Electronic Thesis and Dissertation Repository

Thesis Format

Integrated Article

Degree

Master of Science

Program

Epidemiology and Biostatistics

Supervisor

Sarma, Sisira

2nd Supervisor

Schwarz, Ute

Co-Supervisor

Abstract

This study assessed cost-effectiveness of pharmacogenomics (PGx)-based warfarin, apixaban and rivaroxaban compared to standard warfarin therapy for atrial fibrillation (AF) patients in Canada. A decision-analytic Markov model was developed to compare lifetime costs and quality-adjusted life years (QALYs) from the public healthcare payer perspective. The parameters applied in the model were derived from published literature and some costs from the IC/ES databases. The results were summarized in terms of the incremental cost-effectiveness ratio (ICER). Compared to standard warfarin, PGx-based warfarin care had an ICER of 17,727/QALY and apixaban had an ICER of $64,853/QALY gained. Apixaban dominated rivaroxaban. The probabilistic sensitivity analysis showed that apixaban, rivaroxaban, PGx-based warfarin and standard warfarin were cost-effective at some willingness-to-pay (WTP) thresholds. Specifically, PGxbased warfarin therapy had a higher probability of being cost-effective than apixaban (51.5% vs 14.1%) at a WTP threshold of $50,000/QALY. At a WTP threshold of $150,000/QALY, apixaban had a higher probability of being cost-effective than PGxbased warfarin (70.1% vs 5.7%). We found that apixaban offers the best balance between efficacy and safety and has a high probability of being cost-effective for AF patients in Canada at a WTP threshold of $150,000/QALY.

Summary for Lay Audience

Atrial fibrillation (AF) is a condition defined by the presence of irregular rapid heartbeats. Patients with AF have been commonly treated by a blood thinner (anticoagulant) called warfarin to reduce the risk of stroke. However, rigorous monitoring of the blood thinning effect is required to avoid adverse events such as stroke and/or bleeding from inappropriate warfarin dosing. The trial and error approach of current clinical practice for warfarin dosing involves routine blood tests and poses an increased risk of adverse events during the initial dose adjustment period. Warfarin-related adverse events entail a substantial burden on patients’ health and the healthcare system. In comparison, pharmacogenomic-based (PGx) warfarin therapy adjusts the drug dose according to the inherent genetic differences of AF patients and has been shown to reduce risk of adverse events. A new class of drugs for AF therapy are called direct oral anticoagulants (DOACs), and offer several advantages over warfarin. For example, apixaban and rivaroxaban are now funded by the Ontario Ministry of Health and longterm care (MOHLTC). DOACs have a predictable pharmacokinetic and dose response, do not require continuous monitoring, have increased effectiveness in reducing the risk of stroke and embolism and are associated with decreased risk of bleeding. However, PGxbased warfarin entails an upfront cost for genetic testing, while the medication cost for DOACs is more than twice than that of warfarin. This cost-effectiveness analysis compares the lifetime costs and benefits incurred under each treatment strategy from the MOHLTC perspective. We found that PGx-based warfarin care as well as apixaban and rivaroxaban improved the health of AF patients by reducing the risk of ischemic strokes and intracranial bleeding as compared to standard warfarin, yet these alternative treatments also increased lifetime costs when compared to standard warfarin. PGx-based warfarin led to a small increase in QALYs and large increase in costs. Among the DOACs, apixaban treatment resulted in the highest health benefit and dominated rivaroxaban. The results of this study were sensitive to treatment effectiveness and should be interpreted with caution.

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