Amin Alpesh, Deitelzweig Steve, Jing Yonghua, Makenbaeva Dinara, Wiederkehr Daniel, Lin Jay, Graham John
Department of Medicine, Hospitalist Program, School of Medicine, University of California, UCIMC, 101 The City Drive South, Building 58, Room 110, ZC-4076H, Mail Code: 4076, Irvine, CA, 92868, USA,
J Thromb Thrombolysis. 2014;38(2):150-9. doi: 10.1007/s11239-013-1048-z.
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 (R(2) = 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.
在非瓣膜性心房颤动（NVAF）患者中，华法林的治疗范围内时间（TTR）存在很大差异。本研究的目的是评估在ARISTOTLE、ROCKET - AF和RE - LY试验中，华法林TTR的变化对NVAF患者中风/全身性栓塞（SSE）发生率和大出血发生率的影响。此外，还估计了在不同TTR值下使用新型口服抗凝剂（NOACs）而非华法林时临床终点的医疗成本差异。从已发表的文献和FDA文件中估计了接受华法林治疗的NVAF患者TTR值的四分位数范围以及相应的SSE和大出血事件发生率（%/患者 - 年=%/py）。通过回归分析评估SSE和大出血发生率与TTR值之间的关联，然后将计算出的回归系数用于分析在不同TTR值下使用每种NOAC与华法林（2010年成本；美国支付方视角）相关的医疗成本差异。华法林的TTR每增加10%，SSE发生率降低 - 0.32%/py（R² = 0.61；p < 0.001）。虽然大出血发生率随TTR增加而降低，但不显著（- 0.035%/py，p = 0.63）。随着华法林的TTR从30%增加到90%，阿哌沙班的估计医疗成本从 - 902美元降至 - 83美元，利伐沙班从 - 506美元增至 + 314美元，达比加群从 - 596美元增至 + 223美元。在NVAF患者中，华法林的TTR与SSE发生率之间存在显著负相关，但与大出血发生率无关。华法林TTR的变化影响了使用个体NOAC与华法林的经济比较。
