newer OACs, like rivaroxaban and apixaban, address these drawbacks but have a comparatively higher upfront cost. Uncertainty remains over which OAC is cost-saving from a health care system perspective. Using a retrospective cohort study design and inverse probability weighting regression adjustment estimators, one-year health care costs among patients treated with warfarin, rivaroxaban, and apixaban were compared. Compared to warfarin, rivaroxaban and apixaban treatments are cost-saving with per-patient one-year total health care savings at $2,436 and $1,764, respectively. This was driven by significant cost savings in hospitalization, emergency department visits, and physician visits for rivaroxaban and apixaban compared to warfarin. These results can influence provincial OAC reimbursement policies.

Summary for Lay Audience

Atrial fibrillation is a common form of irregular heartbeat that leads to five times increase in the risk of stroke, but anticoagulation therapy greatly reduces this risk. The standard oral anticoagulant (OAC), warfarin, has a small effective range, outside of which there is high variability of effects and an increased risk of severe side effects like serious bleeding events. This has resulted in OAC underuse, exposing atrial fibrillation patients to higher stroke risks. Newer OACs, like rivaroxaban and apixaban, have been developed to address warfarin’s drawbacks with predictable and stable effects but have a higher upfront cost.

It is uncertain which OAC is cost-saving for the health care system. Some studies from the United States have indicated that both rivaroxaban and apixaban are cheaper than warfarin but disagree on which of the newer OACs is the cheapest option, and the size of the cost-savings. To date, no study has compared health care costs associated with treatment of warfarin, rivaroxaban, and apixaban in the Canadian context.

This thesis assessed differences in one-year health care costs of patients treated with rivaroxaban or apixaban compared to patients treated with warfarin. The study cohort consists of Ontario residents aged 66 and older who were diagnosed with atrial fibrillation between 2012-2017 and prescribed one of the OACs. The cost analysis adjusted the different OAC groups across demographic and clinical characteristics. Overall and component-specific health care costs (i.e. drug, hospitalization, emergency department (ED), and physician) were compared to determine the most cost-saving OAC option.

Results showed that rivaroxaban and apixaban were associated with statistically significant one-year overall cost savings compared to warfarin at $2,436 and $1,764 in per-patient savings, respectively. These savings were due to reductions in hospitalization, ED, and physician costs, outweighing the significantly higher drug costs compared to warfarin. Additional analysis showed that rivaroxaban use was associated with cost savings particularly for women and patients at high-risk of bleeding events. These findings could influence OAC reimbursement policy for the Ontario Ministry of Health and Long-term Care which currently favours warfarin over rivaroxaban and apixaban as the first treatment option.

Creative Commons License

Creative Commons Attribution-Noncommercial 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-Share Alike 4.0 License.