Cost-effectiveness of apixaban vs aspirin for the reduction of thrombo-embolism in high-risk patients with device-detected atrial fibrillation: insights from the ARTESiA trial

Background The Apixaban for the Reduction of Thrombo-Embolism in Patients with Subclinical Atrial Fibrillation (ARTESiA) trial demonstrated that apixaban, compared to aspirin, prevented stroke or systemic embolism, with the largest effect among patients with a CHA₂DS₂-VASc score >4. We hypothesize that apixaban in patients with a CHA₂DS₂-VASc score >4 will be cost-effective due to cost savings from stroke prevention. Methods Using healthcare perspectives specific to Canada, the UK, Germany and the US, direct healthcare costs (in 2023 USD) were applied to hospitalized events and study drugs used by all CHA₂DS₂-VASc score >4 participants. The daily cost of apixaban was $0.63, $0.11, $2.26, and $6.06 for Canada, the UK, Germany and the US. We determined the mean cost per participant for the full duration of the trial (mean follow-up of 3.5 years). If in-trial results were not cost-saving (below $0), we performed a lifetime cost-effectiveness analysis using a Markov model and assumed a willingness to pay of 50,000 USD per Quality Adjust Life-Year (QALY). The Markov model consisted of five states (Alive, Dead, Discontinued, Rankin 0-2 Post-Stroke and Rankin 3-5 Post-Stroke) with a 3-month cycle length. While alive, participants experienced one of eight events (no event, non-fatal myocardial infarction, non-fatal ischemic stroke, fatal ischemic stroke, non-fatal hemorrhagic stroke, fatal hemorrhagic stroke, major gastrointestinal/ genitourinary bleed, or death) based on data from the ARTESiA trial. Costs and utilities were obtained from national tariffs and published literature. Results During the trial, the cost of events was lower in the apixaban arm in all countries. After taking into consideration the cost of study medication, apixaban was cost saving (dominant strategy) in Canada (-$2301) and the UK (-$902) but cost more in Germany and the US ($600 and $1990 respectively) and thus modelling was required for these two countries. Over a lifetime, apixaban results in 4.995 QALYs compared to 4.888 QALYs for patients taking aspirin; a difference of 0.107 QALYs. During this period participants taking apixaban accrued higher costs than those taking aspirin in both Germany ($2623 more) and the US ($9110 more). This resulted in an incremental cost effectiveness ratio of $24,514 for Germany and $85,140 per QALY for the US. One-way sensitivity analyses of drug and event costs and of event probabilities used in our model identified the cost of apixaban as the only factor impacting cost-effectiveness. In the US, this sensitivity analysis indicates a daily cost of $4.35 is required to achieve a willingness-to-pay of $50,000/QALY. Conclusion In patients with device detected atrial fibrillation with CHA₂DS₂-VASc score >4, apixaban is cost-saving in Canada and the UK and cost-effective in Germany. Apixaban is not cost-effective in the US at current prices.