AIMS: Apixaban was superior to aspirin for the prevention of stroke or systemic embolism in participants with subclinical atrial fibrillation (SCAF) in the Apixaban for the Reduction of Thromboembolism in Patients With Device-Detected Subclinical Atrial Fibrillation trial. This was especially true for those with CHA2DS2-VASc score > 4. Understanding the cost-effectiveness of treating SCAF is important for decision-makers. METHODS AND RESULTS: Canadian, UK, German, and US direct healthcare costs [in 2023 US dollars (USD)] were applied to hospitalized events (including strokes and bleeds) and study drugs for all participants with a CHA2DS2-VASc score > 4 to determine the mean cost per participant during the trial (mean follow-up 3.5 years). A daily cost of $0.63, $0.11, $2.26, and $6.06 for apixaban in Canada, the UK, Germany, and the USA was used. If in-trial results were not cost-saving (below $0), the prospective plan was to perform a lifetime cost-effectiveness analysis using a Markov model and a willingness-to-pay of 50 000 USD per quality-adjusted life year (QALY). After considering the cost of study medication and clinical events over 3.5 years, apixaban was dominant (cost-saving and more effective) in Canada (-$2301) and the UK (-$902) but cost more in Germany and the USA ($600 and $1990, respectively). Over a lifetime, treatment with apixaban produced a net gain of 0.107 QALYs, but with costs in both Germany ($2623 more) and the USA ($9110 more), yielding an incremental cost-effectiveness ratio of $24 514 per QALY for Germany and $85 140 for the USA. CONCLUSION: In patients with SCAF and a CHA2DS2-VASc score > 4, apixaban is cost saving in Canada and the UK and cost-effective in Germany. Apixaban was not cost-effective in the USA under the base cost assumption but would be cost-effective at a daily cost of $4.35 and cost saving at $3.59.

Arrhytmia Unit Hospital Universitario La Luz Madrid Spain

Breda and WCN Amphia Ziekenhuis Utrecht Netherlands

Canadian VIGOUR Centre University of Alberta Edmonton AB Canada

Cardiology Clinical Academic Group Molecular and Clinical Sciences Institute City St George's University of London London UK

Clinical Cardiovascular Research Center University of Rochester Rochester NY USA

Department of Cardiac Sciences University of Calgary Calgary AB Canada

Department of Cardiology Aarhus University Aarhus Denmark

Department of Cardiology Cardiovascular Research Institute Basel Basel Switzerland

Department of Cardiology Goethe University University Hospital Frankfurt Germany

Department of Cardiology Herlev Gentofte Hospital Copenhagen Denmark

Department of Cardiology J W Goethe University Frankfurt am Main Germany

Department of Cardiology Karolinska Institutet Karolinska University Hospital Stockholm Sweden

Department of Cardiology Liverpool Heart and Chest Hospital Liverpool UK

Department of Cardiology Oslo University Hospital Ulleval Oslo Norway

Department of Cardiology The Institute for Clinical and Experimental Medicine Praha 4 Czech Republic

Department of Cardiology University Hospital Basel Basel Switzerland

Department of Clinical Medicine Aarhus University Aarhus Denmark

Department of Medicine Medical University of South Carolina Charleston SC USA

Division of Cardiology University of Ottawa Heart Institute Ottawa Ontario Canada

Duke Clinical Research Institute Duke University Durham NC USA

Heart and Vascular Center Semmelweis University Budapest Hungary

Heart Vascular and Neurology Theme Karolinska University Hospital Stockholm Sweden

Institute of Clinical Medicine University of Oslo Oslo Norway

Population Health Research Institute McMaster University 237 Barton Street East Hamilton Ontario L8L2X2 Canada

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