Abstract
Warfarin’s time-in-therapeutic range (TTR) is highly variable among patients with nonvalvular atrial fibrillation (NVAF). The objective of this study was to estimate the impact of variations in wafarin’s TTR on rates of stroke/systemic embolism (SSE) and major bleedings among NVAF patients in the ARISTOTLE, ROCKET-AF, and RE-LY trials. Additionally, differences in medical costs for clinical endpoints when novel oral anticoagulants (NOACs) were used instead of warfarin at different TTR values were estimated. Quartile ranges of TTR values and corresponding event rates (%/patient − year = %/py) of SSE and major bleedings among NVAF patients treated with warfarin were estimated from published literature and FDA documents. The associations of SSE and major bleeding rates with TTR values were evaluated by regression analysis and then the calculated regression coefficients were used in analysis of medical cost differences associated with use of each NOAC versus warfarin (2010 costs; US payer perspective) at different TTRs. Each 10 % increase in warfarin’s TTR correlated with a −0.32 %/py decrease in SSE rate (R2 = 0.61; p < 0.001). Although, the rate of major bleedings decreased as TTR increased, it was not significant (−0.035 %/py, p = 0.63). As warfarin’s TTR increased from 30 to 90 % the estimated medical cost decreased from −$902 to −$83 for apixaban, from −$506 to +$314 for rivaroxaban, and from −$596 to +$223 for dabigatran. Among NVAF patients there is a significant negative correlation between warfarin’s TTR and SSE rate, but not major bleedings. The variations in warfarin’s TTR impacted the economic comparison of use of individual NOACs versus warfarin.
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Acknowledgments
This research was supported by Bristol-Myers Squibb and Pfizer. We would like to acknowledge M. Lingohr-Smith from Novosys Health for the editorial support and review of this manuscript. This support was funded by Bristol-Myers Squibb and Pfizer.
Conflict of interest
Y. Jing, D. Makenbaeva and J. Graham are employees of Bristol-Myers Squibb and own stock in the company. D. Wiederkehr is an employee of Pfizer and owns stock in the company. J. Lin is an employee of Novosys Health, which has received financial support from Bristol-Myers Squibb and Pfizer in connection with conducting this study and development of this manuscript. A. Amin and S. Deitelzweig are paid consultants for Novosys Health in connection with conducting this study.
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Amin, A., Deitelzweig, S., Jing, Y. et al. Estimation of the impact of warfarin’s time-in-therapeutic range on stroke and major bleeding rates and its influence on the medical cost avoidance associated with novel oral anticoagulant use-learnings from ARISTOTLE, ROCKET-AF, and RE-LY trials. J Thromb Thrombolysis 38, 150–159 (2014). https://doi.org/10.1007/s11239-013-1048-z
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DOI: https://doi.org/10.1007/s11239-013-1048-z