Circulation：阿派沙班在不同治疗时间窗内均优于华法林

　　欧美一项研究表明，在不同治疗时间窗内（TTR），阿派沙班在卒中或系统性栓塞、出血和死亡方面相对于华法林的优势基本相似。论文于5月2日在线发表于《循环》（Circulation）。

　　此项研究共纳入18021例房颤患者，并随机给予最短12个月的阿派沙班或华法林治疗。利用基于华法林经治患者真实TTR的线性混合模型估算中心平均TTR（cTTR），并利用包括患者特征在内的模型预测个体TTR（iTTR）。

　　结果显示，中位cTTR为66%（四分位界限为61%和71%）。在各cTTR和iTTR四分位，阿派沙班组卒中或系统性栓塞、大出血和死亡发生率均始终低于华法林组。在最低和最高cTTR四分位，卒中或系统性栓塞的危险比分别为0.73和0.88，死亡分别为0.91和0.91，大出血分别为0.50和0.75。在iTTR四分位可观察到相似结果。

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Efficacy and Safety of Apixaban Compared with Warfarin at Different Levels of Predicted INR Control for Stroke Prevention in Atrial Fibrillation.
BACKGROUND
In the ARISTOTLE trial apixaban compared with warfarin, reduced stroke and systemic embolism, major bleeding, and mortality. We evaluated treatment effects in relation to two predictions of time in therapeutic range (TTR).
METHODS AND RESULTS
The trial randomized 18,201 patients with atrial fibrillation to apixaban 5 mg twice daily or warfarin for at least 12 months. For each patient a center average TTR (cTTR) was estimated using a linear mixed model based on the real TTRs in its warfarin treated patients with a fixed effect for country and random effect for center. For each patient also an individual TTR (iTTR) was predicted using a linear mixed effects model including also patient characteristics. Median cTTR was 66% (interquartile limits 61% and 71%). Rates of stroke or systemic embolism, major bleeding and mortality were consistently lower with apixaban than warfarin across cTTR and iTTR quartiles. In the lowest and highest cTTR quartiles, hazard ratios (HR) for stroke or systemic embolism were respectively 0.73 (95% CI 0.53 - 1.00) and 0.88 (95% CI 0.57 - 1.35) (p interaction = 0.078), for mortality 0.91 (95% CI 0.74 - 1.13) and 0.91 (95% CI 0.71 - 1.16) (p interaction = 0.34) and for major bleeding 0.50 (95% CI 0.36 - 0.70) and 0.75 (95% CI 0.58 - 0.97) (p interaction = 0.095), respectively. Similar results were seen for quartiles of iTTR.
CONCLUSIONS
The benefits of apixaban compared with warfarin on stroke or systemic embolism, bleeding and mortality appear similar across the range of center and patient predicted quality of INR control.